Abstract

SYNTHESIS AND EVALUATION OF A COUMARIN SCHIFF-BASE FOR IN VITRO ANTI-INFLAMMATORY ACTIVITY TARGETING HUMAN COX-2

Sherya Shet and Suma B. V.*

ABSTRACT

44 novel Schiff bases of aminated 4-methylumbelliferones were priorly designed and subjected to in silico evaluation of activity against human COX-2 as the target. The top-scoring compounds (as per binding affinities) were subjected to druglikeness and ADMET evaluation. Overall evaluation of the binding affinities, druglikeness and ADMET profile (especially toxicity) suggested that the derivative BVSSS10 was found to be the superior Schiff base, even when compared to the standard, Valdecoxib. Hence, BVSSS10 was synthesized, characterized and evaluated for in vitro recombinant human COX-2 inhibition assay using the COX Colorimetric Inhibitor Screening Assay Kit (Cayman Chemical Company) (n=3) which showed that at 10 μM, BVSSS10 showed a higher percentage inhibition compared to the standard, Valdecoxib (i.e. 50.30 % v/s 49.04 %). Hence BVSSS10 can undergo further structural optimization to enhance its in vitro potency or directly evaluated for in vivo anti-inflammatory activity.

Keywords: 4-methylumbelliferone, Schiff base, human COX-2, synthesis.