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Novel 5-(4-bromophenyl)-1,3-oxazole derivatives: Synthesis, Characterization, Docking and Evaluation of in vitro Anticancer Activity
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| Author:
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PRADEEP GOLANI, SUNIL KUMAR SHAH, C.K.TYAGI
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| Abstract:
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Aromatase is one of the important target for drugs that interfere with production of estrogen in the treatment of estrogen receptor positive breast cancer. Therefore the discovery of novel aromatase inhibitors that can kill the growth of cancer cells selectively with minimal toxic effects on normal healthy cells is desirable. In the present study, novel 5-(4-bromophenyl)-1,3-oxazole derivatives were synthesized, characterized and screened for their biological effect. A series of novel 5-(4-bromophenyl)-1,3-oxazole derivatives OXZ-1 to 12 were docked by Auto Dock tool to evaluate their aromatase inhibition. All the derivatives were synthesized by using versatile and convenient route. Spectroscopic techniques have characterized the synthesized compounds in order to validate their structures. A total of 12 compounds were synthesized and evaluated for their in-vitro aromatase inhibitory activity and all derivatives were tested to assess their cytotoxic effect against breast cancer cell lines (MCF-7). The in vitro cytotoxic activity of the synthesized compounds was determined by MTT assay using MCF7 cell lines. Docking parameters showed that polar (M303, A307 and T310) and non-polar (A306, M311, F430 and A443) residues were essential for interaction with the aromatase inhibitors. In comparison with the vehicle-treated control Letrozole (IC50 15.83µM), aromatase inhibition activity of synthesized compounds was measured. OXZ-9 demonstrated excellent inhibition with an IC50 value of 14.8µM at 50 percent maximal inhibitory concentration. In vitro cytotoxicity of oxazole derivatives was conducted against MCF7 cell lines by using Cisplatin (IC50 12.46µM) as reference and potent cytotoxic activity was observed for the compounds OXZ-9, OXZ-11, OXZ-8, OXZ-4 and OXZ-3 and their IC50 values were found to be 11.56, 14.63, 17.56, 20.5 and 25.46µM.
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| Keyword:
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Aromatase; drug design; Auto Dock; Breast cancer; molecular docking; Cytotoxic activity; aromatase inhibitors.
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| EOI:
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| DOI:
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https://doi.org/10.31838/ijpr/2021.13.01.051
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| Download:
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