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In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies of substituted 1,2,4-oxadiazole analogues against Mycobacterium tuberculosis.
Deb, Pran Kishore; Al-Shar'i, Nizar A; Venugopala, Katharigatta N; Pillay, Melendhran; Borah, Pobitra.
Afiliação
  • Deb PK; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, Amman, Jordan.
  • Al-Shar'i NA; Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
  • Venugopala KN; Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Kingdom of Saudi Arabia.
  • Pillay M; Department of Biotechnology and Food Technology, Durban University of Technology, Durban, South Africa.
  • Borah P; Department of Microbiology, National Health Laboratory Services, KZN Academic Complex, Inkosi Albert Luthuli Central Hospital, Durban, South Africa.
J Enzyme Inhib Med Chem ; 36(1): 869-884, 2021 Dec.
Article em En | MEDLINE | ID: mdl-34060396
The alarming increase in multi- and extensively drug-resistant (MDR and XDR) strains of Mycobacterium tuberculosis (MTB) has triggered the scientific community to search for novel, effective, and safer therapeutics. To this end, a series of 3,5-disubstituted-1,2,4-oxadiazole derivatives (3a-3i) were tested against H37Rv, MDR and XDR strains of MTB. Of which, compound 3a with para-trifluorophenyl substituted oxadiazole showed excellent activity against the susceptible H37Rv and MDR-MTB strain with a MIC values of 8 and 16 µg/ml, respectively.To understand the mechanism of action of these compounds (3a-3i) and identify their putative drug target, molecular docking and dynamics studies were employed against a panel of 20 mycobacterial enzymes reported to be essential for mycobacterial growth and survival. These computational studies revealed polyketide synthase (Pks13) enzyme as the putative target. Moreover, in silico ADMET predictions showed satisfactory properties for these compounds, collectively, making them, particularly compound 3a, promising leads worthy of further optimisation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxidiazóis / Mycobacterium tuberculosis / Antituberculosos Tipo de estudo: Prognostic_studies Idioma: En Revista: J Enzyme Inhib Med Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Jordânia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxidiazóis / Mycobacterium tuberculosis / Antituberculosos Tipo de estudo: Prognostic_studies Idioma: En Revista: J Enzyme Inhib Med Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Jordânia