183. 3 : 4-Benzoxanthens. Part III. The synthesis and oxidation of 5-, 6-, 7-, and 8-methyl-3 : 4-benzoxanthen

Gindy, Munir; Dwidar, Ibrahim M.

doi:10.1039/jr9530000893

Cited by 2 publications

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“…All synthesised compounds were purified by column chromatography and characterized by 1 H-NMR, 13 C-NMR, and high-resolution electron impact-mass spectrometry (HRMS). The melting point of known compounds ( 2a , 2b and 2f ) were compared to that of previously reported data [ 35 , 36 , 37 , 38 ]. Prior to assays, the purity of synthesized compounds was confirmed to be greater than 95% based on their respective HPLC profiles ( Supplementary Materials ).…”

Section: Resultsmentioning

confidence: 99%

In-Vitro and In-Silico Evaluations of Heterocyclic-Containing Diarylpentanoids as Bcl-2 Inhibitors Against LoVo Colorectal Cancer Cells

et al. 2020

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In the present study, we investigated the in-vitro anti-cancer potential of six diarylpentanoids against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, SW620, LoVo, HT29, NCI-H508, RKO, and LS411N cells. Structure–activity relationship study suggested that the insertions of tetrahydro-4H-thiopyran-4-one and brominated phenyl moieties are essential for better cytotoxicity. Among the evaluated analogs, 2e has been identified as the lead compound due to its low IC50 values of approximately 1 µM across all cancer cell lines and high chemotherapeutic index of 7.1. Anti-proliferative studies on LoVo cells showed that 2e could inhibit cell proliferation and colony formations by inducing G2/M cell cycle arrest. Subsequent cell apoptosis assay confirmed that 2e is a Bcl-2 inhibitor that could induce intrinsic cell apoptosis by creating a cellular redox imbalance through its direct inhibition on the Bcl-2 protein. Further molecular docking studies revealed that the bromophenyl moieties of 2e could interact with the Bcl-2 surface pocket through hydrophobic interaction, while the tetrahydro-4H-thiopyran-4-one fragment could form additional Pi-sulfur and Pi-alkyl interactions in the same binding site. In all, the present results suggest that 2e could be a potent lead that deserves further modification and investigation in the development of a new Bcl-2 inhibitor.

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