Insights into Novel Tetrazole-Encompassing 1,2,3-Triazoles as Antimicrobial and Anti-TB Agents: Synthesis, ADME-Tox, and In Silico Molecular Docking

Objective: The 1,2,3-triazole nucleus exhibits various biological activities and is an integral part of many naturally occurring and synthetic heterocyclic derivatives. This study aims to synthesise and evaluate the antimicrobial and anti-TB efficacy of a series of 1,2,3-triazole-linked tetrazole derivatives as potential therapeutic agents against antibiotic-resistant bacteria and TB. Methods: A new kind of 1,2,3-triazolyl-tetrazoles bearing cycloheptapyridinone conjugates was synthesised using click chemistry. HRMS spectrometry, FT-IR, and NMR (1H and 13C) were all utilised to characterise each of the recently generated scaffolds. The antimicrobial and antitubercular activities of the newly synthesised hybrids were assessed by minimum inhibitory concentration (MIC) measurements, and computational studies were conducted using AutoDock Tools. Results and Discussion: All synthesised compounds possess an active 1,2,3-triazole moiety in their structure, and the cycloheptapyridinone nucleus has a hydroxy group at the 9th position. According to the results obtained, tetrazole compounds VIIId, VIIIh, and VIIIi were particularly effective at inhibiting the growth of all tested bacteria, with MIC values ranging from 0.983 to 16.762 μg/mL; compared to moxifloxacin (MXF) (2.191 to 10.01 μg/mL). The highest antitubercular properties were shown by compounds VIIId and VIIIi, with MIC values of 2.20 and 2.10 μg/mL against the H37Rv strain. Furthermore, compounds VIIIb, VIIIh, and VIIIi demonstrated better binding energies and inhibition constants for K. pneumoniae and Mycobacterium tuberculosis (PDB ID: 6JYY and 1DF7). Conclusions: The synthesised cycloheptapyridinone compounds present a promising basis for the development of biosafe and pharmacologically active scaffolds for novel therapeutics.