Synthesis, antimicrobial and cytotoxic activities of tetrazole N-Mannich base derivatives: Investigation of DFT calculation, molecular docking, and Swiss ADME studies

Abstract

Tetrazole derivatives are a prime class of heterocyclic compounds that are important for the design of drug molecules. In this study, the cytotoxicity and antimicrobial activity of a novel class of tetrazole N-Mannich base derivatives were investigated. The synthesised compounds were evaluated by FTIR, NMR spectroscopy, mass spectrometry, and elemental analysis. All synthesised compounds were investigated for antimicrobial activity; in particular, compound 2d was found to be more effective against S. aureus than cefazolin. Compound 2e was more effective than clotrimazole against Cryptococcus neoformans. All the synthesised compounds were investigated against cancer cell lines (HepG2, MCF-7, and HeLa); in particular, compound 2e was more active against the HeLa cancer cell line than doxorubicin. Synthesised compounds were studied for molecular docking interactions between proteins and synthesised molecules using the Auto Dock Vina 1.1.2 programme. According to molecular docking studies, 2d has a greater docking score (-6.4 kcal/mol) compared with cefazolin (-5.8 kcal/mol) for the 1BQB protein and 2e was equal docking score compared with clotrimazole (-2.3 kcal/mol) for the 3SFX protein. Density functional theory (DFT) was used to perform calculations for highly and low-active compounds in order to estimate the energy gaps 2e and 2d (∆E = 0.1, and 0.21 eV). Additionally, we discuss the role of the Swiss ADME tool in determining the physicochemical properties of all synthesised compounds. According to the results, the newly synthesised tetrazole derivatives may have medicinal importance and could be used as antibacterial agents.