Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR ^WT , EGFR ^T790M , and EGFR ^L858R )

Abstract

Hexahydroquinoline (HHQ) scaffold was constructed and recruited for development of new series of anticancer agents. Thirty-two new compounds were synthesised where x-ray crystallography was performed to confirm enantiomerism. Thirteen compounds showed moderate to good activity against NCI 60 cancer cell lines, with GI % mean up to 74% for 10c . Expending erlotinib as a reference drug, target compounds were verified for their inhibiting activities against EGFR WT , EGFR T790M , and EGFR L858R where compound 10d was the best inhibitor with IC 50 = 0.097, 0.280, and 0.051 µM, respectively, compared to erlotinib (IC 50 = 0.082 µM, 0.342 µM, and 0.055 µM, respectively). Safety profile was validated using normal human lung (IMR-90) cells. 10c and 10d disrupted cell cycle at pre-G1 and G2/M phases in lung cancer, HOP-92, and cell line. Molecular docking study was achieved to understand the potential binding interactions and affinities in the active sites of three versions of EGFRs.

Discovery and Mechanistic Studies of Dual-Target Hits for Carbonic Anhydrase IX and VEGFR-2 as Potential Agents for Solid Tumors: X-ray, In Vitro, In Vivo, and In Silico Investigations of Coumarin-Based Thiazoles

“…A yellow prism crystal of C 22 H 18 FN 3 O 3 S was attached to a glass fiber with approximate measurements of 0.300 × 0.200 × 0.200 mm. All measurements were performed using graphite monochromated Mo–Kα radiation on a Rigaku R-AXIS RAPID diffractometer. , Compound 5e ’s crystallographic information (CCDC deposition number 2298601) was submitted to the Cambridge Crystallographic Data Center.…”

Synthesis, characterization, crystal structure and Hirshfeld surface analysis of isobutyl 4-[4-(difluoromethoxy)phenyl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

“…Recent studies have shown that these compounds are effective in cancer-related inflammatory pathways such as TGF-� (La ¨ngle et al, 2019). Additionally, they have been demonstrated to have inhibitory effects on receptors involved in cancer development, such as EGFR, or to reverse multi-drug resistance (Abo Al-Hamd et al, 2023;Shahraki et al, 2020).…”