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Design, Synthesis, Preliminary Pharmacological Screening Of Some Indolizine Derivatives For Antiinflammatory Activity | 37500
Clinical Pharmacology & Biopharmaceutics
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A need for better anti-inflammatory agents with lesser side effects especially less ulcer forming capability is prevalent. The
imidazo[1,2-a]pyridine derivatives possesses 5-LOX inhibition potential. A bio-isosteric replacement gave bicyclic nucleus-
Indolizine and its derivatization resulted in compounds which showed anti-inflammatory activity. These derivatives were synthesised
using 1,3-dipolar cycloaddition of heterocyclic N-ylides with electron deficient alkenes. The chemical structure of derivatives were
confirmed by means of IR, 1H-NMR and elemental analysis. Five compounds (IND004, IND005, IND006, IND007 and IND008)
showed significant inhibition of edema in carrageenan and arachidonic acid induced paw edema model at a dose equimolar to
diclophenac sodium. Ulcerogenic study results revealed less ulcerogenic liability of IND004 compared to standard diclophenac
sodium in rats. The in silico docking simulation confirmed their consensual interaction with the key binding site residues His-550,
Phe-610 and Glu-614 of 5-LOX corroborating the outcomes of in vivo evaluation studies. These indolizine analogs were promising
for the use as anti-inflammatory agents for acute inflammatory disorders especially with low toxic effects.
Pavan Srivastava has completed his MPharm from Nirma University and is purusing PhD under the supervision of Professor S K Shrivastava from Indian Institute of Technology (Banaras Hindu University) Varanasi, India. He had also worked in the R&D centre of Piramal Healthcare at Ahmedabad for 1.2 years as a Research Associate. His current research interests are Medicinal Chemistry for the development of novel compounds to treat the neurogenrative disorders and anti-inflammatory agents.