Laboratorio de Sintese de Farmacos (LASFAR), Fundacao Oswaldo Cruz, Instituto de Tecnologia em Farmacos (Farmanguinhos), Fiocruz, Rua Sizenando Nabuco, 100 Manguinhos, Rio de Janeiro 21041-000, Brazil.
Programa de Pos-Graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas (ICB), Universidade Federal do Rio de Janeiro (UFRJ), Av. Carlos Chagas Filho, Rio de Janeiro 21941-902, Brazil.
Molecules. 2023 Apr 10;28(8):3342. doi: 10.3390/molecules28083342.
The human immunodeficiency virus (HIV) produces the pathologic basis of acquired immunodeficiency syndrome (AIDS). An increase in the viral load in the body leads to a decline in the number of T lymphocytes, compromising the patient's immune system. Some opportunistic diseases may result, such as tuberculosis (TB), which is the most common in seropositive patients. Long-term treatment is required for HIV-TB coinfection, and cocktails of drugs for both diseases are used concomitantly. The most challenging aspects of treatment are the occurrence of drug interactions, overlapping toxicity, no adherence to treatment and cases of resistance. Recent approaches have involved using molecules that can act synergistically on two or more distinct targets. The development of multitarget molecules could overcome the disadvantages of the therapies used to treat HIV-TB coinfection. This report is the first review on using molecules with activities against HIV and (MTB) for molecular hybridization and multitarget strategies. Here, we discuss the importance and development of multiple targets as a means of improving adherence to therapy in cases of the coexistence of these pathologies. In this context, several studies on the development of structural entities to treat HIV-TB simultaneously are discussed.
人类免疫缺陷病毒 (HIV) 产生获得性免疫缺陷综合征 (AIDS) 的病理基础。体内病毒载量的增加导致 T 淋巴细胞数量减少,从而损害患者的免疫系统。可能会发生一些机会性疾病,如结核病 (TB),这在血清阳性患者中最为常见。HIV-TB 合并感染需要长期治疗,并且同时使用两种疾病的药物鸡尾酒。治疗中最具挑战性的方面是药物相互作用的发生、重叠毒性、不遵医嘱和耐药性病例。最近的方法涉及使用可以协同作用于两个或多个不同靶点的分子。开发多靶分子可以克服用于治疗 HIV-TB 合并感染的疗法的缺点。本报告是第一篇关于使用针对 HIV 和结核分枝杆菌 (MTB) 的活性分子进行分子杂交和多靶点策略的综述。在这里,我们讨论了作为提高这些病理共存时治疗依从性的一种手段的多个靶点的重要性和发展。在这方面,讨论了针对同时治疗 HIV-TB 的结构实体的开发的几项研究。