de Sá Ézio R A, Souza Janilson L, Costa Rayla K M, Barros Rômulo O, de Lima Carlos E B, Lima Francisco das C A, Ramos Ricardo M
Federal Institute of Education, Science and Technology of Piauí, IFPI, Picos, Piauí, Brazil.
Graduate Program in Chemistry, Federal University of Piauí, PPGQ/UFPI, Teresina, Piauí, Brazil.
J Biomol Struct Dyn. 2023 Apr;41(6):2555-2573. doi: 10.1080/07391102.2022.2035819. Epub 2022 Feb 8.
is a protozoan transmitted by the insect , popularly known as kissing bug. This protozoan causes the Chagas disease, a Neglected Tropical Disease. This study aimed to investigate, through DFT method and B3LYP hybrid functional, the physicochemical, pharmacokinetic, and pharmacodynamic properties of the alkaloids present in the leaves of the species (jaborandi) as a potential inhibitory activity on the protease sterol 14α-demethylase of associated with the techniques of molecular docking, molecular dynamics, MM-PBSA and ADMET predictions. The molecules of isopilosine, epiisopiloturine, epiisopilosine, and pilosine showed up the lowest binding energies by molecular docking, good human intestinal absorption, low penetration in the blood-brain barrier, antiprotozoal and anticarcinogenic activities in ADMET studies. It has been observed a better binding affinity of the sterol 14α-demethylase protease with isopilosine in molecular dynamics and MM-PBSA studies, which indicates it as a potential drug candidate for Chagas disease.Communicated by Ramaswamy H. Sarma.
是一种由昆虫传播的原生动物，俗称锥蝽。这种原生动物会引发恰加斯病，一种被忽视的热带疾病。本研究旨在通过密度泛函理论（DFT）方法和B3LYP杂化泛函，研究该物种（毛果芸香）叶片中生物碱的物理化学、药代动力学和药效学性质，作为对与分子对接、分子动力学、MM-PBSA和ADMET预测技术相关的蛋白酶固醇14α-去甲基酶的潜在抑制活性。异毛果芸香碱、表异毛果芸香次碱、表异毛果芸香碱和毛果芸香碱分子通过分子对接显示出最低的结合能，在ADMET研究中具有良好的人体肠道吸收、低血脑屏障渗透率、抗原生动物和抗癌活性。在分子动力学和MM-PBSA研究中观察到固醇14α-去甲基酶蛋白酶与异毛果芸香碱具有更好的结合亲和力，这表明它是恰加斯病的潜在候选药物。由拉马斯瓦米·H·萨尔马传达。
