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Application form Research Project Proposal

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NSTIP Application form Research Project Proposal

NSTIP Application form Research Project Proposal

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  • 1. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 1 of 25 Sohda, T, Momose, Y, Meguro, K, Kawamatsu, Y, Sugiyama, Y, Ikeda, H, Arzneim-Forsch, 1990, 40, 37.
  • 2. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 2 of 25 CNPSTI RE-D1: APPLICATION FORM - RESEARCH PROJECT PROPOSAL ITEM DESCRIPTION PLAN The First Five - Year Science, Technology and Innovation Plan PROGRAM Strategic Technologies SUB-PROGRAM / TECHNOLOGY AREA1 Biotechnology TRACK Medical and Health Research SUB-TRACK Diabetics PROJECT TITLE (ENGLISH) COMPUTRER BASED MOLECULAR MODELING, DRUG DESIGN, SYNTHESIS AND ANTIDIABETIC EVALUATION OF NEW POTENTIAL ANTIDIABETIC AGENTS PROJECT TITLE (ARABIC) ‫تصميم‬‫وتقييم‬ ‫وتشييد‬ ‫الحبسوبية‬ ‫الجزيئية‬ ‫النمذجة‬ ‫على‬ ‫مبنى‬ ‫دوائى‬. PRINCIPAL INVESTIGATOR (ENGLISH) Dr. Noman Shah P. INVESTIGATOR (ARABIC ) ‫د‬.‫نعمبن‬ INSTITUTION Umm Al-Qura University FOR OFFICIAL USE ONLY SUBMITTED FOR THE DEADLINE OF 30th of MARCH 30th of SEPTEMBER DATE RECIEVED PROJECT CODE 1 Applicants are advised to visit the following link for more information about technology areas, tracks and sub- tracks http://www.kacst.edu.sa/en/research/Pages/default.aspx.
  • 3. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 3 of 25 CNPSTI RE -D1-1: PROJECT INFORMATION ITEM DESCRIPTION PROJECT TITLE COMPUTRER BASED MOLECULAR MODELING, DRUG DESIGN, SYNTHESIS AND ANTIDIABETIC EVALUATION OF NEW POTENTIAL ANTIDIABETIC MEDICINE TECHNOLOGY AREA Biotechnology TRACK Medical and Health Research SUB-TRACK Diabetics PROJECT TYPE (BASIC, APPLIED, DEVELOPMENT) Development PROPOSED TOTAL BUDGET (MAX. TWO MILLIONS SR ) Two millions Saudi Riyals ESTIMATED DURATION ( MAX. 24 MONTHS) 24 Months PROPOSED STARTING DATE January 2013 Month / Year SENIOR PERSONNEL PROJECT TEAM No. Name Role Area of Specialization 1 Dr. Noman Shah P I Organic-Medicinal Chemistry 2 Dr. Hassan Wadood CO- I Organic-Medicinal Chemistry 3 Dr. Ahmed CO- I Biochemistry OTHER PERSONNEL 6 Postdoctoral Associate 7 Ph.D. Student 8 Will be recruited M.S. Student 9 Will be recruited Technician 10 Will be recruited Project Manager 11 Will be recruited Other: Research Assistants CONSULTANT* 12 Pr. Bill Gates Country: US 13 Pr. Stephon Hawking Country: US *NOTE: a letter of approval from the consultant/s should be attached with the application. KEYWORDS (MAX. 4) 1. Antidiabetic Type 2 agents 2. 3. 4. IS THIS PROJECT BEING SUBMITTED TO ANY OTHER FUNDING INSTITUTION? No Yes, please specify 1. 2. 3.
  • 4. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 4 of 25 - Summary (English): Type 2 diabetes is a common chronic disease, characterized by a progressive rise in blood glucose and worsening insulin resistance that is a major cause of morbidity and mortality. Currently, it is estimated that more than 16 million people suffering from diabetes live in the Eastern Mediterranean Region. This staggering figure is expected to extend to almost 43 million by the year 2025. In case no imperative action is undertaken, the proportion of people living with diabetes is predicted to jump from 366 million in 2011 to 552 million by 2030, according to new estimates. This corresponds to almost three new cases every ten seconds or about ten million per year. Nearly 183 million people are unconscious that they have diabetes according to International Diabetes Federation (IDF) estimates. - Summary (Arabic): ‫تاندو‬ ‫انجهىجىس‬ ‫إرتفاع‬ ‫يزض‬(ٌ‫انسكز‬)‫انُىع‬ ٍ‫ي‬2‫عوا‬ ٍ‫يوشي‬ ‫يوزض‬ ‫هوى‬‫تود‬ ‫تارتفواع‬ ‫َتًُوش‬‫يسوتىي‬ ٍ‫فو‬ ٍ‫رَج‬ ‫وانىفاج‬ ‫نهًزض‬ ٍ‫ُس‬ ‫ر‬ ‫سثة‬ ‫هى‬ ٌ‫انذ‬ ٍُ‫االَسىن‬ ‫يقاويح‬ ‫وتفاقى‬ ‫اندو‬ ٍ‫ف‬ ‫انسكز‬.ٌ‫ا‬ ً‫انو‬ ‫ا‬‫ا‬‫اانُو‬ ‫انتقودَزاخ‬ ‫وتشُز‬‫أكثوز‬ ٍ‫ي‬61ٌ‫َعُشى‬ ٌ‫انسكز‬ ٍ‫ي‬ ٌ‫َعاَى‬ ‫عخص‬ ٌ‫يهُى‬‫يُففوح‬ ٍ‫فو‬‫اووسو‬ ‫انشوز‬.‫انًوذهم‬ ‫انوزقى‬ ‫وهوذا‬ٌ‫أ‬ ‫انًتىقو‬ ٍ‫يو‬ ‫َزتف‬ً‫إن‬ٍ‫ي‬ ‫َقزب‬ ‫يا‬34‫تحهى‬ ‫َسًح‬ ٌ‫يهُى‬‫ل‬‫عاو‬2222.‫عدو‬ ‫اال‬ ٍ‫وف‬‫إجوزا‬ ٌ‫أ‬ ‫اتخوا‬‫تقفوش‬ ٌ‫أ‬ ‫انًتىقو‬ ٍ‫فًو‬ ٌ‫َعُشى‬ ٍَ‫انذ‬ ٌ‫انسكا‬ ‫َسثح‬‫ي‬ٌ‫انسوكز‬ ‫يوزض‬ٍ‫يو‬411ٌ‫يهُوى‬ٍ‫فو‬2266ٍ‫اتو‬222ٌ‫يهُوى‬‫عواو‬ ‫تحهوىل‬2242 ‫نتقدَزاخ‬ ‫وفقا‬‫جدَدج‬.‫ي‬ ‫َتىافق‬ ‫وهذا‬‫ثالث‬ ٍ‫ي‬ ‫َقزب‬ ‫يا‬‫جدَدج‬ ‫إصاتح‬ ‫ااالخ‬‫كوم‬ٌ‫ثوىا‬ ‫عشوز‬‫أو‬ٍُ‫يالَو‬ ‫عشوزج‬ ‫َحوى‬ ‫سُىَا‬.‫هُاك‬ ٌ‫وأ‬ٍ‫ي‬ ‫َقزب‬ ‫يا‬684ٌ‫َعهًى‬ ‫ال‬ ‫َسًح‬ ٌ‫يهُى‬‫ندَهى‬ ٌ‫تأ‬ٌ‫انسكز‬ ‫يزض‬‫اال‬ ‫نتقدَزاخ‬ ‫وفقا‬ٍ‫انفودران‬ ‫تحا‬ ٌ‫نهسكز‬ ٍ‫اندون‬(IDF). 1. INTRODUCTION Diabetes is one of the oldest known diseases. An Egyptian manuscript from 1550 BCE asserts the sentence “the passing of too much urine” [1]. The great Indian physician Sushruta (6th century BCE) differentiated the disease and classified it as Medhumeha [2]. The ancient Indians investigated for diabetes by contemplating if ants were tempted by a person's urine, and designate the ailment "sweet urine disease" (Madhumeha). Presently, diabetes is the world’s restless propagating chronic disease. A UN Resolution 61/225 was voted on December 2006 recognizing diabetes as a major health crisis encountered by all nations of the world. The Resolution baptized 14 November each year as the United Nations World Diabetes. The world Health Organization recently warned that type II diabetes has become worldly pandemic [3]. In
  • 5. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 5 of 25 case no imperative action is taken, the proportion of people living with diabetes is predicted to increment from 366 million in 2011 to 552 million by 2030, according to new estimates. This corresponds to almost three new cases every ten seconds or about ten million per year. Nearly 183 million people are unconscious that they have diabetes according to International Diabetes Federation (IDF) estimates. Diabetes mellitus is a chronic metabolic disease that originates when a person has high blood sugar, either because the pancreatic cells do not produce enough insulin (because the pancreas does not longer produce or not produce insulin in sufficient amounts), or when the body cannot respond effectively to the insulin that is produced. Insulin is a hormone generated by the pancreas that grants the uptake of glucose from the blood by cells and converts it into energy. Consequently, glucose present in food and consumed by diabetic people cannot be converted into energy. Instead of being turned into energy the glucose stays in the blood. Glucose gets entrapped in the bloodstream and spills into the urine when the muscles and organs are starved for energy. For this reason blood glucose levels are higher in diabetic people. The blood’s high sugar content damages the cells of many organs it flows through. If the levels are very high, they can cause coma or death. Defection in producing insulin, or of insulin to act properly, or both, generates increased glucose (sugar) levels in the blood (hyperglycaemia). This is accompanied by long-term damage to the body and deterioration of various organs and tissues. Over time, diabetes engenders annihilation or invalidation throughout the body. It disturbs the blood vessels and the heart, multiplying the risk of heart disease or stroke by up to four times. Such complications are lethal to two-thirds of people who have diabetes. By the time they are diagnosed, many people have already deteriorated the blood vessels in their eyes and 90 percent of them have deterioration after 15 years with the illness; As a result, almost 40,000 cases of blindness are engendered each year, making diabetes one of the leading cause of adult-onset blindness [4]. When time passes, the high levels of sugar in the blood damage the millions of tiny filtering units within each kidney. This eventually leads to a major complication: kidney failure [5]. Amputations eventuate 10 times more frequently in people with diabetes than in sane people, and the illness also invalidates the immune system, making people more receptive to serious infection.
  • 6. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 6 of 25 There are three main types of diabetes. First, type 1 diabetes accounts for about 10% of all diabetes. It results from autoimmune mediated destruction of insulin-secreting β-cells of the pancreas [6] and solicits daily insulin administration, also referred to as insulin- dependent diabetes mellitus, IDDM for short, and juvenile diabetes.). Type 1 diabetes amass alarming chemical substances in their blood from the burning of fat unless controlled with daily injections of insulin. This can lead to a situation known as ketoacidosis. This situation is potentially life threatening if not treated. Second, type 2, or the most common form of diabetes that affects 85-90% of all diabetic people [7]. It is mainly generated by insulin resistance, a condition in which cells fail to use insulin properly, formerly referred to as non-insulin-dependent diabetes mellitus, NIDDM for short, and adult-onset diabetes progressed to require injected insulin. This can develop to type 1, or latent autoimmune diabetes of adults (or LADA or "type 1.5" diabetes) [8]. Type 2 diabetes can remain undetected for many years and the diagnosis is often made from combined complications or fortuitously through an abnormal blood or urine glucose analysis. It is often, but not always, in relation with obesity, which itself can cause insulin resistance and induce elevated blood glucose levels. Third gestational diabetes (GDM) [9] is another type of diabetes when pregnant women, who have never had diabetes before, are subjected to high blood glucose levels during pregnancy which may lead to the development of type 2 DM. It is associated with complications in the period immediately before and after birth. Other causes of diabetes include congenital, which is due to genetic defects of insulin secretion, cystic fibrosis- related, steroid induced by high doses of glucocorticoids, and several forms of monogenic. Diabetes without adequate treatments can cause numerous complications. Disastrous complications comprise diabetic ketoacidosis, or nonketotic hyperosmolar coma. Grave long-term complications include cardiovascular disease, chronic renal failure, retinal damage. According to estimations of 2010, there are 285 million people diabetes with type 2 representing about 90% of the cases. [10] Other types of diabetes as pre-diabetes illustrate a condition that takes place when a person's blood glucose levels are more elevated than normal but not high enough for a diagnosis of type 2 diabetes. Many people destined to develop type 2 diabetes spend
  • 7. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 7 of 25 many years in a state of pre-diabetes which has been designated by "largest healthcare epidemic." [11]. The cause of diabetes relies on the type. Type 1 diabetes is partly inherited and then triggered by certain infections, with some confirmation implicating Coxsackie B4 virus [12]. Type 2 diabetes is due primarily to lifestyle factors and genetics [13]. There are other causes of diabetes [14] including genetic defects of β-cell Function, genetic defects in insulin processing or insulin action, exocrine pancreatic defects, infections or due to some drugs. While there is not yet a cure for diabetes, it can be controlled. The main goal of all treatment is to control blood sugar levels, but the method varies depending on the type of diabetes a person has. The sustained, high plasma glucose levels results in a gradual progression of a number of complications, including neuropathy, nephropathy, retinopathy, and premature athereosclerosis [15]. Proper glycemic control is, most likely, necessary for the control of diabetic complications in type 2 diabetes [16]. However, current therapies to reduce plasma glucose levels have inherent problems including compliance, ineffectiveness, and occurrence of hypoglycemic episodes with insulin and sulphonyl urea. Accordingly, there is a need for more effective, orally administered agents, particularly ones that act as insulin sensitizing antidiabetic agents in peripheral tissue in order to normalize both glucose and insulin levels [17]. Therefore, it is crucial to control a convenient blood glucose level especially throughout the primal phase of the disease [18]. The most commonly utilized oral hypoglycemics for the disease are sulfonylureas. However these drugs produce severe hypoglycemia and display primary or secondary failure, which is probably associated with their particularities as insulin secretagogues [19]. Therefore, the need for nonsulfonylurea class of hypoglycemic or insulin sensitizers, that does not raise insulin secretion but intensify the action of insulin is urged [20].
  • 8. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 8 of 25 2. PROJECT OBJECTIVES Three main project objectives are stated below: 1- Design, docking and synthesis of novel diabetic medicine. 2- Pharmacological activity evaluation of the medicine. 3- Search for more potent molecules to be used in clinical development for diabetic treatment 3. LITERATURE REVIEW Diabetes mellitus type 2, NIDDM, is a chronic and progressive metabolic disorder of carbohydrate and lipid metabolism and accounts for the remaining 90 % of diabetes mellitus [23]. Type 2 diabetes is a metabolic disorder caused, in part, by insulin resistance in peripheral tissues and/or impaired insulin secretion by the pancreas. In turn, glucose metabolism is decreased in muscle and thus, fat and glucose output by liver rises. The resultant high blood glucose level usually generates many dramatic complications [3]. At the molecular level, the mechanism of insulin resistance in type II diabetes appears to implicate defects in post-receptor signal transduction [24]. The sustained, high plasma glucose levels results in a gradual progression of a number of complications, including neuropathy, nephropathy, retinopathy, and premature athereosclerosis [25]. Therefore, proper glycemic control is, most likely, necessary for the control of diabetic complications in type 2 diabetes during the early stages of the disease [18, 26]. The treatment generally prescribed for type 2 diabetes has been a combination of diet, exercise, and oral hypoglycemic agents such as sulfonylureas and biguanides. Sulfonylureas, which are insulin secretagogues, stimulate insulin secretion from pancreatic -cells and are often recognized to generate severe hypoglycemia [27] and weight gain [28]. In addition, both primary and secondary treatment failure rates with sulfonylureas are high, causing complications [29]. Therefore, drugs that inverse the insulin resistance without activating insulin release from cells achieve a major medical
  • 9. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 9 of 25 need in the therapy of type II diabetes and hence the potentials to decrease long-term complications of NIDDM. However, current therapies to reduce plasma glucose levels have inherent problems including compliance, ineffectiveness, and occurrence of hypoglycemic episodes with insulin and sulphonyl urea.
  • 10. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 10 of 25 1. DESCRIPTION OF THE PROPOSED WORK 4.1 Approach, tasks and phases: Form RE -D1-2:APPROACH UTILIZED FOR ACHIEVING OBJECTIVES OBJECTIVE APPROACH OF ACHIEVING THE OBJECTIVE 1 Design, Docking and Synthesis of novel medicine Here, chemistry will be used to accomplish efficiently the synthesis of intermediates and final products, and the structural identification of compounds through spectroscopic analysis. 2 Pharmacological activity evaluation of the medicine The second objective will be achieved by providing an in-depth pre-clinical assessment of the novel medicine. 3 Search for more potent medicine The structure-activity relationship will be established for the most potent medicine. This study will provide insight into the observed diabetic effects and supply evidence for further development of these compounds for antidiabetic therapy. Form RE -D1-3: MAPPING OF PHASES AND TASKS TO ACHIEVE OBJECTIVES OBJECTIVES PHASES TASKS 1 Design, Docking and Synthesis of novel medicine Phase 1: Preparation for launching the research project Phase 2: Molecular modelling docking study) Phase 3: Synthesis, purification and characterisation of medicine. 1. Setting-up research lab and purchasing chemicals, reagents, solvents, glassware, gas supplies, instruments. 2. Literature review. 1. Construct data base of the 3D structures of medicine. 2. Molecular modelling fitting studies between generate common feature. 1. Investigating, developing, performing and monitoring chemical reactions. 2. Optimization the yield and reaction time using the microwave irradiation instrument. 3. Training students/technicians 4. Evaluation and discussion of the results and writing reports. 2 Pharmacological activity evaluation of the medicine Phase 4: Preparing materials and equipment Acquiring instruments. 1. Tissue culture medicines from insulin action studies and lipid accumulation.
  • 11. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 11 of 25 Phase 5: Assay development and optimisation Phase 6: Biological evaluation 2. RNA extraction 1. Evaluation of compound. 2. Evaluation of compounds for their effects on covalent modification. 3. Evaluation of compounds in cytotoxicity. 4. Evaluation and discussion of the results; final reporting. 3 Search for more potent medicine to be used in clinical development for diabetic treatment Phase 7: Preparation of libraries of medicine for further bio- testing. 1. Acquiring materials. 2. Repeat tasks from objectives 1 and. 3. In vivo evaluation 4. - Writing and submission of a patent - Writing papers in reputable peer reviewed journals. - Participation in conferences to present the findings - Write the progress and final report 4.2 Research methodology Methodology is the systematic, theoretical analysis of the methods applied to a field of study, or the theoretical analysis of the body of methods and principles associated with a branch of knowledge. It, typically, encompasses concepts such as paradigm, theoretical model, phases and quantitative or qualitative techniques.[1] A Methodology does not set out to provide solutions but offers the theoretical underpinning for understanding which method, set of methods or so called “best practices” can be applied to a specific case.
  • 12. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 12 of 25 It has been defined also as follows: 1."the analysis of the principles of methods, rules, and postulates employed by a discipline";[2] 2."the systematic study of methods that are, can be, or have been applied within a discipline";[2] 3."the study or description of methods".[3] In recent years, the word methodology has become a "pretentious substitute for the word method".[4] Many recent uses of the word methodology mistakenly treat it a synonym for method or body of methods. Doing this shifts it away from its true epistemological meaning and reduces it to being the procedure itself, the set of tools or the instruments that should have been its outcome. A methodology is the design process for carrying out research or the development of a procedure and is not in itself an instrument for doing those things. Using it as a synonym for method or set of methods, leads to misinterpretation and undermines the proper analysis that should go into designing research. Generally for any research study both primary and secondary research are done which facilitates in the better understanding of the entire study. Primary research helps garner relevant and adequate data of the current state of affairs pertaining to any subject and provides an insight into the exact nature of the problem. Owing to the broad and complex nature of this research topic which would require delving into many aspects of the study including an ethnographic study which would in turn include a longitudinal time horizon which cannot be possibly encompassed within this research as it goes well beyond the possibilities of an academic research.The use of pre-packaged, 'ready-to-go' methods do not constitute a methodology and are no substitute for the necessary scientific search for the most appropriate method to approach a problem".[ 4.3 Management Plan The Form RE -D1-4: ROLE AND INVOLVEMENT DURATION OF PROJECT TEAM TEAM MEMBERS ROLE DURATION (MONTHS) SENIOR PERSONNEL: Dr. Noman Shah -Supervising and managing the project. -Coordination of the progress work between the two sites -Responsible for administrative, reporting and purchasing requirements. -Conducting all experiments to test the feasibility. -Optimizing yield and reaction time with microwave instrument. -Training staff in synthesis, purification, spectroscopic analysis and microwave instrument. -Following-up the practical work of staff -Interpretation of results -Communicate findings through reports, publications and presentation in international congress. 24 Dr. Hassan Wadood -Designing, docking and performing medicine. -Conducting all experiments to test the feasibility of the approach. 20
  • 13. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 13 of 25 -Optimizing yield and reaction time with microwave instrument. -Training staff in synthesis, purification, spectroscopic analysis and microwave instrument. -Following-up the practical work of staff -Interpretation of results. -Writing reports to PI. -Contribution in writing and submitting paper for publication Dr. Ahmed -Setting up of the cell culture laboratory -Acquiring materials for cell culture, RNA analysis, insulin action and bioassays. --Analysing and reporting of results. -Training students and staff in bio-testing. -Writing of reports, -Contribution in writing and submitting paper for publication. 20 OTHER PERSONNEL: Project Manager - Conducting quotations, purchasing, following up materials -Performing and following up all administrative work -Budgeting - Ticketing 20 Research Assistant M.S. Student Technicians -Conducting chemical reactions, purification -Performing the technical task in the lab, operation instruments and characterization of products -Conducting biological assays -Reporting and evaluating results -Writing first draft report 20 7 14 CONSULTANT: Pr. Bill Gates Providing technical assistance for conducting bio-tests 2 Pr. Stephen Hawking Providing technical assistance for molecular modelling 2
  • 14. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 14 of 25
  • 15. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 15 of 25 FormRE- D1-5: WORK PLAN AND TIME SCHEDUAL 242322212019181716151413121110987654321 INVOLVEMENT DURATION PHASES & TASKS ParticipationPHASE I xxNSTask 1.1: Setting-up research lab and purchasing chemicals, reagents, solvents, glassware, gas supplies, instruments. xxxxxxxNS, HWTask 1.2: Literature review PHASE 2 xxxxxxxNS, HW Task 2.1: Construct data PHASE 3 xxxxxxxxxxxxxxxxxxxNS, HWTask 3.1: Investigating, developing, performing and monitoring chemical reactions. xxxxxxxxxxxxxxxxNS, HWTask 3.2: Optimization the yield and reaction time using the microwave irradiation instrument. xxxxxxxxxxxxxxxxxxxNS, HWTask 3.3: Employing crystallisation, distillation and separation chromatographic techniques. xxxNS, HW, AMTask 3.5: Training students/technicians xxxTask 3.6: Evaluation and discussion of the results and writing reports PHASE 4 Noman Shah (NS), Hassan Wadood (HW), Ahmad (AM)
  • 16. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 16 of 25 4.4 Project Deliverables: FormRE- D1-6: RELATIONSHIP TO STRATEGIC FRAMEWORK2 PROJECT EXPECTED OUTCOMES STRATEGIC TECHNOLOGY PROGRAM GOALS PROJECT OBJECTIVES ACHIEVED GOAL 1 GOAL 2 GOAL3 Development of novel MEDICINE Develop undergraduate and vocation training programs and on-the- job training opportunities to create a pool of technically skilled support staff and technicians who are committed to good laboratories practices Increase national scientific discovery and productivity through dissemination of findings via publications in peer- reviewed and reputed journals 1 Design docking and synthesis of novel medicine Identification of leads as potential potent medicine Develop postgraduate training to create a locally competent talent capable of conducting novel medical and health sciences research Develop mechanism for private fund- raising for research through industry partnerships Establishing national mechanisms for capturing intellectual properties and accelerating their commercialization 2 Pharmacological activity evaluation of the medicine Identify potential drug candidates for diabetic therapy Prepare competitive recruitment package in order to attract, retain and nurture first-class researchers Establish infrastructure to facilitate and expedite acquisition of resources Develop mechanism to encourage research partnerships and create new industries & Promote performance of basic and translational interdisciplinary research for better understanding and treatment of diseases pertinent to the KSA 3 Search for more potent medicine
  • 17. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 17 of 25 The three expected outcomes of this research project allow the achievement of many goals of the Strategic Technology Program Goals (Strategic Priorities for Medical and Health program in Saudi Arabia) described in the form RE-D-1-6. In this section we develop the relationships of the outcomes of the project to the objectives and the linkages with the related goals. OUTCOME 1 (Development of novel medicine)) will be the achievement outcome of the first objective Design, docking and synthesis of novel medicine GOAL 1: Develop undergraduate and vocation training programs and on-the-job training opportunities to create a pool of technically skilled support staff and technicians who are committed to good laboratories practices GOAL 3: Increase national scientific discovery and productivity through dissemination of findings via publications in peer-reviewed and reputed journals OUTCOME 2 (Identification of leads as potential potent medicine) will be the achievement of the second objective: Pharmacological activity evaluation of the medicine systems. GOAL 1: Develop postgraduate training to create a locally competent talent capable of conducting novel medical and health sciences research GOAL 2: Develop mechanism for private fund-raising for research through industry partnerships GOAL 3: Establishing national mechanisms for capturing intellectual properties and accelerating their commercialization OUTCOME 3 (Identify potential drug candidates for diabetic therapy) will be the achievement of the third objective: Search for more potent molecules to be used in clinical development for diabetic treatment. GOAL 1: Prepare competitive recruitment package in order to attract, retain and nurture first-class researchers GOAL 2: Establish infrastructure to facilitate and expedite acquisition of resources GOAL 3: Develop mechanism to encourage research partnerships and create new industries &: Promote performance of basic and translational interdisciplinary research for better understanding and treatment of diseases pertinent to the KSA
  • 18. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 18 of 25 5. VALUE TO THE KINGDOM This research project will be conducted in the field of medicinal chemistry, at the cutting edge of diabetes research. The focus on development of new synthetic drug compounds ended up in amalgamating many other disciplines such as biochemistry, pharmacology, molecular biology and medicine into medicinal chemistry. Umm Al-Qura University, ranked as one of the foremost biotechnology universities in KSA, is committed to providing an exceptional platform in which both researchers and students can excel, and achieve their professional and personal goals. Accordingly, this research project creates foundations for university-based research and its valuable beneficial impact on different levels namely: academia, industry society and economy in KSA. At the academic level, the project will: - provide a multidisciplinary environment that encourages creativity and scientific investment in the field of pharmaceutical technology; working in teams is essential for drug discovery because many different aspects of a molecule (preparation, isolation, characterization, biological and pharmacological studies..) must be identified for a clinical studies candidate. - exploit the research capacity in the Faculty of Pharmacy and the Faculty of Medicine at Umm Al- Qura university for the aim of creating novel knowledge which can be exploited by supporting continuous educational improvement and implementation of new undergraduate and graduate (Master, Ph.D.) curricula. - encourage inter-universities interactions (King Saud University KSA, Newcastle University UK) to generate constructive alliances and synergy between local and/or international researchers and to build affiliations and partnerships with renowned international universities. - offer pharmaceutical industry focused programs as specialized programs to form graduates for career focus tracks in real-world pharmaceutical industry. - train Saudi students to master a wide range of synthetic methods, analytical techniques, medicinal chemistry skills and biological testing methods. Students are placed in a competitive position as they are developed, for a challenging and rewarding professional career in chemical and pharmaceutical research to design, synthesize and identify chemical leads for drug discovery. - facilitate placements of Saudi graduates in pharmaceutical and chemical industry sectors as well as laboratories, research centers, universities and institutes of technology since they may be involved in pharmaceutical research, biological/therapeutic evaluation of medicinal products and production/manufacture, quality control, quality assurance and process development. - offer short courses, workshops, and support seminars for undergraduates and graduates students.
  • 19. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 19 of 25 - generate conferences which can provide a forum for local and international researchers, students, entrepreneurs and industry leaders to deliberate innovation in diabetes therapy. - use the current research center which embodies a highly integrated basic and translational multidisciplinary environment for better understanding and annihilating of diseases pertinent to the KSA. The key to success is converting the latest scientific achievements generated by research into innovative therapeutic treatments able to significantly improve the cure rates for cancer with simultaneous elimination of side effects. The center will extend the spectrum of research interests to cover other areas focused on development of cardiovascular, anticancer and other therapies, with a particular emphasis on understanding the individual's quality of life of the Saudi society. At the industrial, social and economic levels, the interest of developing new local anitdiabetic agents will: - achieve the effective transfer and implementation of research results and technology to medical local institutions in the private and public sectors in KSA and raises their ability to take advantage of the scientific knowledge generated by academia. - bridge the gap between cutting edge academic research and industrial development of diabetes therapeutics and diagnostics. - maximize diabetic patient cost-benefit from publicly funded research in an attempt to tackle concerns about care costs. - ensure the foundations of a modern economy and a modern society in KSA which rely on advanced technology. - deliver better health incomes to diabetic patients by ameliorating their quality and length of life. - improve the access to higher clinical therapeutic quality for Saudi diabetic patients concomitant with the decrease of the costs and deficits of the national health insurance of KSA in the care of patients with chronic diseases. Consequently, this project could pave the way for advancements and betterments in many strategic sectors of the Kingdom.
  • 20. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 20 of 25 6. PROJECT EXECUTION In preamble, we found it necessary to introduce the main researchers of the multi-disciplinary group and the consultancy team who will be involved in the proper execution of this research project. 6.1 Current Resources: This research proposal has not been submitted to any other sources of funding. The physical location of the research at the Faculty of Pharmacy is in dedicated areas for drug discovery and development specifically designated for that purpose. The research center, approx. 80 square meters, is located in the basement of the building of the faculty. It is a modern facility providing all infrastructures essential for general lab operation, including vacuum, compressed gas. The space accommodates 4 fume hoods and 10 benches. The equipments available at Umm Al-Qura University in the Faculty of Pharmacy that will be helpful for the realization of the project are: 1- Infra-Red Spectroscopy (Nicolet 200 from Thermo Company) which will be used for examining the functional group present or absent in the compound. 2- Discovery Studio 3.1 software which will be used to perform molecular modeling of compounds The equipment’s available at Umm Al-Qura University in the Faculty of Medicine that will be helpful for the realization of the project are: 1- Safety cabinet and CO2 incubator will be used for tissue culture of tumor cell lines. 2- UV-Visible spectroscopy from Thermo which will be used for studying the DNA binding and for determining the growth inhibition concentration of molecules using MTT assay. The science library at the Umm Al-Qura University provides an extensive range of chemistry and biology reference texts and major journals. The library also subscribes to a data base in chemistry (Sci-Finder) and to the online journals database Science Direct and ACS which provide access to a worldwide range of scientific research publications. 6.2 Requested Resources: 1] Human resources:
  • 21. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 21 of 25 The proposed project will be conducted in two sites of Umm Al-Qura University (Mecca): College of Pharmacy and College of Medicine. The research team involved in this project will consist of researchers with different fields of expertise: two medicinal chemists and a biochemist (see in preamble of this section). Two research assistants (part-time), one MS student and two technicians will be hired for the project. Many undergraduate students enrolled in pharmacy and chemistry curriculum will have the opportunity to be engaged in this research project at the chemistry-biology interface. They will perform the experiments, measurements, biological tests, and result analyses. A project manager will be recruited to facilitate the administrative work for the realization of the project. 2] Equipments, materials and consumables: Taking into account the nature and complexity of the research proposal, the following resources are necessary for the proper execution of the project: Year 1 Year 2 Supplies: Chemicals, Reagents for synthetic chemistry 60000 30000 Solvents, Chromatography supplies, NMR consumables and amalysis 60000 60000 Elemental analysis for C, H and N 40000 40000 consumables 20000 20000 Service and maintenance of NMR, GC/MS 20000 30000 Tissue culture supplies 100000 20000 Chemicals, reagents, supplies for cell-free experiments 50000 30000 Mice 80000 consumables 30000 30000 Supplies Total: 460000 260000 Instrument CEM Discover focused microwave synthesis instrument 210000 water bath, rotavapor 65000 Total Direct Costs: 735000 260000 SEE INSTRUCTIONS BEFORE COMPLETING FORM RE- D1-7: PROPOSED BUDGET (in Saudi Riyals) PROJECT TITLE: COMPUTRER BASED MOLECULAR MODELING, DRUG DESIGN, SYNTHESIS AND ANTIDIABETIC EVALUATION OF CERTAIN NEW THIAZOLIDINEDIONE (TZD) ANALOGUES FOR DEVELOPING NEW POTENTIAL ANTIDIABETIC TYPE 2 AGENTS DURATION: (24) MONTHS ITEM: CATEGORY NO. COMPENSATION FIRST YEAR SECOND YEAR TOTAL Months Budget Months Budget Manpower Consultants 2 10000 2 40000 2 40000 80000 Principal investigator 1 6000 12 72000 12 72000 144000 Co-investigator 2 5000 10 100000 10 100000 200000
  • 22. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 22 of 25 Co-investigator Research assistants (MS holder) 2 5000 10 100000 10 100000 200000 PhD students Ms students 1 6000 7 42000 42000 Undergrads students Project manager 1 3000 10 30000 10 30000 60000 Technicians 2 2000 7 28000 7 28000 56000 Secretarial- clerical Other Summer compens. Compensation 1 Compensation 2 Total (including summer compensation) 370000 412000 782000 Equipment & materials major equipment ( <= 100.000) 210000 210000 Equipment (> 100,000) 65000 65000 Materials & supplies 460000 260000 720000 Item total 735000 260000 995000 Travel Conferences 10000 10000 Training Field trips Tickets 15000 15000 30000 Item total 15000 25000 40000 Others Patent registration 15000 15000 Publications 10000 10000 Workshop Other expenses 8000 10000 18000 Item total 8000 35000 43000 7% for SCIENCE AND TECHNOLOGY UNIT 84903 55097 140000 Grand total 1212903 787097 2000000 Compensations (including summer compensation) 39.1% 782000 Equipment& materials 49.75% 995000 Travel 2.0% 40000 Others 2.15% 43000 SCIENCE AND TECHNOLOGY UNIT 7 % 140000 Grand total 100% 2000000 6.4 Budget Justification: The proposal entitled “COMPUTRER BASED MOLECULAR MODELING, DRUG DESIGN, SYNTHESIS AND ANTIDIABETIC EVALUATION OF MEDICINE” promises for the Kingdom of Saudi Arabia to achieve all the objectives mentioned in section 2. Consultant: Bill Gates will be approached regarding the biological activity of medicine.
  • 23. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 23 of 25 Their respectively field of expertise will be highly valued for the execution of the project. The participation of research assistants (MS holder, part-time), graduate (MS student), technicians as well as undergraduate students is essential for the execution of the project. They will acquire a variety of techniques and skills from the synthesis to the biological testing. The research team will dedicate maximum time to achieve the goals of this proposal The remuneration of man power is set at 39.1% of the total proposed budget. 49.75% of the total budget is devoted to cover expenses in equipment and material for the proper execution of the project. 2% of the funds will be utilized to enhance knowledge in terms of attending conferences and symposiums in order to execute the project in successfully. 2.15% will be used for patent registration, publications and preparation of the project reports. Finally, 7% of the budget will cover the administrative work of the Science and Technology Unit. Budget justification for acquiring the following instrument: CEM Discovery microwave irradiation instrument will be purchased using the requested funds. The acquisition of this instrument will be beneficial for research activities. It has found many applications in chemical synthesis particularly in the pharmaceutical industry for developing compounds in the lead optimization phase of drug development. The acquisition of such an instrument will enhance the research potential of faculty members, and provide the solid and necessary support for the medicinal chemistry curriculum. The involvement in research activities is necessary for providing training projects to undergraduate and graduate students in the faculty of pharmacy of Umm Al-Qura University in the field of medicinal chemistry.
  • 24. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 24 of 25 8. UNDERTAKING OF THE PROJECT TEAM Form RE- D1-8: UNDERTAKING OF THE PROJECT TEAM The project team undertakes that this project or any part of it, is: 1- Prepared in full conformity with the SCIENTIFIC INTEGRITY RULES. 2- Original work of the signatories or individuals working under their supervision, including the text, graphics, publications, and documents, unless otherwise indicated. 3- Not funded by any other sources. 4- Not submitted to any other funding institution during the evaluation process. 5- Not sought fund from any other sources if it is funded by the NSTIP. SIGNATUREID NUMBER3 NAMEROLE 2321234567 Dr. Noman ShahPI 2321234568 Dr. Hassan Wadood COI. 1 2321234569 Dr. Ahmad COI. 2 3 ID number includes National ID for citizens and Iqama for non-citizens team members.
  • 25. KINGDOM OF SAUDI ARABIA National Science, Technology and Innovation Plan Page 25 of 25 9. REFERENCES: ^ Irny, S.I. and Rose, A.A. (2005) “Designing a Strategic Information Systems Planning Methodology for Malaysian Institutes of Higher Learning (isp- ipta), Issues in Information System, Volume VI, No. 1, 2005. 2.^ Jump up to: a b Methodology Usage Notes, entry at Merriam–Webster 3.Jump up ^ Baskerville, R. (2009). 35. "Computer and Information Security Handbook aha". Computers & Security. Morgan Kaufmann Publications (ᾘ ed.) (Elsevier Inc) 10 (8): 605 Extra |pages= or |at= (help). ISBN 978-0-12-374354-1 4.^ Jump up to: a b misuse of the word Methodology in technical contexts 5.Jump up ^ See, for example, Thomas Kuhn, The Structure of Scientific Revolutions (University of Chicago, 1970, 2nd ed.) 10. RESUMES: