3. INTRODCUTION
CELLSARE THE BASIC UNITSTHAT MAKE UPTHE HUMAN
BODY.
CELLSGROWAND DIVIDETO MAKE NEW CELLSASTHE BODY
NEEDSTHEM .
January 21 K.SATTANATHAN M.PHARM 3
5. INTRODCUTION
CANCER IS AN ABNORMAL CELL DIVIDEWITHOUT CONTROL AND
CAN INVADE NEARBYTISSUES.
THESE ABNORMAL CELLS ARETERMED CANCER CELLS,
MALIGLNANT CELLS ORTUMOR CELLS
CANCER CELLS CAN ALSO SPREADTO OTHER PARTS OFTHE BODY
THROUGHTHE BLOOD AND LYMPH SYSTEM.
THIS PROCESS OF CANCER CELLS LEAVING AN AREA ISTERMED
METASTATIC SPREAD OR METASTASIS.
January 21
K.SATTANATHAN M.PHARM
5
8. INTRODCUTION
Most cancers form a lump called a tumor or a growth. But not all
lumps are cancer.
Lumps that are not cancer are called benign
Lumps that are cancer are called malignant
Some cancers, like leukemia (cancer of the blood), don’t form
tumors.They grow in the blood cells or other cells of the body.
January 21 K.SATTANATHAN M.PHARM 8
12. INTRODUCITON
CANCER IS LEADINGCAUSE OF DEATH INWORLDWIDE . IT
ACCOUNTED FOR 9.6 MILLION DEATH
LUNG, PROSTATE , CERVICAL, STOMACH, LIVER,COLON,AND
BREAST CANCER CAUSETHE MOST CANCER DEATH EACH
YEAR
January 21 K.SATTANATHAN M.PHARM 12
14. INTRODUCTION
G1 PHASE OR GAP PHASE INWHICHTHE CELLGROWTH AND
PREPARETO SYNTHESIS DNA
S PHASE OR SYNTHESIS PHASE INWHICHTHE CELL SYNTHESIS
DNA
G2 PHASE OR SECONDGAP, PHASE INWHICHTHE CELL
PREPARETO DIVIDEAND
M PHASE OR MITOSIS PHASE INWHICH CELL DIVISIONOCCURS
G0 PHASE IS A NON PROLIFERATIVE PHASE
January 21 K.SATTANATHAN M.PHARM 14
15. INTRODUCTION
TYPES OF CANCER
CARCINOMA
SARCOMA
LEUKEMIA
LYMPHOMA
MYELOMA
MELANOMA
NEUROENDOCRINE TUMOURS
CARCINOID TUMOURS
January 21 K.SATTANATHAN M.PHARM 15
16. INTRODUCTION
CARCINOMA
It is the most common form of cancer that affects the epithelial
cells which form the lining of internal organs or the skin
SARCOMA
These cancer cells develop in the bones and soft tissues such
as fat tissues, cartilages, blood vessels, lymph and other
supporting tissues of tendons and ligaments.
The most common form of sarcoma in the bone is
osteosarcoma, and in soft tissues include Kaposi sarcoma,
liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma,
and dermatofibrosarcoma protuberans.
LEUKAEMIA
Commonly known as blood cancer, leukaemia affects the tissues of
the bone marrow which is responsible for blood production. It is one
of the fatal forms of cancer.
January 21 K.SATTANATHAN M.PHARM 16
17. INTRODUCTION
CAUSES OF CANCER
CANCER CAN BE CAUSED BY MANY
THINGS INCLUDING EXPOSURE TO
CANCER- CAUSING SUBSTANCE,
CERTAIN BEHAVIORS, AGE, AND
INHERITED GENETIC MUTATIONS
January 21 K.SATTANATHAN M.PHARM 17
18. INTRODUCTION
PHYSICAL CARCINOGEN SUCH AS ULTRAVIOLET AND IONIZING
RADIATION
CHEMICAL CARCINOGEN SUCH AS ASBESTOS, TOBACCO,
AFLATOXIN,AND ARSENIC
BIOLOGICAL CARCINOGENS SUCH AS INFECTIONS FROM
CERTAINVIRUSES, BACTERIA OR PARASITES.
January 21 K.SATTANATHAN M.PHARM 18
20. INTRODUCTION
UNUSUAL BLEEDING
PERSISTANT COUGH
CHANGES IN BOWEL OR BLADDER HABITS
PERSISTENT LUMP
A SORETHAT DOES NOT HEAL
INDIGESTION OR SWALLOWING TROUBLE
CHANGE IN APPEARANCE OF MOLE OR
WART
January 21 K.SATTANATHAN M.PHARM 20
24. INTRODUCTION
THE GREEK PHYSICIAN HIPPOCRATES USED IN NAME
CARCINOMA FROM THE GREEK WORK KARCINOS. IT MEANING
CRAB . IT REFERS TO THE SHELL- LIKE SURFACE, LEGLIKE
FILAMENTS, AND SHARP PAIN OFTEN ASSOCIATED WITH
TUMORS
IN 1968 RESEARCHER DEMONSTRATED THAT WHEN A
TRANSFORMING VIRUS INFECTS A NORMLA CELL, IT INSERTS
OND OF ITS GENES INTOTHE HOST CELLGENOME
AN ONCOGENE,”SRC” WAS THE FIRST DISCOVERED CANCER
GENE
January 21 K.SATTANATHAN M.PHARM 24
29. INTRODUCTION
CANCER CHEMOTHERAPY IS THE TREATMENT OF CANCER
USINGANTICANCER DRUGS.
THESE DRUGS ARE OFTEN USED AS PART OF MULTIMODALITY
THERAPY, THAT IS, ALONG WITH SURGERY AND/OR
RADIOTHERAPY,TOACHIEVE AND MAINTAIN REMISSION
January 21 K.SATTANATHAN M.PHARM 29
42. STRUCTURE
OFANTI
CANCER
AGENTS
BUSULFAN
IUPAC NAME: : 1, 4-
Butanediol
dimethanesulphonate
MELTING POINT: 106 -107
in Celsius
SOLUBILITY: soluble in
acetone
LOG P : -0.52
January 21 K.SATTANATHAN M.PHARM 42
43. STRUCTURE
OFANTI
CANCER
AGENTS
VINCRISTINE
It is alkaloid obtained from
the plant of vica rosesus
Family : apocyanaceae
MELTING POINT: 218
SOLUBILITY: soluble in water
pKa: 5.4
January 21 K.SATTANATHAN M.PHARM 43
44. STRUCTURE
OFANTI
CANCER
AGENTS
VINBLASTINE
It is alkaloid obtained from
the plant of vica rosesus
Family : Apocyanaceae
Melting point: 267 in Celsius
Solubility : soluble in alchols
Log p: 3.7
pKa: 5.4, 7.4
January 21 K.SATTANATHAN M.PHARM 44
45. STRUCTURE
OFANTI
CANCER
AGENTS
ETOPOSIDE
BINOMICAL NAME:
PODOPHYLLUM PELTATUM
RESULTING IN DNA
DAMAGETHROUGH
STRAND BREAKAGE
INDUCED BYTHE
FORMATION OFTERNARY
COMPLEXOF DRUG, DNA
AND ENZYME
January 21 K.SATTANATHAN M.PHARM 45
46. STRUCTURE
OFANTI
CANCER
AGENTS
FLURO URACIL
IUPAC NAME: 5-Fluoro-2, 4
(1H, 3H)-pyrimidinedione
Melting point: 283 in Celsius
Solubility : soluble in water
and methanol
Log p : -0.89
pKa: 8. 02
January 21 K.SATTANATHAN M.PHARM 46
48. STRUCTURE
OFANTI
CANCER
AGENTS
AZATHIOPRINE
IUPAC NAME : 6-[1-Methyl-4-
nitromidazole-5 yl] thio] purine
Melting point: 243.5 in Celsius
Solubility ; Insoluble in water ,
very slightly soluble in ethanol
Log p ; 0.1
PKA 7.8
January 21 K.SATTANATHAN M.PHARM 48
49. STRUCTURE
OFANTI
CANCER
AGENTS
THIOGUANINE
IUPAC NAME 2-amino-3,7-
dihydropurine-6-thione
MELTING POINT:
GREATER THAN 360 IN
CELSISUS
SOLUBILITY: INSOLUBLE
IN WATER , FREELY
SOLUBLE IN ALKALI
SOLUTION
LOG p: -0.07
January 21 K.SATTANATHAN M.PHARM 49
50. STRUCTURE
OFANTI
CANCER
AGENTS
METHOTREXATE
IUPAC NAME : (2S)-2-[[4-
[(2,4-diaminopteridin-6-
yl)methyl-
methylamino]benzoyl]amino]
pentanedioic acid
MELTING POINT :195 IN
CELSIUS
SOLUBILITY : INSOLUBLE
IN WATER
LOG P: -1.85
PKA: 4.7
January 21 K.SATTANATHAN M.PHARM 50
55. STRUCTURE
OFANTI
CANCER
AGENTS –
bleomycin
Bleomycin sulfate is a mixture of cyto toxic water soluble basic
glycopeptide antibiotics isolated by fermentation broth of
Streptomyces verticillus
bleomycin is used as a Squamous cell carcinoma, Hodgkin’s
disease,Testicular and Overian carcinoma, and malignant plueral
effusion.
January 21 K.SATTANATHAN M.PHARM 55
57. STRUCTURE
OFANTI
CANCER
AGENTS –
MITOMYCIN
MITOMYCIN IS A DISCOVERED IN A METABOLITE OF
STREPTOMYCESCAESPITOSUS
MITOMYCINS APPAR- ENTLY WERE THE FIRST OF THE USEFUL
BIOREDUCTIVELY ACTIVATED DNA ALKYLATING AGENTS TO BE
DISCOVERED.
TREATMENT OF DISSEMINATED ADENOCARCI- NOMA OF THE
STOMACH, COLON,OR PANCREAS
MEDICINAL CHEMISTRY ASPECTS THAT THE PARTICIPATIONOF
THE C-7 SUBSTITUENT IN ACTIVATION BY THIOLS DIFFERS
SIGNIFICANTLY WHEN C-7 BEARS A METHOXYL GROUP (THE
MITOMYCIN A SERIES) COMPARED TO THE ACTIVATION WHEN
C-7 BEARS AN AMINOGROUP (THE MITOMYCINC SERIES)
January 21 K.SATTANATHAN M.PHARM 57
58. STRUCTURE
OFANTI
CANCER
AGENTS –
MITOMYCIN
MitomycinC undergoes enzymatic reductive activation to produce
reactive species capable of bis alkylation and crosslinking of DNA,
resulting in inhibition of DNA bio synthesis
January 21 K.SATTANATHAN M.PHARM 58
64. MECHANISM
OFANTI
TUMOUR
AGENTS
THE GENERAL MODE OF ACTION OF ALKYLATING
AGENTS CENTRES AROUND THE FORMATION OF AN
ETHYLENEIMONIUM ION INTERMEDIATE, WHICH IS
HIGHLY UNSTABLE AND FORMS COVALENT BONDS
WITH DNA BASES, THE MOST VULNERABLE TO
ATTACK BEING GUANINE.
January 21 K.SATTANATHAN M.PHARM 64
65. MECHANISM
OFANTI
TUMOUR
AGENTS
THESE DRUGS TYPICALLY POSSESS TWO REACTIVE GROUPS
CHARACTERIZED BY THE PRESENCE OF A LONE PAIR OF
ELECTRONS ON THE NITROGEN ATOM, DONATION OF WHICH
GIVING RISE TO AN UNSTABLE ETHYLENEIMONIUM ION
FOLLOWING LOSS OF A NEGATIVELY CHARGED CHLORIDE
RADICAL.
January 21 K.SATTANATHAN M.PHARM 65
66. MECHANISM
OFANTI
TUMOUR
AGENTS
January 21 K.SATTANATHAN M.PHARM 66
THE MAJOR SITE OF ALKYLATION WITHIN DNA IS THE N 7
POSITION OF GUANINE, HOWEVER OTHER BASES ARE ALSO
ALKYLATED TO LESSER DEGRESS, INCLUDING N1 AND N3 OF
ADENINE, N3 OF CYTOSINEAND O6 OF GUANINE
69. MECHANISM
OFANTI
TUMOUR
ANTI
METABOLITE
ANTI METABOLITE ANTI CANCER AGENTS HAVE A SIMILAR
MOLECULAR STRUCTURE TOSUBSTRATE OF ENZYMES
INVOLVED IN THE SYNTHESIS OF DNA , A PROCESS THAT
EVENTUALLY DISRUPTS DNA STRUCTURE AND
FUNCTIONALITYAND LEADSTOTUMORCELL DEATH.
THESE DRUGS MAY INTERACTWITHTWO WAYS
1. STRUCTURALANALOGSOF PRECURSOR
2. INTERMEDIATEALONGTHE SYNTHETICCHAIN
January 21 K.SATTANATHAN M.PHARM 69
70. MECHANISM
OFANTI
TUMOUR
ANTI
METABOLITE
FOLIC ACID IS IMPORTANT DNA PRECURSOR WHICH
UNDERGOES REDUCTION TO DIHYDRO FOLATE AND
FURTHER REDUCED TO TETRA HYDRO FOLATE IN
THE PRESENCE OF DIHYDRO FOLATE REDUCATSE
(DHFR) AND NADPH .
AN ANTI TUMOR AGENT METHOTREXATE MAINLY
TARGETED TO AN ENZYME OF DIHYDRO FOLATE
REDUCTASE
January 21 K.SATTANATHAN M.PHARM 70
71. MECHANISM
OFANTI
TUMOUR
ANTI
METABOLITE
REDUCED FOLATE ACT AS A CO FACTOR FOR THYMIDYLATE
SYNTHASE , WHICH CATALYSE THE SYNTHESIS OF PYRIMDINE
NUCLEOTIDES BY CONVERTING DEOXYURIDINE MONO
PHOSPHATETO DEOXYTHYMIDINE PHOSPHATE
FOLATE ANALOGUES INHIBIT THE SYNTHESIS OF BOTH
PURINES AND PYRIMIDINES ALTHOUGH DRUGS WITH IN THIS
CLASS DIFFER IN THEIR RELATIVES SPECIFITIES AS INHIBITOR
OF DHFR ANDTHYMIDINE SYNTHASE FUNCTION
January 21 K.SATTANATHAN M.PHARM 71
73. MECHANISM
OFANTI
TUMOUR
ANTI
METABOLITE
DACTINOMMYCIN BINDS NON COVALENTLY TO DOUBLE STRANDED DNA
BY PARTIAL INTERCALATION BETWEEN ADJACENT GUANINE CYSTOSINE
BASES RESULTING IN INHIBITONOF DNA FUNCTION
THE STRUCTURE FEATURE OF DACTINOMYCIN IMPORTANT FOR ITS
MECHANISM OF CYTOTOXICITY IS THE PLANAER PHENOXAZONE RING,
WHICH FACILITATES INTERACTION BETWEEN DNA BASE PAIRS.
THE PEPTIDE LOOPS ARE LOCATED WITHIN THE MINOR GROOVE AND
PROVIDE FORADDITIONAL INTERACTION
THE PREFERENCE FOR GPC BASE PAIRS IS THOUGHT TO BE PARTLY
RELATED TO THE FORMATION OF HYDROGEN BOND BETWEEN THE 2
AMINO GROUPS OF GUANIINE AND THE CARBONYL OF THE L-THREONINE
RESIDUES.
January 21 K.SATTANATHAN M.PHARM 73
