Synthesis of benzopyrans and evaluation of cytotoxicity against ER-MCF-7 cell lines

Natural products have proved an undisputable significance in cancer therapy. In this pursuit, we used the in silico methods in design of the derivatives of the natural product-based lead scaffold-benzopyran, and synthesized and explored the inhibitory potential via in silico and in vitro anticancer screening. Computa-tional studies resulted in a prototype benzopyran structure with a great affinity towards target Estrogen receptor-alpha (ER-alpha) in breast cancer. Using benzopyran scaffold, ten probable leads were designed and opti-mized using VLife MDS ver 4.6. Molecular modeling studies of the designed scaffolds showed pi-stacking interactions with PHE404/TRP383 residues and H-bond interaction with CYS530/ARG394 residues. The bonding with amino acid residue ASP351 confirmed the designed compound's affinity towards estrogen receptor-positive (ER + ) breast cancer cell lines. Among the hits, H2 and H8 exhibited a great affinity towards the ER + breast cancer. In addition, the designed compounds exhibited the minimum pharma-cophoric features required to act like the standard drug tamoxifen used clinically as an estrogen receptor antagonist. Derivatives of H8 were further optimized and compounds S1-S14 were synthesized. Synthe-sis was carried out using Radley's six-station reactor. In a two-step reaction, 1,4-benzopyrone aldehyde was used as a starting material to afford an acid derivative, which was reacted with different L-amino acids to obtain the benzopyran derivatives. Results of the in vitro anticancer screening using ER + MCF-7 cell lines revealed that the compounds S7 and S13 exhibited highest cytotoxicity. This study could be a great platform to explore and develop novel molecules from natural sources in the management of breast cancer. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study utilized in silico methods to design derivatives of the natural product-based lead scaffold-benzopyran and explored their inhibitory potential in cancer therapy through in silico and in vitro screening. The designed compounds exhibited a high affinity towards estrogen receptor-alpha in breast cancer and showed promising cytotoxicity against ER + breast cancer cell lines.