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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. [ABSTRACT FROM AUTHOR]

The target compound, 2-amino-4-(2,3-dichlorophenyl)-6-methoxy-4H-benzo[h]chromene -3-carbonitrile (4), was synthesized via the reaction of 4-methoxynaphthalen-1-ol (1), 2,3-dichlorobenzaldehyde (2), and malononitrile (3) in an ethanolic piperidine solution under microwave irradiation. The synthesized β-enaminonitrile derivative (4) was characterized by spectral data and X-ray diffraction. The in vitro anti-proliferative profile was conducted against five cancer cell lines and was assessed for compound 4, which revealed strong and selective cytotoxic potency. This derivative showed promising inhibition efficacy against the EGFR and VEGFR-2 kinases in comparison to Sorafenib as a reference inhibitor. Lastly, the docking analysis into the EGFR and VEGFR-2 active sites was performed to clarify our biological findings. [ABSTRACT FROM AUTHOR]

• Tricyclic 4 H -benzo[ h ]chromene and 1 H -benzo[ f ]chromene derivatives were synthesized as potential anticancer agents. • The cytotoxic activity was tested against MCF-7, HepG-2, and PC-3 cell lines. • The cell cycle analysis and apoptosis assay were reported. • The tyrosine kinase receptors EGFR and VEGFR-2 were study. A class of 4 H -benzo[ h ]chromene (4a-h) and 1 H -benzo[ f ]chromene (6a-h) derivatives linked to carboxamide/carbothioamide at the 3/2-positions were designed and synthesized with the intent of cultivating efficacious antitumor agents. The pursued benzochromenes were successfully authenticated via the employment of an array of spectral assays. Subsequently, an antiproliferative evaluation against a selected line of tumorous cells (MCF-7, HepG-2, and PC-3) were performed in-vitro for the novel benzochromenes (4a-h and 6a-g) with the superior cytotoxically-active molecules subjected to additional assessment against the non-cancerogenic cells (HFL-1 and WI-38). Compounds 4a, 6b, 6c, 6d, 6f, and 6g demonstrated high efficiency towards MCF-7, HepG-2, and PC-3 cell lines, analogous to that of Vinblastine, Doxorubicin, and feeble efficacy against normal cell lines. The inhibition activity of the selected molecules (4a, 6b, 6c, 6d, 6f, and 6g) was detected in the G2/M phase of the cell cycle, which similarly instigated the suppression of the topoisomerase I & II enzymes in order to yield this result. Additionally, the derivatives submitted for the topoisomerase inhibition appraisal were similarly subjugated to examinations regarding the inhibition of tyrosine kinase receptors EGFR and VEGFR-2, in which the results were successively contrasted against the reference kinase inhibitor Sorafenib. Lastly, the molecular docking assay of the highly potent and efficacious derivatives in correlation with the active enzymatic and kinase sites was addressed. [ABSTRACT FROM AUTHOR]