SUMMARY
Novel dithioic acid derivatives have been synthesized from 3 different natural acids having marked anti-inflammatory activities including ferulic acid, cinnamic acid and salicylic acid. The structures of the new compounds were established on the basis of IR, 1H NMR and mass spectral data. In silico molecular analysis of different dithioic acid analogues of natural acids were done, and the compounds which obeyed Lipinski's rule of five were taken for computing molecular descriptors. Docking studies were carried out against target, human TNF-? converting enzyme (TACE). Out of the seventeen analogues docked, compound 1b, 2b and 3b exhibited minimum glide score and were taken out for wet laboratory synthesis and validations. Compound 1b ({5-[(E)-2-(4-hydroxy-3-methoxyphenyl) ethenyl]-1, 3, 4-thiadiazol-2-yl}carbamodithioic acid) was screened for in vitro anti-TNF-? study, and compounds 1b, 2b and 3b for in vivo anti-inflammatory activity. In vitro specific TNF-? inhibitory activity of the ferulic acid analogue (1b) was evaluated using Reverse transcriptase- polymerized chain reaction. In vitro and in vivo anti-inflammatory activity was also evaluated using the HRBC membrane stabilization method and carrageenan induced rat paw edema method and compared with standard drug (diclofenac sodium). Among all derivatives 1b (ferulic acid derivative) showed maximum percentage inhibition (60.09%) while the remaining compounds showed moderate inhibition.