Manu Prince, Mensah Jehoshaphat Oppong, Gasu Edward Ntim, Borquaye Lawrence Sheringham
Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Central Laboratory, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
J Biomol Struct Dyn. 2024 Oct;42(17):8920-8936. doi: 10.1080/07391102.2023.2272750. Epub 2023 Oct 23.
is the parasite that causes the chronic malady known as Chagas disease (CD). Only nifurtimox and benznidazole are currently approved to treat CD in acute and chronic phases. To minimize the danger of disease transmission and as a therapy, new compounds that are safer and more effective are required. It has been demonstrated that plants suppress the growth of the causative agent of CD. However, little research has been done on their potential protein targets in the parasite. In this study, an approach was used to investigate the interactions of the alkaloids with trans-sialidase, a confirmed protein target of . The nature and efficiency of the main binding modes of the alkaloids were investigated by molecular docking. Trans-sialidase active site residues were bound by the alkaloids with binding energies varying from -8.9 to -6.9 kcal/mol. From the molecular docking investigation, all the alkaloids had strong interactions with the crucial amino acid residues (Glu230, Tyr342, and Asp59) required for trans-sialidase catalysis. Montanine was the most stable compound throughout the molecular dynamics simulation and had a favorable docking binding energy (-8.9 kcal/mol). The binding free energy (MM-GBSA) of the montanine complex was -14.6 kcal/mol. The pharmacokinetic properties investigated demonstrated that all the evaluated compounds exhibit suitable oral administration requirements. Overall, this study suggests that the Amaryllidaceae alkaloids could potentially act as inhibitors of trans-sialidase.Communicated by Ramaswamy H. Sarma.
是导致被称为恰加斯病（CD）的慢性疾病的寄生虫。目前仅硝呋莫司和苯硝唑被批准用于治疗急性期和慢性期的CD。为了将疾病传播的风险降至最低并作为一种治疗方法，需要更安全、更有效的新化合物。已经证明植物能抑制CD病原体的生长。然而，关于它们在寄生虫中的潜在蛋白质靶点的研究很少。在本研究中，采用一种方法来研究生物碱与转唾液酸酶（一种已确认的蛋白质靶点）的相互作用。通过分子对接研究了生物碱主要结合模式的性质和效率。生物碱与转唾液酸酶活性位点残基结合，结合能在-8.9至-6.9千卡/摩尔之间变化。从分子对接研究来看，所有生物碱都与转唾液酸酶催化所需的关键氨基酸残基（Glu230、Tyr342和Asp59）有强烈相互作用。在整个分子动力学模拟中，蒙他宁是最稳定的化合物，对接结合能良好（-8.9千卡/摩尔）。蒙他宁复合物的结合自由能（MM-GBSA）为-14.6千卡/摩尔。所研究的药代动力学性质表明，所有评估的化合物都表现出合适的口服给药要求。总体而言，这项研究表明石蒜科生物碱可能潜在地作为转唾液酸酶的抑制剂。由拉马斯瓦米·H·萨尔马传达。
