Adokoh Christian K, Boadu Akwasi, Asiamah Isaac, Agoni Clement
Department of Forensic Sciences, School of Biological Sciences, College of Agriculture and Natural Sciences, University of Cape Coast, Cape Coast, Ghana.
Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Front Chem. 2024 Jul 25;12:1424019. doi: 10.3389/fchem.2024.1424019. eCollection 2024.
The human immunodeficiency virus (HIV) remains a significant global health concern, with a reported high infection rate of 38.4 million cases globally; an estimated 2 million new infections and approximately 700,000 HIV/AIDS-related deaths were reported in 2021. Despite the advent of anti-retroviral therapy (ART), HIV/AIDS persists as a chronic disease. To combat this, several studies focus on developing inhibitors targeting various stages of the HIV infection cycle, including HIV-1 protease. This study aims to synthesize and characterize novel glyco diphenylphosphino metal complexes with potential HIV inhibitory properties. A series of new gold(I) thiolate derivatives and three bimetallic complexes, incorporating amino phosphines and thiocarbohydrate as auxiliary ligands, were synthesized using procedures described by Jiang, et al. (2009) and Coetzee et al. (2007). Structural elucidation and purity assessment of the synthesized compounds (-) were conducted using micro-analysis, NMR, and infrared spectrometry. Using molecular modeling techniques, three of the metal complexes were identified as potential HIV protease inhibitors, exhibiting strong binding affinity interactions with binding pocket residues. These inhibitors demonstrated an ability to inhibit the flexibility of the flap regions of the HIV protease, similar to the known HIV protease inhibitor, darunavir. This study sheds light on the promising avenues for the development of novel therapeutic agents against HIV/AIDS.
人类免疫缺陷病毒(HIV)仍然是一个重大的全球健康问题,据报道全球感染率高达3840万例;2021年估计有200万新感染病例,约70万人死于与HIV/AIDS相关的疾病。尽管抗逆转录病毒疗法(ART)已经出现,但HIV/AIDS仍然是一种慢性病。为了应对这一问题,一些研究专注于开发针对HIV感染周期各个阶段的抑制剂,包括HIV-1蛋白酶。本研究旨在合成并表征具有潜在HIV抑制特性的新型糖基二苯基膦金属配合物。使用Jiang等人(2009年)和Coetzee等人(2007年)描述的方法合成了一系列新的金(I)硫醇盐衍生物和三种双金属配合物,其中氨基膦和硫代碳水化合物作为辅助配体。使用微量分析、核磁共振和红外光谱对合成化合物(-)进行结构解析和纯度评估。通过分子建模技术,确定其中三种金属配合物为潜在的HIV蛋白酶抑制剂,它们与结合口袋残基表现出强烈的结合亲和力相互作用。这些抑制剂表现出抑制HIV蛋白酶 flap区域灵活性的能力,类似于已知的HIV蛋白酶抑制剂达芦那韦。本研究为开发针对HIV/AIDS的新型治疗药物提供了有前景的途径。