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In silico molecular docking studies and MM/GBSA analysis of coumarin-carbonodithioate hybrid derivatives divulge the anticancer potential against breast cancer
Beni-Suef University Journal of Basic and Applied Sciences ( IF 2.5 ) Pub Date : 2020-08-17 , DOI: 10.1186/s43088-020-00059-7
Shridhar Veeresh Pattar , Shakeel Ahamed Adhoni , Chandrappa Mukappa Kamanavalli , Suresh Sadashiv Kumbar

There are many biomarkers associated with breast cancer. Higher expression of PIK3CA (Phosphoinositide 3-kinase Cα), in its upregulated form, is associated with Hr+ and Her2− breast cancer; therefore, many drugs were synthesized against this protein to treat breast cancer patients. FDA recently approved that the drug alpelisib also inhibits PI3KCα (PDB ID-5DXT) in BC patients with Hr+ and Her2−. In present study, we have exploited fourteen coumarin-carbonodithioate derivatives and alpelisib against this protein along with eighteen others which are responsible for causing BC through computational analysis. We have used Schrödinger Maestro 11.2 version for our in silico docking study, and to calculate relative binding energies of ligands, we used prime MM-GBSA module. Docking study revealed that among all fourteen compounds, 2f, 2a, 2d, and 2e showed the highest G score than the alpelisib and coumarin against PI3KCα with − 9.3, − 9.0, − 9.0 and − 9.1 kcal/mol respectively, along with individual G score of alpelisib (− 8.9) and coumarin (− 7.9). Prime MM-GBSA analysis gave the relative binding energies of alpelisib, 2f, and 2e with − 19.94864535, − 18.63076296 and − 13.07341286 kcal/mol sequentially. This study provides an insight into the coumarin-carbonodithioate derivatives that could act as inhibitors of PI3KCα like alpelisib. Further prime MM-GBSA study revealed ligand binding energies and ligands strain energies.

中文翻译:

香豆素-二硫代碳酸酯杂化衍生物的计算机分子对接研究和 MM/GBSA 分析揭示了对乳腺癌的抗癌潜力

有许多与乳腺癌相关的生物标志物。上调形式的 PIK3CA(磷酸肌醇 3-激酶 Cα)的高表达与 Hr+ 和 Her2- 乳腺癌有关;因此,针对这种蛋白质合成了许多药物来治疗乳腺癌患者。FDA 最近批准药物 alpelisib 还可抑制 Hr+ 和 Her2- BC 患者的 PI3KCα (PDB ID-5DXT)。在目前的研究中,我们利用了 14 种香豆素-二硫代碳酸酯衍生物和 alpelisib 以及其他 18 种通过计算分析导致 BC 的蛋白质。我们使用 Schrödinger Maestro 11.2 版本进行计算机对接研究,为了计算配体的相对结合能,我们使用了 Prime MM-GBSA 模块。对接研究表明,在所有 14 种化合物中,2f、2a、2d、和 2e 显示出比 alpelisib 和香豆素对 PI3KCα 的最高 G 评分,分别为 - 9.3、- 9.0、- 9.0 和 - 9.1 kcal/mol,以及 alpelisib (- 8.9) 和香豆素 (- 7.9) 的个体 G 评分。Prime MM-GBSA 分析给出了 alpelisib、2f 和 2e 的相对结合能,依次为 - 19.94864535、- 18.63076296 和 - 13.07341286 kcal/mol。这项研究提供了对香豆素-二硫代碳酸酯衍生物的深入了解,这些衍生物可以作为 PI3KCα 的抑制剂,如 alpelisib。进一步的主要 MM-GBSA 研究揭示了配体结合能和配体应变能。Prime MM-GBSA 分析给出了 alpelisib、2f 和 2e 的相对结合能,依次为 - 19.94864535、- 18.63076296 和 - 13.07341286 kcal/mol。这项研究提供了对香豆素-二硫代碳酸酯衍生物的深入了解,这些衍生物可以作为 PI3KCα 的抑制剂,如 alpelisib。进一步的主要 MM-GBSA 研究揭示了配体结合能和配体应变能。Prime MM-GBSA 分析给出了 alpelisib、2f 和 2e 的相对结合能,依次为 - 19.94864535、- 18.63076296 和 - 13.07341286 kcal/mol。这项研究提供了对香豆素-二硫代碳酸酯衍生物的深入了解,这些衍生物可以作为 PI3KCα 的抑制剂,如 alpelisib。进一步的主要 MM-GBSA 研究揭示了配体结合能和配体应变能。
更新日期:2020-08-17
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