QSAR, docking and in vitro studies for anti-inflammatory activity of cleomiscosin A methyl ether derivatives.

A series of five (6a-8b) novel polyhalogenated derivatives and an interesting ester (9a) derivative have been synthesized from cleomiscosin A methyl ether. All the six derivatives were subjected to in silico QSAR modeling and docking studies and later the predicted results were confirmed through in vitro experiments. QSAR modeling results showed that compounds 6a and 9a possessed anti-inflammatory activity comparable or even higher than diclofenac sodium. Docking results revealed that compounds 9a and 6a showed very good anti-inflammatory activity due to low docking energies of viz., IL6 (-92.45 and -81.993 kcal mol(-1)), TNF-α (-94.992 and -69.235 kcal mol(-1)) and IL1β (-67.462 and -65.985 kcal mol(-1)). Further all the six novel derivatives were subjected for in vitro anti-inflammatory activity using primary macrophages cell culture bioassay system. At the initial doses of 1 μg/ml and 10 μg/ml, the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were quantified from cell culture supernatant using enzyme linked immunosorbent assay (ELISA). The in vitro effect of 6a-9a on cell viability in mouse peritoneal macrophage cells isolated from mice was evaluated using MTT assay. The in silico and in vitro data suggested that all the derivatives might be considered as potential anti-inflammatory drug-like molecules.