A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens

Author:

Leite Debora Inacio1,de Castro Bazan Moura Stefany12,da Conceição Avelino Dias Maria1ORCID,Costa Carolina Catta Preta1,Machado Gustavo Peixoto1,Pimentel Luiz Claudio Ferreira1ORCID,Branco Frederico Silva Castelo1,Moreira Rui3ORCID,Bastos Monica Macedo1,Boechat Nubia1

Affiliation:

1. 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

2. 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

3. Departamento de Química Medicinal, Faculdade de Farmácia, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal

Abstract

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 Mycobacterium tuberculosis (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.

Funder

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil

National Council of R&D of Brazil

National Council for Scientific and Technological Development—CNPq

PROEP-CNPq

Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro—FAPERJ

Programe Inova-Fiocruz

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

Reference117 articles.

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