Tailoring selective triclosan azo-adducts: Design, synthesis, and anti-mycobacterial evaluation
Shekhar,
Matthéo Alcaraz,
Pule Seboletswe,
Neha Manhas,
Laurent Kremer,
Parvesh Singh,
Vipan Kumar
Affiliations
Shekhar
Department of Chemistry, Guru Nanak Dev University, Amritsar, India
Matthéo Alcaraz
Centre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, 1919 route de Mende, 34293, Montpellier, France
Pule Seboletswe
School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban, South Africa
Neha Manhas
School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban, South Africa
Laurent Kremer
Centre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, 1919 route de Mende, 34293, Montpellier, France; INSERM, IRIM, 34293 Montpellier, France
Parvesh Singh
School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban, South Africa
Vipan Kumar
Department of Chemistry, Guru Nanak Dev University, Amritsar, India; Corresponding author.
A series of triclosan azo-adducts were synthesized to investigate their structure-activity relationship against Mycobacterium tuberculosis and non-tuberculous mycobacteria. The series' most potent compound was four and sixteen times more active than triclosan and rifabutin against drug-resistant Mycobacterium abscessus, respectively, while being less cytotoxic to human macrophages than triclosan on day one. Additionally, one of the azo-adducts was twice as efficient against M. tuberculosis as triclosan and twice as effective against Mycobacterium marinum as isoniazid. Furthermore, the synthesized azo-adducts were equally effective against M. abscessus strains overexpressing InhA, suggesting that these compounds work through a distinct mechanism.
