Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid

CHANNAR, PERVAIZ ALI; SAEED, AAMER; LARIK, FAYAZ ALI; BATOOL, BAKHTAWAR; KALSOOM, SAIMA; HASAN, M.M.; ERBEN, MAURICIO F.; EL-SEEDI, HESHAM R.; ALI, MUSRAT; ASHRAF, ZAMAN

BIOORGANIC CHEMISTRY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2018 vol. 79 p. 293 - 300

0045-2068

Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC50 = 1.568 ± 0.01 µM) showed relatively better potential compared to reference kojic acid (IC50 = 16.051 ± 1.27 µM). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (−6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 Å which might be responsible for higher activity compared to Kojic acid.