1.Synthesis, characterization, anti-mycobacterial activity and in silico study of new 2,5-disubstituted-1,3,4-oxadiazole derivatives
Azmi, M.N. ; Hasmaruddin, N.S. ; Mat Ali, N.A. ; Osman, H. ; Mohamad, S. ; Parumasivam, T. ; Hassan, M.Z. ; Abd Ghani, M.S. ; Awang, K.
Tropical Biomedicine 2022;39(No.3):467-475
A series of new 2,5-disubstituted-1,3,4-oxadiazole derivatives (5a-j and 6a-j) have been designed and
synthesized in four-steps. Sixteen compounds among the twenty compounds are reported for the first
time. The compounds were characterized and confirmed by the FTIR, 1D- and 2D-NMR and HRMS
analyses, and were tested against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Ra.
Compound 5d was the most active against M. smegmatis with MIC value of 25 µM, and exhibited
cidal activity with MBC of 68 µM, respectively. The time-kill assay showed the good killing rate at 77%
with the combination of isoniazid (INH). In addition, checkboard assay confirmed the interaction of
compound 5d was categorised as additive. Docking simulation has been performed to position 5d into
the pantothenate synthetase active site with binding free energy value –8.6 kcal mol-1. It also occupied
the same active site as that of standard native ligand with similar interactions, which clearly indicate
their potential as pantothenate synthetase inhibitor.
Result Analysis
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