A click chemistry approach for the synthesis of cyclic ureido tethered coumarinyl and 1-aza coumarinyl 1,2,3-triazoles as inhibitors of Mycobacterium tuberculosis H37Rv and their in silico studies

• Published in: Bioorganic & medicinal chemistry Vol. 27; no. 20; p. 115054
• Main Authors: Khanapurmath, Netravati, Kulkarni, Manohar V., Joshi, Shrinivas D., Anil Kumar, G.N.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-10-2019
• Subjects: 4-(Azidomethyl)-2H-chromen-2-ones/quinolin-2(1H)-ones; Click triazole; Mycobacterium tuberculosis H37Rv; Surflex-Dock algorithm; Click triazole; 4-(Azidomethyl)-2H-chromen-2-ones/quinolin-2(1H)-ones; Surflex-Dock algorithm; Mycobacterium tuberculosis H37Rv
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2019.115054

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•Cyclic ureido based mono/bis-coumarin ‘click triazoles’ have been synthesized.•Newly synthesized triazoles inhibited Mycobacterium tuberculosis H37Rv.•Benzimidazolono-bis-coumarinyl triazoles exhibited lower MIC values.•Theophylline/uracil-based mono/bis-coumarin triazoles exhibited higher MIC values.•Cytotoxicity studies exhibited IC50 values 10 times higher than Mtb MIC values.
Nucleoside bases like uracil, pharmacophoric triazoles and benzimidazolones have been used during the present study to design molecular matrices for antitubercular activity, employing Click Chemistry. Click triazoles 4/7/10 have been obtained by the reaction of 4-(Azidomethyl)-2H-chromen-2-ones/quinolin-2(1H)-ones 3 and propargyl ethers 2/6/9 derived from theophylline/6-methyl uracil/2-benzimidazolone respectively. In addition to spectral data structures have been confirmed by single crystal X-ray diffraction studies in case of uracil bis alkyne (6) and theophylline mono triazole (4c). Theophylline linked mono triazoles, 4(a-d) and 6-methyl uracil linked bis triazoles, 7(a-e) have been found to inhibit Mycobacterium tuberculosis H37Rv with MIC values in the range 55.62–115.62 μM. Benzimidazolone bis triazoles, 10(a-n) showed better activity with MIC in the range 2.33–18.34 μM. Molecular modeling studies using Surflex-Dock algorithm supported our results.