Discovery of benzochromene derivatives first example with dual cytotoxic activity against the resistant cancer cell MCF-7/ADR and inhibitory effect of the P-glycoprotein expression levels

Abstract

A series of 1H-benzo[f]chromene moieties (4a–z) were synthesised under Ultrasonic irradiation and confirmed with spectral analyses. Derivative 4i solely possessed an X-ray single crystal. The anti-proliferative efficacy of the desired molecules has been explored against three cancer cells: MCF-7, HCT-116, and HepG-2 with the cytotoxically active derivatives screened against MCF-7/ADR and normal cells HFL-1 and WI-38. Furthermore, compounds 4b–d, 4k, 4n, 4q, and 4w, which possessed good potency against MCF-7/ADR, were tested as permeability glycoprotein (P-glycoprotein [P-gp]) expression inhibitors. The attained data confirmed that 4b–d, 4q, and 4w exhibited strong expression inhibition against the P-gp alongside its cytotoxic effect on MCF-7/ADR. The western blot results and Rho123 accumulation assays showed that compounds 4b–d, 4q, and 4w effectively inhibited the P-gp expression and efflux function. Meanwhile, 4b–d, 4q, and 4w induced apoptosis and accumulation of the treated MCF-7/ADR cells in the G1 phase and 4k and 4n in the S phase of the cell cycle.

Graphical Abstract

Keywords:

• Ultrasound synthesis
• 1H-Benzo[f]chromenes
• antitumor activity
• MCF-7/ADR
• P-glycoprotein
• western blot
• cell cycle arrest
• SAR

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The authors would like to express gratitude to the Deanship of Science Research at King Khalid University, Saudi Arabia for funding this work through General Research Project under Grant Number [RGP.1/245/43] and also, to Malak T. Mahmoud for editing and revising the manuscript.