Kashaw Sushil K, Agarwal Shivangi, Mishra Mitali, Sau Samaresh, Iyer Arun K
Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India.
Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, United States.
Curr Comput Aided Drug Des. 2019;15(1):55-66. doi: 10.2174/1573409914666181015150731.
Caspase-3 plays a leading role in apoptosis and on activation, it cleaves many protein substrates in cells and causes cell death. Since many chemotherapeutics are known to induce apoptosis in cancer cells, promotion or activation of apoptosis via targeting apoptosis regulators has been suggested as a promising strategy for anticancer drug discovery. In this paper, we studied the interaction of 1,2,4-Oxadiazoles derivatives with anticancer drug target enzymes (PDB ID 3SRC).
Molecular docking studies were performed on a series of 1,2,4-Oxadiazoles derivatives to find out molecular arrangement and spatial requirements for their binding potential for caspase-3 enzyme agonistic affinity to treat cancer. The Autodock 4.2 and GOLD 5.2 molecular modeling suites were used for the molecular docking analysis to provide information regarding important drug receptor interaction.
Both suites explained the spatial disposition of the drug with the active amino acid in the ligand binding domain of the enzyme. The amino acid asparagine 273 (ASN 273) of target has shown hydrogen bond interaction with the top ranked ligand.
半胱天冬酶 -3在细胞凋亡中起主导作用，激活后，它会切割细胞中的许多蛋白质底物并导致细胞死亡。由于已知许多化疗药物可诱导癌细胞凋亡，因此通过靶向凋亡调节因子来促进或激活凋亡已被认为是一种有前景的抗癌药物发现策略。在本文中，我们研究了1,2,4 - 恶二唑衍生物与抗癌药物靶标酶（PDB ID 3SRC）的相互作用。
对一系列1,2,4 - 恶二唑衍生物进行分子对接研究，以找出它们对半胱天冬酶 -3酶激动剂亲和力的结合潜力的分子排列和空间要求，从而治疗癌症。使用Autodock 4.2和GOLD 5.2分子建模套件进行分子对接分析，以提供有关重要药物 - 受体相互作用的信息。
这两个套件都解释了药物与酶配体结合域中活性氨基酸的空间布局。靶标的天冬酰胺273（ASN 273）氨基酸已显示与排名最高的配体存在氢键相互作用。
