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. 2024 Apr 29;14(1):9866.
doi: 10.1038/s41598-024-59166-5.

Synthesis, molecular docking studies and biological evaluation of N-(4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl) benzamides as potential antioxidant, and anticancer agents

Sumalatha Jorepalli  1   2 , Sreedevi Adikay  3 , Radha Rani Chinthaparthi  4 , Chandra Sekhar Reddy Gangireddy  4 , Janardhan Reddy Koduru  5 , Rama Rao Karri  6
Affiliations

Synthesis, molecular docking studies and biological evaluation of N-(4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl) benzamides as potential antioxidant, and anticancer agents

Sumalatha Jorepalli et al. Sci Rep. .

Abstract

A series of novel chromone derivatives of (N-(4-oxo-2-(trifluoromethyl)-4H-chromen-6-yl) benzamides) were synthesized by treating 7-amino-2-(trifluoromethyl)-4H-chromen-4-one with K2CO3 and/or NaH, suitable alkyl halides and acetonitrile and/or 1,4-dioxane. The obtained products are in high yields (87 to 96%) with various substituents in short reaction times with no more by-products and confirmed by FT-IR, 1H, and 13C-NMR Spectral data. The in vitro cytotoxic activity was examined against two human cancer cell lines, namely the human lung adenocarcinoma (A-549) and the human breast (MCF-7) cancer cell line. Compound 4h showed promising cytotoxicity against both cell lines with IC50 values of 22.09 and 6.40 ± 0.26 µg/mL respectively, compared to that of the standard drug. We also performed the in vitro antioxidant activity by DPPH radical, hydrogen peroxide, NO scavenging, and total antioxidant capacity (TAC) assay methods, and they showed significant activities. The possible binding interactions of all the synthesized chromone derivatives are also investigated against selective pharmacological targets of human beings, such as HERA protein for cytotoxic activity and Peroxiredoxins (3MNG) for antioxidant activity which showed closer binding free energies than the standard drugs and evidencing the above two types of activities.

Keywords: Antioxidant activity; Chromones; Cytotoxic activity; Molecular docking study.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Scheme 1
Scheme 1
Synthesis of the N-(4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl) benzamides (4a-k).
Figure 1
Figure 1
Possible and tentative SAR of compound 4h as a model for the titled compounds.
Figure 2
Figure 2
Photomicrographs of human lung adenocarcinoma (A549) cells treated with the test compounds 4h, 4b, and 4e at concentrations of 12.5, 25, 50, and 100 µg/mL after 48 h of drug exposure (magnification 10X).
Figure 3
Figure 3
Changes in cell viability during the treatment with title compounds and control in MCF-7 cell lines.
Figure 4
Figure 4
Diagrammatic representation of 3D modelled binding modes of the compounds and standard with the binding domain of Human estrogen receptor alpha protein.
Figure 4
Figure 4
Diagrammatic representation of 3D modelled binding modes of the compounds and standard with the binding domain of Human estrogen receptor alpha protein.
Figure 5
Figure 5
2D binding domains of lead compounds against 3MNG protein.
Scheme 2
Scheme 2
Pictorial representation of the simple condensation reaction of chromone derivative (1).
Figure 6
Figure 6
3D structures of (a) HERA and (b) Doxorubicin.
Figure 7
Figure 7
Structures of the target protein and reference compounds.
See this image and copyright information in PMC

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