Synthesis, antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles

Abstract

In a search for safer and potent antitubercular agents, here a library of newly substituted dioxoisoindolinylmethyl-triazolyl-N-phenylacetamide derivatives (5a–l) has been synthesized via click chemistry approach. All synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis H₃₇Rv (MTB). Among the screened compounds, 5d, 5e, 5h, and 5l showed good antitubercular activity. The compounds 5d and 5l have shown very effective antitubercular activity against Mycobacterium tuberculosis H₃₇Rv (MTB) with MIC 12.5 μg/mL. All the newly synthesized compounds were thoroughly characterized by ¹H NMR, ¹³C NMR, and HRMS spectral data. We further performed exploratory docking studies on the crystal structure of Mycobacterium tuberculosis enoyl reductase to demonstrate the mechanism of antitubercular activity.

GRAPHICAL ABSTRACT

KEYWORDS:

• Antitubercular activity
• click chemistry
• molecular docking study
• N-phenylacetamide
• phthalimide
• 1,2,3-triazole

Acknowledgement

Authors are thankful to Professor R. A. Mane for his invaluable discussions and guidance. Authors are also very much grateful to Birla Institute of Technology and Science-Pilani, Hyderabad Campus for providing screening data of synthesized compounds.

Additional information

Funding

One of the authors, PHATAK PRAMOD SHAHAJEE has received UGC Junior Research Fellowship (JRF). The Sr. No. 2061410333 and Ref. No. 22/06/2014 (i) EU-V.