RESUMO
The human immunodeficiency virus type 1 (HIV-1) is the major etiological agent responsible for the acquired immunodeficiency syndrome (AIDS), which is a serious infectious disease and remains one of the most prevalent problems at present. Currently, combined antiretroviral therapy is the primary modality for the treatment and management of HIV/AIDS, but the long-term use can result in major drawbacks such as the development of multidrug-resistant viruses and multiple side effects. 1,2,3-Triazole is the common framework in the development of new drugs, and its derivatives have the potential to inhibit various HIV-1 enzymes such as reverse transcriptase, integrase, and protease, consequently possessing a potential anti-HIV-1 activity. This review covers the recent advances regarding the 1,2,3-triazole hybrids with potential anti-HIV-1 activity; it focuses on the chemical structures, structure-activity relationship, and mechanisms of action, covering articles published from 2010 to 2020.
Assuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/tratamento farmacológico , Triazóis/farmacologia , Fármacos Anti-HIV/química , Humanos , Relação Estrutura-Atividade , Triazóis/químicaRESUMO
Novel clarithromycin derivatives with C-4â³ elongated arylalkyl groups were designed, synthesized and evaluated to probe the effect of different lengths of their C-4â³ side chains on the activity against resistant bacterial strains. These derivatives had excellent activity against erythromycin-susceptible Streptococcus pneumoniae, Streptococcus aureus or Streptococcus pyogenes and some of them exhibited greatly improved activity against erythromycin-resistant strains. Compounds 18 and 16, which had the C-4â³ elongated arylalkyl groups with eight atoms from the 4â³-oxygen atom to the terminal benzene ring, were the most effective against S. pneumoniae expressing the erm gene and the erm and mef genes. In contrast, the most potent compounds 3, 5, 9, 17 and 18 against S. pneumoniae expressing the mef gene had C-4â³ elongated arylalkyl groups with three to eight atoms between the 4â³-oxygen atom and the terminal aromatic ring.
Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Claritromicina/síntese química , Claritromicina/química , Desenho de Fármacos , Farmacorresistência Bacteriana , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Conformação Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A series of new 4'',11-di-O-arylalkylcarbamoyl azithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. Some derivatives exhibited greatly improved activity against erythromycin-resistant bacteria. Among them, compounds 5f and 5k were found to have potent activity against erythromycin-resistant Streptococcus pneumoniae whose resistance was encoded by the erm or mef gene.
