1571842-04-0Relevant articles and documents
Indole based peptidomimetics as anti-inflammatory and anti-hyperalgesic agents: Dual inhibition of 5-LOX and COX-2 enzymes
Singh, Palwinder,Prasher, Parteek,Dhillon, Parvirti,Bhatti, Rajbir
, p. 104 - 123 (2015)
The indoles bearing a tosyl group at N-1 and a dipeptide substituent at C-3 were screened for anti-inflammatory and anti-hyperalgesic activities. Some of the compounds made significant reduction in the dextran induced swelling and capsaicin induced pain in the albino mice. About 95% reversal in capsaicin induced pain occurred in the presence of 5 mg kg-1of compound 7b, 7d and 7h while diclofenac showed 90% reversal when its 10 mg kg-1 dose was used. In order to examine the mode of action of these compounds; COX-1, COX-2 and 5-LOX enzyme immunoassays were performed. The IC50 of compound 7b for COX-2 and 5-LOX were in the nM range: 5-LOX, IC50 Combining double low line 2.0 nM; COX-2, IC50 Combining double low line 6.3 nM, selectivity for COX-2 over COX-1 was 351. The interactions of the compounds with COX-2 and 5-LOX were supported by the physical parameters including Ki, Ka and δ G. The most potent compounds 7b, 7d and 7h showed no toxicity to the animals and were identified as the promising leads for anti-inflammatory drugs.
Lead modification: Amino acid appended indoles as highly effective 5-LOX inhibitors
Prasher, Parteek,Pooja,Singh, Palwinder
, p. 1642 - 1648 (2014/03/21)
N-1 tosyl indoles carrying amino acid as a part of C-3 substituent are identified with considerable 5-LOX inhibitory activities. On the basis of enzyme inhibitory activities and log P, it is found that these compounds are more suitable to use as ester prodrugs. In addition to the significant Ka and Ki for 5-LOX, advantageously the compounds under present investigation do not affect the viability of the cell. The experimental results were also supported by molecular docking of compounds in the active site of 5-LOX.
