Tripathi Pranav, Chaudhary Ritu, Singh Ajeet
G.B. Pant Engineering College, Ghurdauri, Pauri Garhwal, Uttarakhand, India.
Bioinformation. 2014 Aug 30;10(8):502-6. doi: 10.6026/97320630010502. eCollection 2014.
Conventionally, drugs are discovered by testing chemically synthesized compounds against a battery of in vivo biological screens. Information technology and Omic science enabled us for high throughput screening of compound libraries against biological targets and hits are then tested for efficacy in cells or animals. Chancroid, caused by Haemophilus ducreyi is a public health problem and has been recognized as a cofactor for Human Immunodeficiency Virus (HIV) transmission. It facilitates HIV transmission by providing an accessible portal entry, promoting viral shedding, and recruiting macrophages as well as CD4 cells to the skin. So, there is a requirement to develop an efficient drug to combat Chancroid that can also diminish HIV infection. In-silico screening of potential inhibitors against the target may facilitate in detection of the novel lead compounds for developing an effective chemo preventive strategy against Haemophilus ducreyi. The present study has investigated the effects of approximately 1100 natural compounds that inhibit three vital enzymes viz. Phosphoenolpyruvate phosphotransferase, Acetyl-coenzyme A carboxylase and Fructose 1, 6-bisphosphatase of Haemophilus ducreyi in reference to a commercial drug Rifabutin. Results reveal that the lead compound uses less energy to bind to target. The lead compound parillin has also been predicted as less immunogenic in comparison to Rifabutin. Further, better molecular dynamics, pharmacokinetics, pharmacodynamics and ADME-T properties establish it as an efficient chancroid preventer.
传统上，药物是通过针对一系列体内生物筛选测试化学合成化合物来发现的。信息技术和组学科学使我们能够针对生物靶点对化合物库进行高通量筛选，然后对筛选出的活性物质进行细胞或动物体内的疗效测试。由杜克嗜血杆菌引起的软下疳是一个公共卫生问题，并且已被公认为是人类免疫缺陷病毒（HIV）传播的一个辅助因素。它通过提供一个可进入的入口、促进病毒脱落以及将巨噬细胞和CD4细胞募集到皮肤来促进HIV传播。因此，需要开发一种有效的抗软下疳药物，该药物还能减少HIV感染。对针对该靶点的潜在抑制剂进行计算机模拟筛选，可能有助于发现新型先导化合物，以制定针对杜克嗜血杆菌的有效化学预防策略。本研究调查了约1100种天然化合物对杜克嗜血杆菌三种重要酶即磷酸烯醇丙酮酸磷酸转移酶、乙酰辅酶A羧化酶和果糖1,6 - 二磷酸酶的抑制作用，并与市售药物利福布汀进行了比较。结果表明，先导化合物与靶点结合所需能量较少。与利福布汀相比，先导化合物土茯苓苷的免疫原性也被预测较低。此外，更好的分子动力学、药代动力学、药效学和药物代谢动力学性质使其成为一种有效的软下疳预防药物。
