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NATURAL PRODUCT LIBRARY'S ROLE IN DRUG DISCOVERY

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NATURAL PRODUCT DERIVED COMBINATORIAL LIBRARY AND IT’S SIGNIFICANCE IN DRUG DISCOVERY PROGRAMMES Presented by: ANZAR ALAM M.Pharm 2 nd Sem Pharmacognosy & Phytochemistry FACULTY OF PHARMACY JAMIA HAMDARD Presented to: Dr. (Prof.) S.H.Ansari Dean Student Welfare (DSW) JAMIA HAMDARD
Prelude ,[object Object],[object Object],[object Object]
Drug Discovery 1 ,[object Object],[object Object],[object Object]
The Long Road to a New Medicine Discovery Exploratory Development Full Development Registration Large Amounts of Candidate Medicine Synthesized Project Team and Plans Synthesis of Compounds Early Safety Studies Candidate Formulations Developed Extensive Safety Studies Screening Studies in Healthy Volunteers Phase I Candidate Medicine Tested in 3-10,000 Patients (Phase III) Studies in 100-300 Patients (Phase II) Clinical Data Analysis
Disease Selection 1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Drug Target Selection 1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Identification of Bioassay Method 1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Search for Lead Compound 1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Lead Compound from Natural Source 1, ,[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],vanomycin
Combinatorial Library
WhyCombinatorial Library ? 1 ,[object Object],[object Object],[object Object],[object Object],Gly (G) Val (V) Ala (A) G GGG GVG GAG G GGV GVV GAV V GGA GVA GAA A V VGG VVG VAG G VGV VVV VAV V VGA VVA VAA A A AGG AVG AAG G AGV AVV AAV V AGA AVA AAA A
Combonatorial Methods 1,3 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Combinatorial Method & Requirements 1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Solid Support 1,3 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Linkers
Bond formation & bond breaing 1 ,[object Object],[object Object],[object Object]
Bond formation & bond breaing (cont….) ,[object Object],[object Object]
Mixed combinatorial synthesis 1 ,3 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Mixed combinatorial synthesis (cont…) ,[object Object],[object Object],[object Object],[object Object]
Par allel synthesis 3
Other Methods 1,3 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Synthesis of Benzodiazipine Library 3
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Advantages & Role of Combinatorial synthesis 1 ,3
NATURAL PRODUCT DERIVED COMBINATORIAL LIBRARY Biological Screening Startig Materials Combinatorial Synthesis Desired Activity No Desired Activity Possible Drug Candidate Combinatorial Library ( for future Drug Candidate)
[object Object],[object Object],[object Object],[object Object],Epothilones
[object Object],[object Object],[object Object],[object Object],Epothilones (cont..)
Sugar-derived oxacycles 9, ,[object Object],[object Object],[object Object],[object Object]
Vitamin D 12 ,[object Object],[object Object],[object Object]
Library Production of Vitamin.D 13 ,[object Object],[object Object],[object Object]
Fumitremorgin C 14 ,[object Object],[object Object],[object Object],[object Object],[object Object]
Hapalosin 15,16 ,[object Object],[object Object],[object Object],[object Object],[object Object]
Psammaplin A 17 ,[object Object],[object Object],[object Object],[object Object],[object Object]
Erythromycin 18 ,[object Object],[object Object],[object Object],[object Object],[object Object]
Combinatorial Approach of Vanomycin 33
Neocarzinostatin type compound library 34
A ‘global approach’ for the synthesis of libraries based on natural products trichostatin A and trapoxin 35
Artemisinin 19,20,21,22,23,24 ,[object Object],[object Object],[object Object]
Artemisinin (cont…) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Artemisinin (cont…) ,[object Object],[object Object],[object Object]
Paclitaxel 25,26,27 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Paclitaxel (cont…) ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],Enzyme encoding gene Source COEXPRESSION production of 1.3 mg taxadiene per liter of cell culture Taxadiene synthase T. brevifolia geranylgeranyl diphosphate synthase Erwinia herbicola isopentenyl diphosphate synthase Schizosaccharomyces pombe Deoxyxylulose 5-phosphate synthase E. coli (endogenous)
Paclitaxel (cont…) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Morphine 28,29 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Vinca Alkaloids 30,31,32 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object]
Vinca Alkaloids (cont..) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Isolation & Purification of compound from both natural source & combinatorial synthesis depends upon--Quantity, Structure & Stability Chromatograhic technique are the useful method for isolation & purification. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Structure Activity Relationship (SAR) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Biotransformation Studies ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Drug Biotransformation product Pivampicillin (Inactive) Ampicillin (Active) Phenobarbital (Active ) Hydroxyphenobarbital (Inactive) Diazepam (Tranquilizer) Oxazepam (Anticonvulsant) Isonizid (Antitubercular) Tissue acetylating intermediate
Toxicity Studies 36 ,[object Object],[object Object],[object Object],[object Object],[object Object]
Other Toxicity & Clinical Studies 36 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Scope of Drug Discovery ,[object Object],[object Object],[object Object]
references ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
References (cont..2) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
References (cont..3) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
References (cont..4) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Thank-U

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NATURAL PRODUCT LIBRARY'S ROLE IN DRUG DISCOVERY

  • 1. NATURAL PRODUCT DERIVED COMBINATORIAL LIBRARY AND IT’S SIGNIFICANCE IN DRUG DISCOVERY PROGRAMMES Presented by: ANZAR ALAM M.Pharm 2 nd Sem Pharmacognosy & Phytochemistry FACULTY OF PHARMACY JAMIA HAMDARD Presented to: Dr. (Prof.) S.H.Ansari Dean Student Welfare (DSW) JAMIA HAMDARD
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  • 4. The Long Road to a New Medicine Discovery Exploratory Development Full Development Registration Large Amounts of Candidate Medicine Synthesized Project Team and Plans Synthesis of Compounds Early Safety Studies Candidate Formulations Developed Extensive Safety Studies Screening Studies in Healthy Volunteers Phase I Candidate Medicine Tested in 3-10,000 Patients (Phase III) Studies in 100-300 Patients (Phase II) Clinical Data Analysis
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  • 25. NATURAL PRODUCT DERIVED COMBINATORIAL LIBRARY Biological Screening Startig Materials Combinatorial Synthesis Desired Activity No Desired Activity Possible Drug Candidate Combinatorial Library ( for future Drug Candidate)
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  • 37. A ‘global approach’ for the synthesis of libraries based on natural products trichostatin A and trapoxin 35
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Notes de l'éditeur

  1. 25) Idea-to-new medicine road - Full Development phase In this Full Development stage, known as Phase lll, several thousand patients with the particular disease receive the drug in carefully controlled studies to test its safety, tolerability, and efficacy. Finally, if the compound has proved its worth in all these tests, it enters the Registration phase in which the data of its entire history are compiled and analyzed in a regulatory submission. This New Drug Application, or NDA, is submitted to the FDA for review. In parallel, a Marketing Authorization Application (MAA) is filed in Europe, followed by a Japanese NDA. Only after a successful regulatory review does the candidate become a new medicine.