DRUG DESIGN GROUP

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DRUG DESIGN GROUP
AT DEPARTMENT OF CHEMISTRY UNIVERSITY OF
PUNE PUNE 411 007 TEL [phone] EXT.
36 FAX [phone] E-MAIL
sbpadhye_at_chem.unipune.ernet.in
Professor Subhash Padhye
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• RESEARCH AREAS
• Targeted Drugs for
• Hormone Responsive cancers (Breast, Prostate and
  Skin).
• Antitubercular Drugs.
• Antimalarial Drugs.
• New Selective Antiinflammatory drugs (for
  therapeutic applications to cancer as well !!!).
• Biosensors for clinical diagnostics.

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        DNA Structure

• Who spoils our Life ? Is it Oxygen?
• A human being consumes about 800 litres of O2 per
  day 5 of it gets converted into radical
  species(superoxide, peroxide, nitric oxide,
  hydroxyl etc.) which can damage proteins, fats,
  DNA etc.
• Body defends against these through antioxidant
  substances like enzymes, ?-carotene, vitamin E
  and C etc. which can prevent diseases like
  cancer, cataract, diabetes, arthritis etc.
• Balanced diet, appropriate exercises and tranquil
  mind can increase life span and quality of life.

Free radicals
Beta-carotene combines with free radicals so they
can no longer damage molecules like DNA
Deactivated free radical
Free radicals can damage DNA and other molecules
hyperbio_at_mit.edu
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Levels of Antioxidant Enzymes Vs. Life Span

• Accumulation of the oxidation products of fatty
  acids like pentane, malondialdehyde, lipofuschin
  also correlates with life-spans of the species.
• For example, a dog accumulates lipofuschin in the
  heart 5 times faster than humans and hence
  average life of a dog is about 12 years whereas
  those of humans is about 60 years.

Man
Chimp
Gorilla
Baboon
Lemur
Housemouse
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Free radicals trigger the synthesis of
Prostaglandins and Prostacyclins PGI2 starting
from Phospholipids which leads to inflammatory
disorders.
Phospholipids
Arachidonic acid
COX-2
COX-1
NSAIDs
Inhibitors include Aspirin,Ibuprofen
Indomethacin Inhibition may lead to Gastric
ulcers, Kidney damages
Inhibitors include Nimesulide, NS-398. No known
side-effects
Prostaglandins
Prostaglandins
Pain is caused by the effects of these
prostaglandins which are released in the
inflammatory process.
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TOXICITY OF NSAIDs
SAFEST
DRUG NAME
DOSAGE RANGE
ASA
325-975 mg
IBUPROFEN
200-600 mg
DICLOFENAC
50/200 mg
NAPROXEN
125-500 mg
SULINDAC
150-200 mg
TOLMETIN
200-600 mg
KETOPROFEN
50-100 mg
INDOMETHACIN
25-50 mg
PIROXICAM
10-20 mg
MOST TOXIC

MARKET VALUE OF NSAIDS
Market value of common NSAIDs was estimated to
be 30 Million dollars in 1998 !!
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OUR WORK DEALS AT TWO LEVELS
Creating new COX-2 inhibitors which are effective
in low doses.
Control
Producing oral drugs which can scavenge toxic
radicals (because enzymes are ineffective by
oral/I.P. routes.
Nimesulide
Our compound
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FURTHER BENEFITS OF NEW DRUGS Some of the new
drugs have been found effective in
preventing/treating cancers. (Ref. National
Cancer Institute Workshop at Rockville,
Maryland(USA) on 8 January 2001)
Both mice received transplants of human cancer
cells,but treatment of bottom animal with an
NSAID greatly slowed the growth of the cells.