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

AbstractA 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

Synthesis, in vitro cytotoxicity activity against the human cervix carcinoma cell line and in silico computational predictions of new 4-arylamino-3-nitrocoumarin analogues

Halawa AH, Eliwa EM, Hassan AA, et al. Synthesis, in vitro cytotoxicity activity against the human cervix carcinoma cell line and in silico computational predictions of new 4-arylamino-3-nitrocoumarin analogues. JOURNAL OF MOLECULAR STRUCTURE. 2020;1200: UNSP 127047.A new series of 4-arylamino-3-nitrocoumarin analogues (4-18) have been synthesized and characterized by sophisticated spectroscopic techniques (H-1 NMR, C-13 NMR) and mass spectrometry. All the new synthesized compounds were evaluated for their in vitro cytotoxic activity against the human cervix carcinoma cell line (KB-3-1) using resazurin assay with (+)-griseofulvin as the positive control (IC50 = 19 mu M). Among them, thiazolidinylidene derivative 17a that bearing malononitrile unit displayed the best cytotoxic potency with IC50 value of 21 mu M. Also, in silico docking simulation studies were conducted on human DNA topoisomerase 1 (Top1) (PDB: 1T8I) to explore and interpret the interaction pattern between the selected compounds and target enzyme as well confirm the acquired cytotoxicity results. In addition to the above, in silico predictions of physicochemical properties, ADME (absorption, distribution, metabolism and excretion) parameters, oral toxicity and indication of toxicity targets were implemented for some title compounds. (C) 2019 Published by Elsevier B.V