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

Abstract

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 ¹H NMR, ¹³C 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 IC₅₀, respectively. This activity was found close to indomethacin COX-2 inhibition measured as 7.4 μM IC₅₀. Rest of the compounds (1, 3-9) showed 10.4-28.1 μM IC₅₀ on COX-2 and 17.0-35.6 μM IC₅₀ 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.

Keywords: anti-inflammatory; cox-1; cox-2; cylooxygenase; pyrazolone.