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Exploring rhodanine linked enamine-carbohydrazide derivatives as mycobacterial carbonic anhydrase inhibitors: Design, synthesis, biological evaluation, and molecular docking studies.
Maddipatla, Sarvan; Bakchi, Bulti; Gadhave, Rutuja Rama; Ammara, Andrea; Sau, Shashikanta; Rani, Bandela; Nanduri, Srinivas; Kalia, Nitin Pal; Supuran, Claudiu T; Yaddanapudi, Venkata Madhavi.
Afiliação
  • Maddipatla S; Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
  • Bakchi B; Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
  • Gadhave RR; Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
  • Ammara A; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Sesto Fiorentino, Firenze, Italy.
  • Sau S; Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
  • Rani B; Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
  • Nanduri S; Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
  • Kalia NP; Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
  • Supuran CT; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Sesto Fiorentino, Firenze, Italy.
  • Yaddanapudi VM; Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
Arch Pharm (Weinheim) ; 357(7): e2400064, 2024 Jul.
Article em En | MEDLINE | ID: mdl-38498883
ABSTRACT
With the rise of multidrug-resistant tuberculosis, the imperative for an alternative and superior treatment regimen, incorporating novel mechanisms of action, has become crucial. In pursuit of this goal, we have developed and synthesized a new series of rhodanine-linked enamine-carbohydrazide derivatives, exploring their potential as inhibitors of mycobacterial carbonic anhydrase. The findings reveal their efficacy, displaying notable selectivity toward the mycobacterial carbonic anhydrase 2 (mtCA 2) enzyme. While exhibiting moderate activity against human carbonic anhydrase isoforms, this series demonstrates promising selectivity, positioning these compounds as potential antitubercular agents. Compound 6d was the best one from the series with a Ki value of 9.5 µM toward mtCA 2. Most of the compounds displayed moderate to good inhibition against the Mtb H37Rv strain; compound 11k showed a minimum inhibitory concentration of 1 µg/mL. Molecular docking studies revealed that compounds 6d and 11k show metal coordination with the zinc ion, like classical CA inhibitors.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rodanina / Inibidores da Anidrase Carbônica / Desenho de Fármacos / Testes de Sensibilidade Microbiana / Simulação de Acoplamento Molecular / Hidrazinas / Mycobacterium tuberculosis / Antituberculosos Limite: Humans Idioma: En Revista: Arch Pharm (Weinheim) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Índia País de publicação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rodanina / Inibidores da Anidrase Carbônica / Desenho de Fármacos / Testes de Sensibilidade Microbiana / Simulação de Acoplamento Molecular / Hidrazinas / Mycobacterium tuberculosis / Antituberculosos Limite: Humans Idioma: En Revista: Arch Pharm (Weinheim) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Índia País de publicação: Alemanha