Synthesis, antimicrobial activity and in-silico docking of two macrocycles based on pyrazole-tetrazole subunit

The design of two new macrocycles bearing two pyrazole-tetrazole subunits and a lateral arm is presented. These macrocycles and the intermediate compounds are characterized by NMR, FT-IR and UV-Vis spectroscopies as well as elemental analysis and mass spectrometry. Two routes were evaluated to reach this kind of structures in terms of feasibility and reaction yield. The first one was unable to achieve the desired structures and several issues were confronted. However, the second route allows the obtaining of these macrocycles in moderate yields. Their quantum parameters were also determined using DFT calculations. The antimicrobial activity of these macrocycles was evaluated and the obtained results show, that both macrocycles possess good potency to inhibit Staphylococcus aureus. In-silico docking calculations were performed on the biotin protein ligase in Staphylococcus aureus and results suggest a good interactions of macrocycles with the key residues of the active pocket.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

The design of two new macrocycles containing pyrazole-tetrazole subunits and a lateral arm is presented in this study. The synthesis and characterization of these macrocycles and intermediate compounds were conducted using various spectroscopic and analytical techniques. Two synthetic routes were evaluated, and the second route was found to be more successful in yielding the desired macrocycles. The antimicrobial activity of these macrocycles was evaluated, and in-silico docking calculations provided insights into their interaction with the target protein.