QM study and conformational analysis of an isatin Schiff base as a potential cytotoxic agent

Abstract

Isatin is an important compound from the biological aspect of view. It is an endogenous substance and moreover; various pharmacological activities have been reported for isatin and its derivatives. In-vitro cytotoxic effects of the prepared isatin Schiff bases toward HeLa, LS180 and Raji human cancer cell lines has been reported in our previous work. 3-(2-(4-nitrophenyl)hydrazono) indolin-2-one was found to be the most potent one among the studied compounds (IC(30) =12.2 and 21.8 μM in HeLa and LS-180 cell lines, respectively). Obtained biological data could be well interpreted using docking binding energies toward vascular endothelial growth factor receptor (VEGFR-2); a key anticancer target being biologically investigated against various isatin derivatives. In the present work, quantum mechanical (QM) method including functional B3LYP in association with split valence basis set using polarization functions (Def2-SVP) was used to estimate individual ligand-residue interaction energies for the docked 3-(2-(4-nitrophenyl)hydrazono) indolin-2-one into VEGFR-2 active site. Results were further interpreted via calculated polarization effects induced by individual amino acids of the receptor active site. A fairly good correlation could be found between polarization effects and estimated binding energies (R(2) =0.7227). Conformational analysis revealed that 3-(2-(4-nitrophenyl) hydrazono) indolin-2-one might not necessarily interact with the VEGFR-2 active site in its minimum energy conformation.

Schiff Bases: A Versatile Pharmacophore

“…Schiff bases form an important class of the most widely used organic compounds and have a wide variety of applications in many fields including analytical, biological, and inorganic chemistry. Schiff bases have gained importance in medicinal and pharmaceutical fields due to a broad spectrum of biological activities like anti-inflammatory [4][5][6][7], analgesic [5][6][7][8], antimicrobial [9,10], anticonvulsant [11], antitubercular [12], anticancer [13,14], antioxidant [15], anthelmintic [16], and so forth. The nitrogen atom of azomethine may be involved in the formation of a hydrogen bond with the active centers of cell constituents and interferes in normal cell processes [17,18].…”

3-Hydrazinoindolin-2-one derivatives: Chemical classification and investigation of their targets as anticancer agents

“…indolinone NH with Glu915 and two oxygen atoms of nitro group with Arg1049 and Asn921 (Figure 12) [35]. revealed that distal hydroxyl group on the ring D is critical for activity.…”

Synthesis of Schiff base Metal Complexes with Motivating Scavenging Potential Studies

“…The medicinal utilization and applications Schiff bases and their metal complexes are of growing clinical and commercial significance. Schiff bases were selected significance in medical and pharmacological domain due to an expansive range of biological activities such as anti-inflammatory, 1,2 analgesic, 3,4 antimicrobial, 5 antispasmodic, 6 tuberculosis, 7 anticancer, 8 antioxidants, 9,10 anthelmintic. 11,12 The antioxidant performance of N-amino quinoline-2-one metal complexes versus, hydrogen peroxide radicals was not described.…”