Synthesis of 2-(6-substituted quinolin-4-yl)-1-(4-aryl-1H-1,2,3-triazol-1-yl) propan-2-ol as potential antifungal and antitubercular agents

Abstract

The intense pressure of resistance to antibiotics leads the whole world's health security to drastic conditions due to Mycobacterial and fungal infections. To search for potent antifungal and antitubercular lead compounds, the synthesis of a new series of 2-(6-substituted quinolin-4-yl)-1-(4-aryl-1H-1,2,3-triazol-1-yl)propan-2-ol, (9a-l) derivatives by click reaction of 1-azido-2-(quinolin-4-yl)propan-2-ol, (7a-d) and substituted ethynylbenzene (8a-c) is reported. The structures of the novel synthesized 2-(6-substituted quinolin-4-yl)-1-(4-aryl-1H-1,2,3-triazol-1-yl)propan-2-ol derivatives were characterized by 1H NMR, 13C NMR spectroscopic and Mass spectrometric analysis. The synthesized compounds were examined for antifungal activity against C. albicans (NCIM 3100), A. niger (ATCC 504) and antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB) (ATCC 25177). Eleven derivatives showed good to excellent antifungal activity against A. niger with MIC 7.81–62.5 ​μg/mL. To study the plausible antifungal mode of action, compounds 9e, 9f, 9g, 9i, and 9k were further evaluated for the ergosterol biosynthesis inhibition activity. All these compounds showed ergosterol biosynthesis inhibition activity. All twelve derivatives of 2-(6-substituted quinolin-4-yl)-1-(4-aryl-1H-1,2,3-triazol-1-yl)propan-2-ol, (9a-l) showcased excellent antitubercular activity against M. tuberculosis H37Rv with MIC 1.6–3.2 ​μg/mL. No significant cytotoxic activity was displayed by these novel derivatives against l929 mouse fibroblast cells. The potential antifungal and antitubercular activities compelled the conclusion that the 2-(6-substituted quinolin-4-yl)-1-(4-aryl-1H-1,2,3-triazol-1-yl)propan-2-ol derivatives could assist in the development of lead compounds for the treatment of tuberculosis and fungal infections.