Facile synthesis of thiophene-embedded Baicalein via oxidative cyclization and anticancer activity against ovarian cancer cells via inhibiting PI3K/MTOR signaling pathway: in-vitro and in-silico study

Abstract

This study illustrated the synthesis of a thiophene-embedded Baicalein (BAC) conjugate through the formation of a chalcone backbone, accomplished by refluxing hydroxyl-acetophenone with 5-nitrothiophene-2-carbaldehyde in the presence of piperidine. The BAC conjugate (5,6,7-trihydroxy-2-(5-nitrothiophen-2-yl)-4H-chromen-4-one) was obtained through the oxidative cyclization of the previously synthesized chalcone using DMSO/I2. The structure of BAC was determined by FTIR, 1H-NMR, 13C-NMR, mass spectrometry, and elemental analysis. The impact of BAC on SKOV-3 ovarian cancer cells was assessed via several pharmacological assays, including viability, apoptosis, migration, invasion, and cell cycle analysis. RT-qPCR analysis was performed to assess the impact of BAC on the mRNA levels of Bcl2, Bax, PI3K, Akt, and mTOR. BAC underwent docking analysis utilizing the 3D crystal structure of PI3K. The results indicate that BAC decreases cell viability, migration, invasion, and induces cell cycle arrest at the G2/M phase in SKOV-3 cells in a concentration-dependent manner. The Annexin FITC assay demonstrated the activation of apoptosis by increasing Bax expression and decreasing Bcl2 expression. The mRNA expression of PI3K, Akt, and mTOR was considerably suppressed relative to the untreated control, potentially through interactions with Trp201, Gln291, Leu657, Arg690, Phe694, and Arg849 of PI3K.

Keyword: Cell-viability, Apoptosis, Migration, Cell-cycle, RT-qPCR, Docking

Bull. Chem. Soc. Ethiop. 2025, 39(2), 367-379.                                                             

DOI: https://dx.doi.org/10.4314/bcse.v39i2.14