This document describes the synthesis and anticonvulsant evaluation of a series of 2-mercaptobenzimidazole derivatives. A total of 10 derivatives (1A-1J) were synthesized using a Mannich reaction between 2-mercaptobenzimidazole and compounds containing a secondary amine. The structures of the synthesized compounds were characterized using analytical techniques such as melting point, TLC, IR, 1H NMR, and elemental analysis. The anticonvulsant activity of the derivatives was evaluated using a maximal electrical shock induced convulsion method in mice. Most of the synthesized compounds showed significant anticonvulsant activity compared to the control group.
Dear Friends,
This is my 3rd presentation, which will help you to understand the depth knowledge of acute eye irritation/corrosion (OECD-405) study in rabbit.
Expt. 1 Introduction to in vitro pharmacology and physiological salt solutionsVISHALJADHAV100
Definitions of pharmacology & drug
Aims of experimental pharmacology
Pre-clinical pharmacology
Clinical pharmacology
Types of experiments in pharmacology
Assembly for isolated organ/ tissue related experiments
Recording (writing) levers
Physiological salt solution (PSS)
Introduction
Examples
Composition
Role of ingredients
Precautions in preparation of PSS
Selection of PSS
Dear Friends,
This is my 3rd presentation, which will help you to understand the depth knowledge of acute eye irritation/corrosion (OECD-405) study in rabbit.
Expt. 1 Introduction to in vitro pharmacology and physiological salt solutionsVISHALJADHAV100
Definitions of pharmacology & drug
Aims of experimental pharmacology
Pre-clinical pharmacology
Clinical pharmacology
Types of experiments in pharmacology
Assembly for isolated organ/ tissue related experiments
Recording (writing) levers
Physiological salt solution (PSS)
Introduction
Examples
Composition
Role of ingredients
Precautions in preparation of PSS
Selection of PSS
Dr. Jibachha Sah,M.V.Sc( Veterinary pharmacology, TU,Nepal),posted lecturer notes on AUTONOMIC AND SYSTEMIC PHARMACOLOGY for B.V.Sc & A.H. 6 th semester veterinary students of College of veterinary science,Nepal Polytechnique Institute, Bharatpur, Bhojard, Chitwan, Nepal.I hope this lecture notes may be beneficial for other Nepalese veterinary students. Please send your comment and suggestion .Email:jibachhashah@gmail.com,moble,00977-9845024121
Expt. 8 Effect of physostigmine on DRC of acetylcholine using frog rectus abd...VISHALJADHAV100
Objective
Principle
Requirements
Experimental specifications (conditions)
Preparation of ACh and Physostigmine stock and std. solutions
Preparation of frog ringer solution (PSS)
Procedure
Kymograph recording of contractions
Observation table
Calculation of magnification value (Mf)
Graphical presentation of CRC/ DRC
Result and interpretation
This presentation will help understanding the vast process of rat and mice handling and oral routes of drug administration through acute class method (OECD: 423).
Dr. Jibachha Sah,M.V.Sc( Veterinary pharmacology, TU,Nepal),posted lecturer notes on AUTONOMIC AND SYSTEMIC PHARMACOLOGY for B.V.Sc & A.H. 6 th semester veterinary students of College of veterinary science,Nepal Polytechnique Institute, Bharatpur, Bhojard, Chitwan, Nepal.I hope this lecture notes may be beneficial for other Nepalese veterinary students. Please send your comment and suggestion .Email:jibachhashah@gmail.com,moble,00977-9845024121
Expt. 8 Effect of physostigmine on DRC of acetylcholine using frog rectus abd...VISHALJADHAV100
Objective
Principle
Requirements
Experimental specifications (conditions)
Preparation of ACh and Physostigmine stock and std. solutions
Preparation of frog ringer solution (PSS)
Procedure
Kymograph recording of contractions
Observation table
Calculation of magnification value (Mf)
Graphical presentation of CRC/ DRC
Result and interpretation
This presentation will help understanding the vast process of rat and mice handling and oral routes of drug administration through acute class method (OECD: 423).
Synthesis, characterization, in vitro cytotoxic and antioxidant activities of...ijperSS
ABSTRACT
A series of novel (Z)-3-(2-(4-(2-oxo-2H-chromen-3-yl) thiazol-2-yl-)hydrazono)indolin-2-one (8a-8d, 9) were synthesized with various substituted indole derivatives. Structures of the newly synthesized compounds were elucidated by FT-IR, 1H-NMR, 13C-NMR and API-ES Mass spectral data. The in vitro cytotoxic activities of the complexes measurement against the human cancer T-lymphocyte cell lines. In vitro evaluation of these title complexes revealed cytotoxicity from 6.8-18µg/mL against CEM, 9.2-21µg/mL against L1210, 10-19µg/mL against Molt4/C8, 8-12µg/mL against HL60 and 8-16µg/mL against BEL7402. Coumarin derivatives 8c and 8d showed that quite significant anticancer activities. The antioxidant activity of the synthesized compounds was evaluated by DPPH scavenging method. Compounds 8c, 8d and 9 showed significant antioxidant activity compared with that of standard drug, ascorbic acid.
Key words: Coumarin, DPPH, Cytotoxic activity.
An Efficient Synthetic Approach Towards 4-Cyano-3-(Methylthio)-5-Oxo-2H-Pyraz...inventionjournals
ABSTRACT: Synthesis of novel heterocyclic 4-cyano -3-(methylthio)-5-oxo-2H-pyrazole-1(5H)- carbothioamide (3) was prepared by condensing ethyl-2-cyano-3,3-bis (methylthio)acrylate (1) with thiosemicarbazide (2) in DMF and catalytic amount of potassium carbonate. Compound (3) has methylthio group at third position, which is replaced by different nucleophiles such as substituted anilines| phenols| hetryl amines| compounds containing active methylene group to afford 3-substituted derivatives of compound (3). All the newly synthesized compounds were screened for their antimicrobial activity.
Synthesis, Characterization and Biological Evaluation of Substitutedthiazolid...paperpublications3
Abstract: A new series of substituted thiazolidin-4-ones were synthesized and evaluated for anticancer activity by means of MTT assay method for improved anticancer activity .The structures of these synthesized compounds were established by means of IR,H NMR analysis.All the compounds were evaluated for their anticancer activity .Compounds TH10 & TH19 were found most active due to presence of electron withdrawing groups at appropriate position.
N-alkylation methods, Characterization and Evaluation of antibacterial activi...IJERA Editor
A series of new 5-Chloroisatin derivates have been synthesized by the method of N-alkylation at room temperature, in the presence of a base and a catalyst with good yields. The chemical structures of these compounds were confirmed by NMR (1H &13C), these new compounds obtained were evaluated for their antibacterial activity. The final results revealed that the majority of the compounds exhibited good antimicrobial activity against various organisms
Synthesis, Characterization, and Antibacterial Activity of Some Novel 5-Chlor...IJERA Editor
The development of potential antibacterial requires the synthesis of a new series of 5- Chloroisatin derivatives incorporating various aromatic aldehydes in the case 1,3-Dipolar Cycloaddition including Nitrile oxide, as well as the cycloaddition Alcyne-Azide Catalytic with Copper. The charcterization of the structure of the synthesized compounds was confirmed by means of their IR, 1H-NMR and 13C-NMR spectral data. In addition, the antibacterial properties in vitro were tested against certain microorganisms using the disk diffusion technique. A majority of compounds show better activity against several of the microorganisms.
Simple Synthesis of Some Novel Polyfunctionally Derivatives of 2H-Coumarin-2-...IOSRJAC
Compound (2) was prepared from the reaction of ethyl-2-oxo-2H-coumarin-3-carboxylate (1) with ethylcyanoacetate in ethanol containing a catalytic amount of piperidine as catalyst. Compound (2) is the key intermediate for the synthesis of several series of new compounds such as ((pyrimidine, tetrazine, piperidine, oxazepine)-2H-coumarin-2-one derivatives by reaction with selected reagents such as urea, cyanoacetamide, cyanoacetohydrazide, orthoaminophenol and 5-aminotriazole.
Synthesis of substituted 1, 2, 4-triazole derivatives by Microwave irradiationIOSR Journals
Various substituted Triazole-Thiol containing different functional group have been synthesized by microwave method. The title product 1-[(3H-indol-2-ylamino) methyl]-4-phenyl-4, 5-dihydro-1H-1, 2, 4-triazole-3-thiol is synthesized by using amino benzothiazole. The final structures have been established on the basis of their chemical analysis and spectral data. All micro-wave synthesized compounds results into good yield as compared to conventional method of which fluoro substituted compound shows maximum yield.
Indo-American Journal of Agricultural and Veterinary Sciences Journals like IAJAVS play an essential role in the dissemination of scientific knowledge and the advancement of research in their respective fields. Researchers often rely on such journals of the journal papers.
An efficient synthesis, characterization and antibacterial activity of novel ...iosrjce
IOSR Journal of Applied Chemistry (IOSR-JAC) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of applied chemistry and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Chemical Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
SYNTHESIS AND CHARACTERIZATION OF SOME TRANSITION METAL COMPLEXES WITH A NEW ...EDITOR IJCRCPS
A new monodentate phosphorus yield Ph3P=CHC(O)C6H4-m-Br (L),was synthesized and characterized with elemental analysis as
well as various spectroscopic techniques. The reactions of the title ylide with mercury(II) halides in equimolar ratios using dry
methanol as solvent have yielded [L.HgX2]2 (X= Cl (1), Br (2), I (3)). The reaction of 1 equiv. this ylide with Cd(NO3)2.4H2O in the
same solvent give a polynuclear complex [Cd (L)(NO3)(μ-NO3)]n (4), followed by treatment with 2 equiv. AgNO3 and AgOTf led to
monomeric chelate complexes 5 and 6, respectively. Characterization of the obtained compounds was also performed by
elemental analysis, IR, 1H, 31P and 13C NMR. All DMSO-solved synthesized compounds were subjected to biological evaluation for
their antibacterial against 6 Gram positive and negative bacteria effects by disc diffusion method. Results showed antibacterial
activity for studied metal complexes and suggested their possible application as antibacterial agents.
Keywords: Phosphorus yields, mercury(II) complexes, silver(I) complexes, cadmium(II) complexes, antibacterial activity.
Synthesis, characterization and biological activities of novel 2-mercaptobenz...ijperSS
ABSTRACT
A new series of Benzoxazol-2-ylthio-N-(4-substituted) acetohydrazide derivatives (IVa-IVk), were obtained by synthesising new Schiff’s bases derived from benzoxolyl-2-mercaptoaceto hydrazide derivatives by treating with various aryl/hetero aryl aldehydes. Their chemical structures have been confirmed by 1H-NMR, 13C-NMR, FT-IR and ESI-MS spectral data. The synthesised derivatives (IVa-IVk) were screened for their in vitro antimicrobial activities by agar diffusion method. Among the synthesized compounds IVb, IVe, and IVk shown strong antibacterial activity and the compounds IVb, IVe and IVf exhibited strong antifungal activity.
Key words: Benzoxazole, aryl/hetero aryl aldehydes, schiff’s bases, antibacterial activity, antifungal activity.
Chemical Design, Synthesis and Bio-efficacy Screening of New Growth Inhibitor...CrimsonPublishersACSR
The present work aimed to find new growth inhibitors agents spodoptera littoralis (Boisd.), several
inhibitors structurally relevant to the insect growth regulator, Fenoxycarb and the naturally transpiring
juvenile hormone of insects were chemically designed, prepared and evaluated as anti-proliferative agents.
Epihalohydrins derivatives have been synthesized and their agricultural bio-efficacy as insecticides
against spodoptera littoralis (Boisd.). Insecticidal bio-efficacy data showed that that some compounds are
very active against spodoptera littoralis (Boisd.)
Synthesis, Characterization and invitro Anti- inflammatory activity of 1, 3, ...SriramNagarajan19
Oxadiazole derivatives have played a vital part in the development of heterocyclic compounds. In this present work, a series of 5-(2-aminophenyl)-1,3,4-oxadiazole-2(3H)-thione derivatives (1-10) have been synthesized by Mannich reaction. The reaction progress of the synthesized compounds was checked by TLC. The structures of the newly synthesized compounds were confirmed by IR and 1H NMR spectral data. The in-vitro anti-inflammatory activity of 1, 3, 4-oxadiazole compounds (1-10) was assessed by HRBC Membrane Stabilization Method. Among the newly synthesized 1,3,4-oxadiazole derivatives, compounds OFP, OAP, OBNP, OPBNP, ORP, OUP, OPClBP, OFD, OAD and OBND possessed highly significant anti-inflammatory activity at a dose of 1000µg/ml when compared with standard, Diclofenac potassium.
Mixed Ligand, Palladium(II) and Platinum(II) Complexes of Tertiary Diphosphin...Karwan Omer
Palladium(II) and platinum(II) complexes containing the mixed ligands tertiary
diphosphinesdppm. dppp and dppf with Thioester ligand S-1H benzo[d] imidazole-2-yl benzothioate
(HSBIBT) have been prepared by the reaction of PdCl2 and PtCl2 with one equiv of tertiary
diphosphines ligands to form [Pd(k2-dppf)Cl2], [Pd(k2-dppp)Cl2] and [Pt(k2-dppmCl)Cl2] complexes
and then add the ligand HSBIBT to these complexes to form mixed ligand complexes. The prepared
complexes have been characterized by single-crystal X-ray diffraction, elemental analysis, magnetic
susceptibility, molar conductance, IR spectral data and UV-Visible. The results suggested that the
ligand HSBIBT bonded to the metal through N atom and square planner geometries were assigned
for the complexes.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
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We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
Electroconvulsiometer article 2
1. Available online at www.pelagiaresearchlibrary.com
Pelagia Research Library
Advances in Applied Science Research, 2010, 1 (2): 132-138
ISSN: 0976-8610
CODEN (USA): AASRFC
132
Pelagia Research Library
2-Mercaptobenzimidazole Derivatives: Synthesis and
Anticonvulsant Activity
K. Anandarajagopal*1
, Ravi N Tiwari2
, K.G.Bothara2
, J.Anbu Jeba Sunilson1
,
C. Dineshkumar1
and P. Promwichit1
1
School of Pharmacy, Masterskill University College of Health Sciences, Jalan Kemacahaya,
Taman Kemacahaya, Cheras 43200, Selangor, Malaysia
2
SVKM's NMIMS University, School of Pharmacy & Technology Management, Shirpur 425405,
Dhule, Maharashtra
______________________________________________________________________________
ABSTRACT
Totally a series of 2-mercaptobenzimidazole derivatives (1A-1J) were synthesized by mannich
reaction from 2-mercaptobenzimidazole by reaction with compounds having secondary amine
and formaldehyde. The purity of the synthesized compounds was checked by melting point and
TLC and their structure was established by various analytical techniques such as IR and 1
HNMR
spectral studies. Anticonvulsant activity was evaluated for newly synthesized 2-
mercaptobenzimidazole derivatives by maximum electrical shock induced convulsion method.
Most of the synthesized compounds exhibited highly significant anticonvulsant activity.
Keywords: 2-mercaptobenzimidazole, Mannich reaction, Anticonvulsant
______________________________________________________________________________
INTRODUCTION
Discovery of new drugs that is therapeutically useful and goes in to clinics is a lifetime dream for
medicinal chemist. Carbocyclic or heterocyclic ring systems comprise the core of chemical
structures of the vast majority of therapeutic agents. The exploitation of a simple molecule with
different functionalities for the synthesis of heterocyclic compounds is a worthwhile contribution
in the chemistry of heterocycles [1]. There is still interest in the synthesis of benzimidazole
derivatives for obtaining new biologically active compounds because of their diverse biological
activity such as anti-HIV [2], anthelmintic [3], antibacterial [4], antifungal [5], CNS depressant
[6], analgesic [7] and anti-inflammatory [8] activities.
2. K. Anandarajagopal et al Adv. Appl. Sci. Res., 2010, 1 (2):132-138
______________________________________________________________________________
133
Pelagia Research Library
2-mercaptobenzimidazole derivatives, one of the most important derivatives of benzimidazole
exhibited a wide variety of interesting biological activities such as antimicrobial [9],
antihistamine [10], neutropic [11] and analgesic [12] activities. In recent years, the field of
anticonvulsant drug development has become quite dynamic, affording many promising research
opportunities. Our earlier reports with 2-mercaptobenzimidazole derivatives have driven to the
present investigation. In continuation to our work on 2-mercaptobenzimidazoles, the present
work focuses on 2-mercaptobenzimidazole derivatives and their anticonvulsant evaluation.
MATERIALS AND METHODS
General
Starting materials and reagents used were procured from commercial suppliers. Melting points
were determined by open-ended capillary tube on Veego electrical melting point apparatus and
were uncorrected. The purity of the compounds were checked by TLC using Silica Gel as
stationary phase and chloroform-methanol (9:1) as eluent and the spots were visually detected in
an Iodine chamber. The structure of the synthesized compounds was elucidated by IR spectra in
υmax (cm-1
) on FT-IR (Shizmadu-8400 series) using KBr disc technique and 1
H NMR spectra in δ
units (ppm) relative to an internal standard of tetramethylsilane on 1
H NMR (Brucker 400 MHz)
in DMSO-d6. Elemental analyses for final compounds were performed on Carlo Erba 108 and
the observed values were within the acceptable limits (±0.4%). The synthetic method is depicted
in Scheme 1.
Procedure for the synthesis of novel 2-mercaptobenzimidazole derivatives (1A-1J)
2-mercaptobenzimidazole was synthesized by the method described by Maw-Ling Wang et al
[13]. Equimolar quantities (0.01 mol) of 2-mercaptobenzimidazole and the respective
compounds having secondary amine were dissolved in methanol (30 mL) in a beaker under
perfect ice-cold condition and stirred constantly. To this solution, formaldehyde (0.01 mol) was
added slowly and heated to reflux for 3 h. The content was kept overnight in the freezer. The
corresponding crystals of mannich base of 2-mercaptobenimidazole obtained was recrystallized
from alcohol [14].
Physical data of newly synthesized 2-mercaptobenzimidazole derivatives
2-(isoindol-1,3-dione-N-methyl)mercapto-1H-benzimidazole (1A)
Yield 69%; m.p. 143-1450
C; Rf 0.4836. IR (KBr, cm-1
): 3366 (NH), 3061 (ArCH), 1751 (C=O),
1601 (C=N), 1463 (CH2), 1351 (C-N). 1
H NMR (DMSO-d6, ppm)δ: 5.29 (s, 1H, NH), 5.78 (s,
2H, CH2), 7.26 - 8.06 (m, 8H, ArH). Anal. Calc. for C16H11N3O2S: C 62.12, H 3.58, N 13.58.
Found: C 62.10, H 3.56, N 13.56%.
2-(diphenylamine-N-methyl)mercapto-1H-benzimidazole (1B)
Yield 72%; m.p. 135-1380
C; Rf 0.6211. IR (KBr, cm-1
): 3354 (NH), 3113 (ArCH), 1605 (C=N),
1461 (CH2), 1354 (C-N). 1
H NMR (DMSO-d6, ppm)δ: 4.72 (s, 2H, CH2), 5.12 (s, 1H, NH), 6.76
– 7.98 (m, 14H, ArH). Anal. Calc. for C20H17N3S: C 72.48, H 5.17, N 12.68. Found: C 72.42, H
5.14, N 12.64%.
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2-(N-phenylacetamide-N-methyl)mercapto-1H-benzimidazole (1C)
Yield 74%; m.p. 164-1660
C; Rf 0.3288. IR (KBr, cm-1
): 3356 (NH), 3021 (ArCH), 1663 (C=O),
1598 (C=N), 1463 (CH2), 1423 (CH3), 1352 (C-N). 1
H NMR (DMSO-d6, ppm)δ: 2.38 (s, 3H,
CH3), 5.14 (s, 2H, CH2), 5.32 (s, 1H, NH), 7.16 – 7.76 (m, 9H, ArH). Anal. Calc. for
C16H15N3OS: C 64.62, H 5.08, N 14.13. Found: C 64.58, H 5.06, N 14.10%.
2-(indol-N-methyl)mercapto-1H-benzimidazole (1D)
Yield 72%; m.p. 113-1150
C; Rf 0.5434. IR (KBr, cm-1
): 3339 (NH), 3063 (ArCH), 1616 (C=N),
1461 (CH2), 1347 (C-N). 1
H NMR (DMSO-d6, ppm)δ: 5.18 (s, 1H, NH), 5.48 (s, 2H, CH2), 6.64
– 7.82 (m, 10H, ArH). Anal. Calc. for C16H13N3S: C 68.79, H 4.69, N 15.04. Found: C 68.74, H
4.66, N 14.98%.
2-(piperazin-N-methyl)mercapto-1H-benzimidazole (1E)
Yield 78%; m.p. 184-1860
C; Rf 0.7128. IR (KBr, cm-1
): 3352 (NH), 2996 (ArCH), 2910 (CH),
1616 (C=N), 1457 (CH2), 1339 (C-N). 1
H NMR (DMSO-d6, ppm)δ: 1.94 (s, 1H, NH), 2.34 (t,
4H, CH2), 2.77 (t, 4H, CH2), 4.31 (s, 2H, CH2), 5.11 (s, 1H, NH), 7.16 – 7.88 (m, 4H, ArH).
Anal. Calc. for C12H16N4S: C 58.04, H 6.49, N 22.56. Found: C 58.00, H 6.44, N 22.52%.
2-(morpholin-N-methyl)mercapto-1H-benzimidazole (1F)
Yield 76%; m.p. 130-1320
C; Rf 0.6624. IR (KBr, cm-1
): 3324 (NH), 3060 (ArCH), 2950 (CH),
1610 (C=N), 1448 (CH2), 1345 (C-N). 1
H NMR (DMSO-d6, ppm)δ: 2.76 (t, 4H, CH2), 3.70 (t,
4H, CH2), 3.90 (s, 2H, CH2), 5.13 (s, 1H, NH), 7.27 – 7.36 (m, 4H, ArH). Anal. Calc. for
C12H15N3OS: C 57.81, H 6.06, N 16.85. Found: C 57.78, H 6.02, N 16.82%.
2-((4-hydroxy-N-phenylacetamide)-N-methyl)mercapto-1H-benzimidazole (1G)
Yield 68%; m.p. 1730
C; Rf 0.4221. IR (KBr, cm-1
): 3453 (OH), 3283 (NH), 3010 (ArCH), 1750
(C=O), 1226 (ArOH), 1359 (C-N), 1447 (CH3), 1459 (CH2) 1613 (C=N). 1
H NMR (DMSO-d6,
ppm)δ: 2.38 (s, 3H, CH3), 5.22 (s, 1H, OH), 5.65 (s, 2H, CH2), 5.08 (s, 1H, NH), 6.78 – 7.42 (m,
8H, ArH). Anal. Calc. for C16H15N3O2S: C 61.32, H 4.82, N 13.41. Found: C 61.28, H 4.78, N
13.42%.
2-(2,4,5-triphenyl-1H-imidazol-N-methyl)mercapto-1H-benzimidazole (1H)
Yield 66%; m.p. 189-1920
C; Rf 0.6711. IR (KBr, cm-1
): 3283 (NH), 3063 (ArCH), 1457 (CH2)
1589 (C=N), 1357 (C-N). 1
H NMR (DMSO-d6, ppm)δ: 5.08 (s, 1H, NH), 5.77 (s, 2H, CH2),
7.12 – 8.28 (m, 19H, ArH). Anal. Calc. for C29H22N4S: C 75.95, H 4.84, N 12.22. Found: C
75.92, H 4.82, N 12.18%.
2-(N-phenylbenzamide-N-methyl)mercapto-1H-benzimidazole (1I)
Yield 78%; m.p. 118-1200
C; Rf 0.6268. IR (KBr, cm-1
): 3285 (NH), 3019 (ArCH), 1751 (C=O),
1460 (CH2), 1359 (C-N), 1599 (C=N). 1
H NMR (DMSO-d6, ppm)δ: 4.86 (s, 2H, CH2), 5.75 (s,
1H, NH), 6.92 - 7.98 (m, 14H, ArH). Anal. Calc. for C21H17N3OS: C 70.17, H 4.77, N 11.69.
Found: C 70.14, H 4.76, N 11.66%.
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2-(indole-2,3-dione-N-methyl)mercapto-1H-benzoimidazole (IJ)
Yield 72%; m.p. 1600
C; Rf 0.3128. IR (KBr, cm-1
): 3349 (NH), 3012 (ArCH), 1729 (C=O), 1462
(CH2), 1615 (C=N), C-N (1333). 1
H NMR (DMSO-d6, ppm)δ: 4.88 (s, 1H, NH), 5.32 (s, 2H,
CH2), 6.94 - 8.26 (m, 8H, ArH). Anal. Calc. for C16H11N3O2S: C 62.12, H 3.58, N 13.58. Found:
C 62.10, H 3.56, N 13.54%.
Anticonvulsant Activity
Animals
Adult albino mice (20-30 g) were used for this study. All the animals were housed in standard
cages, at room temperature (25 ± 3°C), with 12 h dark/12 h light cycles and were fed with
standard pellets and water was provided ad libitum. All animal experiments were conducted
under the standard conditions of the Animal Scientific Procedures. The experimental protocol for
animal study was approved by the institutional animal ethical committee
(AKCP/CPCSEA/509/F(1h)/2007).
Method
The anticonvulsant activity was carried out by maximal electrical shock induced convulsion
method [15]. Mice were treated with control (2% w/v Tween 80), titled compounds (20 mg/mL,
ip) and standard drug, phenytoin (5 mg/mL, ip) [16]. After 30 min, the animals were subjected to
electro shock through ear electrodes of 150 mA for 0.2 sec by electroconvulsiometer. The
duration of time for extensor response was noted. The reduction in the time or abolition of the
hind limb tonic extension component of the seizure was defined as protection in the MES test.
Similarly readings for control and standard were also noted and the readings are subjected to
preliminary statistical analysis and tabulated in Table 1. The anticonvulsant activity was
measured in terms of percentage protection of extensor phase.
Statistical analysis
All the results are expressed as mean ± SEM. The values obtained for the above parameters in
synthesized compounds were compared with control group using One-Way ANOVA followed
by students “t” test [17]. The values of P < 0.01 and P < 0.001 were considered to indicate a
significant difference between the groups.
RESULTS AND DISCUSSION
A series of 10 novel mannich bases of 2-mercaptobenzimidazole derivatives were synthesized
using mannich reaction by the reaction between compounds having secondary amine and
formaldehyde. The formation of new chemical analogues was indicted by the melting point and
Rf value. The structure of the synthesized compounds was established by spectral (IR and 1
H
NMR) as well as elemental analysis data. The NH band (3283 - 3356 cm-1
) and NH proton signal
(4.88 – 5.75 ppm) of 2-mercaptobenzimidazole in IR and 1
H NMR spectrum respectively in all
the synthesized compounds confirmed the reaction was not taken at 1H position. The presence of
CH2 stretching (1448 - 1463 cm-1
) and CH2 proton signal (3.70 – 5.78 ppm) in IR and 1
H NMR
spectrum respectively together with the absence of SH proton of 2-mercaptobenzimidazole
confirmed the formation of the titled compounds.
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Compound
Code N
R R1
1A
O
O
N
1B N
1C H3C
O
N
1D N
1E N
HN
1F N
O
1G
O
N
OH
H3C
1H N
N
Ph
Ph
Ph
1I
O
N
1J
NO
O
N
H
N
SH
CH2O
N
H
N N
2-mercaptobenzimidazole
Formaldehyde
20
amine Reflux 3 h
R1
RS
NH2
NH2
C
S SMethanol
KOH
Ortho phenylene diamine
Carbondisulphide
Methanol
N
H
R R1
1A - 1J
SCHEME-1
Where,
Table 1: Anticonvulsant activity of titled compounds
Compound code
Duration of time of
Extensor Phase (Sec)
Mean ± SEM
% Protection
Control 18.47 ± 0.82 -
Standard 2.43 ± 1.23** 86.84
1A 13.65 ± 1.11* 26.10
1B 4.44 ± 0.89** 75.96
1C 11.36 ± 0.18* 38.49
1D 3.23 ± 1.40** 82.51
1E 2.59 ± 0.32** 85.98
1F 3.65 ± 1.11** 80.24
1G 10.68 ± 0.72** 42.76
1H 4.76 ± 1.04** 74.22
1I 3.32 ± 0.62** 82.02
IJ 5.76 ± 1.04** 68.81
Values are Mean ± SEM, *P < 0.01 and **P < 0.001 statistically significant from control group
(n=6)
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All the synthesized compounds have a tendency to causing a significant reduction in duration of
the stimulated extensor phase. All the synthesized compounds at a dose of 20 mg/kg, ip exhibited
anticonvulsant activity (26.10 – 85.98 % protection) against maximum electrical shock induced
convulsion compared with the standard drug phenytoin (Table 1). Compounds 1E, 1F and 1I
exhibited excellent anticonvulsant activity
CONCLUSION
The present study concluded that the experimental procedures make this methodology a better
modesty for the synthesis of the titled compounds for possible anticonvulsant activity. All the
tested compounds with structural modifications exhibited promising anticonvulsant activity.
From these findings, it can be suggested that the designing of new chemical analogues with 2-
mercaptobenzimidazoles lead the necessity for the development of further research.
Acknowledgements
The authors are thankful to the Management, Arulmigu Kalasalingam College of Pharmacy,
Krishnankoil, Tamilnadu, India for providing facilities and technical assistance. Also the authors
are grateful to Dato’ Sri Edmund Santhara, GCEO, and Dato’ Prof. Dr. Nik Rahimah Binti Nik
Yacob, Vice Chancellor, Masterskill University College of Health Sciences, Malaysia, for their
funding, continuous encouragement and support.
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