A Simplistic Approach for Preparation of Alkylidenemalononitrile Derivatives: Characterization, In silico Studies, Quantum Chemical Evaluation, Molecular Docking, and In vitro Biological Activity Evaluation

A new and efficient green grinding-based catalyst free Knoevenagel condensation of aldehydes/ketones and malononitrile for the rapid preparation of twelve malononitrile derivatives (C1-C12) is proposed. Characterization of the derivatives was done by H-1 NMR, C-13 NMR, IR, elemental and mass spectral analyses. Quantum chemical calculations were performed by DFT/B3LYP/6-31G(d,p) method. The experimental and theoretical spectra were found to be in good agreement with each other. Natural bond order (NBO) calculations were also performed to calculate the natural atomic charges at atomic sites. The present study also involved study of the intramolecular charge transfer (ICT) interactions and the non-linear optical (NLO) properties. Critical drug character assessment parameters like metabolic transformation, druglikeness, ADMET (absorption, distribution, metabolism and excretion) and toxicological analyses of the synthesized malononitrile derivatives were also performed. Molecular docking studies were performed against two target proteins viz. tyrosine-protein kinase (HCK) and ribonucleoside diphosphate reductase (RR). The synthesized malononitrile derivatives were also evaluated for their anticancer activity against the triple negative breast cancer (TNBC) cell line (MDA-MB-231) while their antibacterial potential was tested against S. aureus and E. coli. (C) 2020 Elsevier B.V. All rights reserved.