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Design, Synthesis and Molecular docking of Phenyl [3-(1, 3-oxazol-5-yl) phenyl] carbamate derivatives as novel class of Aromatase Inhibitors in Treatment of Breast Cancer
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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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Breast cancer is one of the most common types of cancer in females. Therefore, development of potent Aromatase inhibitors (AIs) becomes important which are clinically active against estrogen production in post-menopausal women and thereby on breast cancer. Oxazole analogues can be used as non steroidal aromatase inhibitors for breast cancer therapy. Totally twenty four compounds were synthesized and evaluated for their aromatase inhibitory activity and selected derivatives were tested against breast cancer cell lines (MCF-7) to evaluate their cytotoxic effect. All the novel Phenyl[3-(1,3-oxazol-5-yl)phenyl]carbamate derivatives were docked by Auto Dock software and after screening the compounds were synthesized and characterized by FTIR, mass and NMR spectroscopy. The docking parameters revealed that polar (T310, L477, V369 and V370) and non-polar (A306, A307, M303, F430, V370 and L152) residues of aromatase were essential for interacting with the newly synthesized aromatase inhibitors. Aromatase inhibition activity of the synthesized compounds were calculated in comparison with vehicle-treated control Letrozole (IC50 16.7µM). OXA-19 showed excellent inhibition having 50% inhibitory concentration IC50 value 15.6µM. In-vitro cytotoxic activity of ten selected derivatives was performed against MCF7 cancer cell lines taking Cisplatin as reference and compounds OXA-6, OXA-11, OXA-12, OXA-18, OXA-19 and OXA-22 exhibited potent cytotoxic activity and their IC50 values were found to be 21.13, 19.3, 15.56, 16.76, 11.8 and 13.7µM respectively. Therefore to discover novel aromatase inhibitors and to find a potent anti-breast cancer drug, we have designed and synthesized a novel series of oxazole derivatives.
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| Keyword:
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Drug design; Auto Dock; Breast cancer; cytotoxic activity; docking; Non-steroidal aromatase inhibitor; aromatase inhibition assay.
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| EOI:
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-
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| DOI:
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https://doi.org/10.31838/ijpr/2020.SP1.286
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| Download:
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