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 1 H -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.

New cyclic glycolipids from Silene succulenta promote in vitro MCF-7 breast carcinoma cell apoptosis by cell cycle arrest and in silico mitotic Mps1/TTK inhibition

“…Finally, using a 488 nm laser excitation and FL2 of a ow cytometer, the intensity of PI uorescence was measured. 52 3.2.4. Annexin V-FITC apoptosis.…”

Targeted potent antimicrobial and antitumor oxygen-heterocyclic-based pyran analogues: synthesis and computational studies

“…It's also critical to keep in mind that the 1-position in compound 4a-q , is a chiral center 8 and that each reaction was carefully regulated using the TLC method.…”

“…Similarly, 1 H -benzo[ f ]chromene derivatives are regarded as promising lead candidates for anticancer drug development. For example, 9-hydroxy/methoxy of 1 H -benzo[ f ]chromene derivatives ( N ) effective cytotoxic activity on MCF7/ADR, P -Glycoprotein inhibitors, Cell cycle arrest and apoptosis effects 7 , 8 , 1 H -benzo[ f ]chromene derivatives and 8-bromo/methoxy derivative of 1 H -benzo[ f ]chromenes (O) exhibited c-Src kinase inhibitory and proapoptotic activities 24 , 25 . A series of 1-substituted aryl-2-(1 H -tetrazol-5-yl)-1 H -benzo[ f ]chromene-3-amines (P) derivatives 27 , some derivatives of 3,5-diamino and 3-amino of 1 H -benzo[ f ]chromene-2-carbonitrile (Q) , have been reported to exhibit cytotoxic and apoptotic effects against a variety of human cancer cell lines 17 , 28 , 29 .…”

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study

“…The DFT/B3LYP/6311G** was applied to compute the energy gap “ Δε ” for 1 – 8 molecules using distribution shapes along the following orbitals: HOMO “ donating electrons ” and LUMO “ accepts electrons ” ( Figure 4 ). The Δε was able to determine a molecule’s kinetic stability before simulating its chemical reactivity [ 37 ]. Imidazo[4,5-b]pyridine with a high Δε has a hardness quality “η” and is a good nucleophile; the pyridine system with a low Δε is a soft hybrid and an excellent electrophile ω ( Table 2 ).…”