Management of Pain and Inflammation Pain affects a large population worldwide.

1. PHARMA TECHNOLOGIES NEW ANTIOXIDANTS TO COMBAT INFLAMMATORY DISORDERS AND CANCERS Dept. of Chem . UoP Prof. Subhash Padhye • Management of Pain and Inflammation • Pain affects a large population worldwide. • Potentially dangerous stimuli causing pain need to be reported immediately for our well-being. • Management of pain by traditional therapies involve use of NSAIDs, opoids and antidepressants. • These have low therapeutic indexes and undesirable side effects. They are often relatively ineffective in treating chronic pain. • Need to evolve new molecules which are selective, possess high therapeutic index and few side-effects, if any.

2. PHARMA TECHNOLOGIES NEW ANTIOXIDANTS TO COMBAT INFLAMMATORY DISORDERS AND CANCERS Dept. of Chem . UoP Prof. Subhash Padhye Arachidonic acid Free radicals COX-1 COX-2 Inhibitors include: Aspirin,Ibuprofen & Indomethacin Inhibition may lead to Gastric ulcers, Kidney damages Inhibitors include Nimesulide, NS-398. No known side-effects NSA ID’s Prostaglandins Prostacyclins Pain is caused by the effects of these prostaglandins which are released in the inflammatory process.

3. PHARMA TECHNOLOGIES Dept. of Chem . UoP Prof. Subhash Padhye NEW ANTIOXIDANTS TO COMBAT INFLAMMATORY DISORDERS AND CANCERS OUR WORK DEALS AT TWO LEVELS Control Nimesulide Creating new COX-2 inhibitors which are effective in low doses. Ourcompound Producing oral drugs which can scavenge toxic radicals (because enzymes are ineffective by oral/I.p. routes.

4. PHARMA TECHNOLOGIES NEW ANTIOXIDANTS TO COMBAT INFLAMMATORY DISORDERS AND CANCERS Dept. of Chem . UoP Prof. Subhash Padhye Conjugate of L1 Conjugates of L2 & L3 The IC50 values in M of the curcumin derivatives and their metal complexes (IC50 for native SOD = 4x10-8 M ; For [ Cu2(bpzbiap)Cl3]= 2.55x10-7M Ref: Reedijk et.al, IC,36 (1997)1168

5. PHARMA TECHNOLOGIES NEW ANTIOXIDANTS TO COMBAT INFLAMMATORY DISORDERS AND CANCERS Dept. of Chem . UoP Prof. Subhash Padhye Both Mice received Transplant of human Cancer cells but treatment of the Bottom Animal with an NSAID greatly slowed the growth of the cells

6. PHARMA TECHNOLOGIES A. R. I Prof. Sabita Dey Ratnakar Chitte A NEW THROMBOLYTIC ENZYME FOR ACUTE MYOCARDIAL INFARCTION Quchterlony test of Actinokinase Clot dissolution time -------Plasmin --- ---- Streptokinase -------- Urokinase ------ Actinokinase

7. PHARMA TECHNOLOGIES Modern Cancer therapy Search for Immunomodulators • Sham Diwanay • Dept. of Microbiology, • Abasaheb Garware College, • Pune • Dr. Bhushan Patwardhan • School of Health Sciences, • University of Pune, Pune Immunomodulation • Concept and Definition: Immunomodulators are Biological Response Modifiers (BRM), used to treat cancer, exert their anti-tumor effects by improving host defense mechanisms against tumor (Encyclopedia Britannica). • Immunostimulation in drug-induced immunosuppression and immunosuppression in experimental hyper-reactivity model by the same preparation can be said to be true immunomodulation.

8. PHARMA TECHNOLOGIES Modern Cancer therapy Search for Immunomodulators • Sham Diwanay • Dr. Bhushan Patwardhan Ashwagandha Gulwel Shatavari

9. PHARMA TECHNOLOGIES Modern Cancer therapy Search for Immunomodulators • Sham Diwanay • Dr. Bhushan Patwardhan

10. PHARMA TECHNOLOGIES Modern Cancer therapy Search for Immunomodulators • Sham Diwanay • Dr. Bhushan Patwardhan • Treatment with few selected test preparations resulted in : • Immunostimulatory activity in tumor-free animals receiving or not receiving anticancer drugs. • Protection from toxic side effects viz. myelo, immuno- suppression without compromising or interference with anticancer activity and this activity was dose dependent. • Treatment with these candidate drugs will be important in development of supportive / adjuvant treatment to cancer therapy to avoid untoward effects.