Pyrimidine Tethered Pyrazoles: Synthesis, Biological, and Molecular Docking Studies

Abstract

A series of pyrimidine integrated pyrazoles (5a?5g) has been synthesized in good yields from aryl hydrazines and aralkyl ketones through a protocol of multi-steps such as condensation/imine formation, cyclization/Vilsmeier-Haackreaction, and Knoevenagelcondensation and characterized through physical and spectral techniques. 2,2-diphenylpicrylhydrazyl radical scavenging evaluation revealed that the chemical entity possessing para-fluoro substituent on the aromatic unit tethered at the carbon of pyrazole scaffold 5g exerted the highest activity among the investigated ones. Of the results of cytotoxicity evaluation utilizing AsPC1, BxPC3, SW1990 (pancreatic cancer cells), the chemical entity possessing ortho-chlorosubstitient on the aryl unit integrated at carbon of pyrazole scaffold 5b exhibited superior activity. Besides, the molecular docking studies of the ortho-chloroaryl group possessing chemical entity 5b with BCL-2 (B-cell lymphoma 2) displayed significant binding affinity (-9.1 kcal mol-1). In addition, pharmacokinetic as well as prediction of drug-likeness for all the molecular hybrids 5a?5g have been evaluated using SwissADME tool and all the chemical entities are in good agreement of Lipinski rule with no violation.. KEYWORDS :Cytotoxicity, Molecular docking, Pyrazoles, Pyrimidines, Radical scavenging, SwissADME.