Structural elucidation, spectroscopic investigation, in silico docking, and in vitro cytotoxicity studies of chromone derivatives as potential anti-breast cancer agents

• Published in: Journal of molecular structure 2023-07, Vol.1284, p.135306, Article 135306
• Main Authors: Kirishnamaline, G., Magdaline, J. Daisy, Chithambarathanu, T.
• Format: Article
• Language: English
• Subjects: Chromone; Cytotoxicity; DFT; Docking; MDA-MB-231; SRB
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.135306

•Optimized geometries and spectral features of FCC and DCC molecules were analyzed.•NBO, NPA, MEP, and FMO analysis were examined via DFT approach.•Hirshfeld surface analysis was investigated to study molecular interactions.•Molecular docking studies confirmed the inhibitory activity of the title compounds.•In vitro cytotoxicity against human breast cancer cell line MDA-MB-231 was evaluated. Breast cancer is the most prevalent deadly disease affecting women globally. Discovering novel anti-breast cancer agents with better therapeutic action is more crucial in combating breast cancer. Over the past few decades, chromones are emerged as one of the promising biological scaffolds for anticancer activity. The present study reports the structural, spectral, chemical, and biological features of two chromone derivatives 6-fluoro-4-oxo-4H-chromene-3-carbaldehyde (FCC), and 6,8-dichloro-4-oxo-4H-chromene-3-carbaldehyde (DCC) by experimental techniques and quantum chemical calculations. The density functional theory (DFT) is employed to assess the optimized geometrical parameters, and spectral (FT-IR, FT-Raman, UV–Vis) features of the investigated molecules. The natural bond orbital (NBO) analysis highlights the hyperconjugative, stereoelectronic, and lone pair interactions that take place within the molecules. Moreover, Hirshfeld surface analysis signifies that O…H/H…O contacts are the strong intermolecular interactions contributing significantly to the total Hirshfeld surface. Furthermore, the in silico biological evaluation conducted on the title molecules affirmed their good pharmacological profile. Docking analysis gives deep insight into the binding affinities and the interactions with the topoisomerase II and PI3K/mTOR targets. In addition, the in vitro cytotoxicity of the title molecules evaluated on the MDA-MB-231 breast cancer cell line using the SRB assay technique revealed interesting anticancer activities of FCC (GI50 < 10 µg/ml), and DCC (GI50 = 39.3 µg/ml). Thus, the present study emphasized the therapeutic potential of chromones as anti-breast cancer agents. [Display omitted]