Swain Shasank S, Sahu Mahesh C, Padhy Rabindra N
Central Research Laboratory, IMS and Sum Hospital, Siksha 'O' Anusandhan University, K-8 Kalinga Nagar, Bhubaneswar 751003, Odisha, India.
Central Research Laboratory, IMS and Sum Hospital, Siksha 'O' Anusandhan University, K-8 Kalinga Nagar, Bhubaneswar 751003, Odisha, India.
Comput Methods Programs Biomed. 2015 Oct;122(1):16-25. doi: 10.1016/j.cmpb.2015.06.005. Epub 2015 Jun 25.
With the aim of controlling drug resistant Plasmodium falciparum, a computational attempt of designing novel adduct antimalarial drugs through the molecular docking method of combining chloroquine with five alkaloids, individually is presented. These alkaloids were obtained from the medicinal plant, Adhatoda vasica. From the obtained individual docking values of important derivatives of quinine and chloroquine, as well as, individual alkaloids and adduct agents of chloroquine with Adhatoda alkaloids as ligands, it was discernible that the 'adduct agent-1 with chloroquine and adhatodine' combination had the minimum energy of interaction, as the docking score value of -11.144 kcal/mol against the target protein, triosephosphate isomerase (TIM), the key enzyme of glycolytic pathway. Drug resistance of P. falciparum is due to a mutation in the polypeptide of TIM. Moratorium of mutant TIM would disrupt the metabolism during the control of the drug resistant P. falciparum. This in silico work helped to locate the 'adduct agent-1 with chloroquine and adhatodine', which could be taken up by pharmacology for further development of this compound as a new drug against drug resistant Plasmodium.
为了控制抗药性恶性疟原虫,本文介绍了一种通过将氯喹与五种生物碱分别结合的分子对接方法来设计新型加合物抗疟药物的计算尝试。这些生物碱从药用植物鸭嘴花中获得。从奎宁和氯喹的重要衍生物、以及以鸭嘴花生物碱为配体的氯喹的单个生物碱和加合物的对接值可以看出,“氯喹与鸭嘴花碱的加合物-1”组合具有最小的相互作用能,其针对目标蛋白磷酸丙糖异构酶(TIM)(糖酵解途径的关键酶)的对接得分值为-11.144千卡/摩尔。恶性疟原虫的抗药性是由于TIM多肽的突变。突变型TIM的抑制将在控制抗药性恶性疟原虫的过程中扰乱新陈代谢。这项计算机模拟工作有助于确定“氯喹与鸭嘴花碱的加合物-1”,药理学可采用该化合物进一步开发作为一种抗抗药性疟原虫的新药。