Novel benzofurane-pyrazole derivatives with anti-inflammatory, cyclooxygenase inhibitory and cytotoxicity evaluation.

Novel benzofurane-pyrazolone hybrids have been synthesized for evaluating their anti-inflammatory and cytotoxic properties. 4-(2-chloroacetyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one were reacted with α-hydroxy aldehyde or α-hydroxy ketone derivatives to obtain nine novel pyrazolone derivatives. Structures were successfully elucidated by 1 H NMR, 13 C NMR, IR and HRMS. Enzyme inhibitory activity was measured on cyclooxygenases (COXs) as considered to address anti-inflammatory activity. Compound 2 showed the highest activity on both COX-1 and COX-2 subtypes with 12.0 μM and 8.0 μM IC 50 , respectively. This activity was found close to indomethacin COX-2 inhibition measured as 7.4 μM IC 50 . Rest of the compounds ( 1 , 3 - 9 ) showed 10.4-28.1 μM IC 50 on COX-2 and 17.0-35.6 μM IC 50 on COX-1 (Compound 1 has no activity on COX-1). Tested compounds ( 1-9 ) showed activity on NO production. Only compound was the 4 , which showed a low inhibition on IL-6 levels. Cell viability was up to 60% at 100 μM for all compounds ( 1 - 9 ) on RAW 264.7 and NIH3T3 cell lines, thus compounds were reported to be noncytotoxic.