Thipparapu Ganapathi, Ajumeera Rajanna, Venkatesan Vijayalakshmi
Stem Cell Research Division, Department of Biochemistry, National Institute of Nutrition (NIN), Indian Council of Medical Research (ICMR), Hyderabad, Telangana 500007 India.
In Silico Pharmacol. 2017 Oct 12;5:10. doi: 10.1007/s40203-017-0030-4. eCollection 2017.
Dihydropyrimidine derivatives possess many biological activities due to presence of pyrimidine ring structure in various nucleic acids, vitamins, coenzymes, uric acid and their derivatives. They have possessed broad spectrum actions like antibacterial, antifungal, antiviral, anticancer and antihypertensive etc. Before synthesis of compounds, it is good to predict biological activity using in silico methods. Here, we have selected some of N (-) and O (-) mannich bases of dihydro pyrimidine derivatives emphasized on histone deacetylase 4 (HDAC-4) inhibitions activity. We have used the different software tools like Lipinski's rule of five; pass online; osiris property explorer and docking studies to predict anti cancer activity. All the selected compounds exhibited potential drug like molecule with anti cancer activity. Among all compound the substitution with methoxy group ( exhibited more drugs like property and substation with hydrogens ( showed high anti neoplastic activity; whereas substitution with dichloro groups ( showed more drug docking scores. These were compared with standard drugs tamoxifen and 5-flourouracil. The approach of predicting anticancer activity using in silico method may be more useful to select and synthesis novel compounds in research as well as in industry.
二氢嘧啶衍生物由于在各种核酸、维生素、辅酶、尿酸及其衍生物中存在嘧啶环结构而具有许多生物活性。它们具有广谱作用，如抗菌、抗真菌、抗病毒、抗癌和抗高血压等。在化合物合成之前，使用计算机模拟方法预测生物活性是很好的。在这里，我们选择了一些二氢嘧啶衍生物的N（-）和O（-）曼尼希碱，重点研究组蛋白去乙酰化酶4（HDAC-4）抑制活性。我们使用了不同的软件工具，如Lipinski的五规则、在线通行证、奥西里斯性质探索器和对接研究来预测抗癌活性。所有选定的化合物都表现出具有抗癌活性的潜在药物样分子。在所有化合物中，用甲氧基取代（表现出更多的药物样性质），用氢取代（显示出高抗肿瘤活性）；而用二氯取代（显示出更高的药物对接分数）。将这些与标准药物他莫昔芬和5-氟尿嘧啶进行了比较。使用计算机模拟方法预测抗癌活性的方法可能对研究和工业中选择和合成新型化合物更有用。
