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

Authors

  • Claudia R. B. Gomes,

    1. Instituto de Tecnologia em Fármacos – Farmanguinhos, FioCruz – Fundação Oswaldo Cruz, R. Sizenando Nabuco, 100 Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil
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  • Marcele Moreth,

    1. Instituto de Tecnologia em Fármacos – Farmanguinhos, FioCruz – Fundação Oswaldo Cruz, R. Sizenando Nabuco, 100 Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil
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  • Danielle Cardinot,

    1. Instituto de Tecnologia em Fármacos – Farmanguinhos, FioCruz – Fundação Oswaldo Cruz, R. Sizenando Nabuco, 100 Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil
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  • Valquiria Kopke,

    1. Instituto de Tecnologia em Fármacos – Farmanguinhos, FioCruz – Fundação Oswaldo Cruz, R. Sizenando Nabuco, 100 Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil
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  • Wilson Cunico,

    1. Instituto de Tecnologia em Fármacos – Farmanguinhos, FioCruz – Fundação Oswaldo Cruz, R. Sizenando Nabuco, 100 Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil
    2. Centro de Ciências Químicas Farmacêuticas e de Alimentos, UFPel, Campus Universitário s/no, 96010-900 Pelotas, RS, Brazil
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  • Maria Cristina da Silva Lourenço,

    1. Instituto de Pesquisas Clínicas Evandro Chagas, Departamento de Bacteriologia, FioCruz – Fundação Oswaldo Cruz, Av. Brasil, 4365 Manguinhos, Rio de Janeiro, Brazil
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  • Marcus V. N. de Souza

    Corresponding author
    1. Instituto de Tecnologia em Fármacos – Farmanguinhos, FioCruz – Fundação Oswaldo Cruz, R. Sizenando Nabuco, 100 Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil
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Corresponding author: Marcus V. N. de Souza, marcos_souza@far.fiocruz.br

Abstract

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.

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