Chandran Kaliraj, Shane Drose Ignatious, Zochedh Azar, Sultan Asath Bahadur, Kathiresan Thandavarayan
Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu India.
Department of Physics, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu India.
In Silico Pharmacol. 2022 Aug 25;10(1):14. doi: 10.1007/s40203-022-00130-4. eCollection 2022.
is a traditional plant used in Asian and African countries for its wide nutraceutical and therapeutic effects for the treatment of various ailments. The fruit of has various biological properties such as anti-bacterial, anti-oxidant, anti-cancer. Using the molecular docking based investigation; we explored around twenty three bioactive phytochemicals in fruit against human cancer. MAPK6 (mitogen-activated protein kinase 6) was selected as target protein and these twenty three phytochemicals along with a known MAPK6 inhibitor were docked against the target protein. The docking scores of the bioactive phytochemicals against MAPK6 protein range between - 4.5 kcal/mol to - 7.9 kcal/mol and the docking score of the standard drug (CID: 447077) was - 7.3 kcal/mol. Based on the binding affinity five phytochemicals asperuloside (- 6.7 kcal/mol), asperulosidic acid (- 7.2 kcal/mol), deacetylasperulosidic acid (- 7.0 kcal/mol), eugenol (- 6.8 kcal/mol) and rutin (- 7.9 kcal/mol) were chosen for further evaluation. These five compounds were further investigated through RC plot analysis, density function theory and ADMET properties. Stable linkage of protein-ligand interaction was observed through RC plot, density function theory showed the structural stability and reactivity of bioactive compounds through the energy gap between HOMO and LUMO and the ADMET (adsorption, distribution, metabolism, excretion and toxicity) studies showed the safety profile of the bioactive compounds. These in silico results support the utilization of fruit in the traditional medication and the initiation for the development of new drug against human cancer through in vivo and in vitro evaluation.
The online version contains supplementary material available at 10.1007/s40203-022-00130-4.
是一种在亚洲和非洲国家使用的传统植物，因其具有广泛的营养保健和治疗作用，可用于治疗各种疾病。其果实具有多种生物学特性，如抗菌、抗氧化、抗癌等。通过基于分子对接的研究；我们在其果实中探索了约二十三种针对人类癌症的生物活性植物化学物质。选择丝裂原活化蛋白激酶6（MAPK6）作为靶蛋白，并将这二十三种植物化学物质与一种已知的MAPK6抑制剂与靶蛋白进行对接。生物活性植物化学物质与MAPK6蛋白的对接分数在-4.5千卡/摩尔至-7.9千卡/摩尔之间，标准药物（CID：447077）的对接分数为-7.3千卡/摩尔。基于结合亲和力，选择了五种植物化学物质：车叶草苷（-6.7千卡/摩尔）、车叶草苷酸（-7.2千卡/摩尔）、去乙酰车叶草苷酸（-7.0千卡/摩尔）、丁香酚（-6.8千卡/摩尔）和芦丁（-7.9千卡/摩尔）进行进一步评估。通过RC图分析、密度泛函理论和ADMET性质对这五种化合物进行了进一步研究。通过RC图观察到蛋白质-配体相互作用的稳定联系，密度泛函理论通过最高占据分子轨道（HOMO）和最低未占据分子轨道（LUMO）之间的能隙显示了生物活性化合物的结构稳定性和反应性，ADMET（吸收、分布、代谢、排泄和毒性）研究显示了生物活性化合物的安全性。这些计算机模拟结果支持了其果实在传统药物中的应用，并为通过体内和体外评估开发抗人类癌症的新药提供了依据。
在线版本包含可在10.1007/s40203-022-00130-4获取的补充材料。
