Synthesis and Antimycobacterial Activity of Novel Amino Alcohols Containing Central Core of the Anti-HIV Drugs Lopinavir and Ritonavir

• Published in: Chemical biology & drug design 2011-12, Vol.78 (6), p.1031-1034
• Main Authors: Gomes, Claudia R. B., Moreth, Marcele, Cardinot, Danielle, Kopke, Valquiria, Cunico, Wilson, da Silva Lourenço, Maria Cristina, de Souza, Marcus V. N.
• Format: Article
• Language: English
• Subjects: amino alcohol; Amino Alcohols - chemical synthesis; Amino Alcohols - chemistry; Anti-HIV Agents - chemistry; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; drugs; Ethambutol - pharmacology; Human immunodeficiency virus; lopinavir; Lopinavir - chemistry; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; ritonavir; Ritonavir - chemistry; Structure-Activity Relationship; tuberculosis
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/j.1747-0285.2011.01244.x

Eleven new amino alcohol derivatives have been synthesized from reactions of lopinavir intermediate and heteroaromatic aldehyde in good yields. These compounds, the antiretrovirals (lopinavir and ritonavir) and lopinavir key intermediate were evaluated as antibacterial agents against Mycobacterium tuberculosis H37Rv using the Alamar Blue susceptibility test and their activity expressed as the minimum inhibitory concentration (MIC) in μm. Ten amino alcohols evaluated displayed significant activity (MIC between 6.15 and 108.4 μm) when compared to first‐line drug ethambutol (MIC = 15.9 μm). Three of them showed more activity than ethambutol (MIC = 6.15; 6.21 and 13.4 μm). The appreciable activity of these compounds can be considered an important finding for the rational design of new leads for anti‐TB compounds. Three of the synthesized compounds showed more anti‐TB activity than ethambutol.