<i>In vitro</i> and <i>In silico</i> Molecular Modeling Studies of Newly Synthesized Pyrrole Derivatives for their Antimicrobial and Anticancer Properties

Background: Pyrroles are biologically active scaffolds that can have a number of different effects. They also have unique pharmacophores inside their ring system that make it easier to make molecules that are more active. Significantly, in the past ten years, research has been conducted on the anti-bacterial properties, with a particular emphasis on drug-resistant Gram-positive and Gram-negative pathogens such as mycobacteria. Additionally, scaffolds based on pyrroles were utilized in the production of anti-tumor medicines that function by modulating or suppressing genes. Objective: This research aimed to create new pyrrole derivatives by chemical means and evaluate their antimicrobial and anticancer properties. Methods: By reacting diverse 1H-pyrrole-2-carbohydrazide derivatives with benzaldehyde under normal conditions, a number of pyrrole variations were created. IR, mass spectroscopy, NMR, and elemental analysis were used to characterize the synthesized compounds. The serial dilution method was used to assess antimicrobial activity, along with a molecular docking study against the enzyme α-topoisomerase II (α-Topo II), which effectively controls the topology of DNA. This enzyme is strongly expressed in rapidly dividing cells and is crucial for transcription, replication, and chromosome structure. Pyrrole and its synthetic derivatives are known to exhibit strong anticancer activity by specifically targeting α-Topo II, which has led multiple researchers to investigate α-Topo II inhibitors as potential anticancer medicines. Consequently, designing pyrroline derivatives is interesting since the succinimide portion of the joined heteroaromatic molecule can selectively engage with the ATP binding pocket via the hydrogen bond network. Newer synthesized compounds were also docked via Schrodinger 2022-4 into the active pocket of the three-dimensional crystallographic structure of the ATP site of human topoisomerase IIα (htopo IIα) (PDB ID: 1zxm). Results: Among the newly synthesized pyrrole derivatives, compounds demonstrated significant anti- microbial activity. In addition, the AutoDock Vina application was used to perform in-silico docking computations. Compounds 1a and 1h were found to have a stronger antiproliferative effect than compounds against MCF-07 breast cancer cell linen our study, ligands 1a and 1b exhibited better binding energies of -5.049 and -5.035 kcal/mol, respectively. Most of the synthesized pyrrole derivatives showed promising antiproliferative effects; however, further in vivo investigations are needed to confirm or refute these results. Conclusion: The results of this investigation show that pyrrole derivatives have the potential to be effective antimicrobial and anticancer agents. While resolving safety issues, the structural alterations carried out in this study enhanced the compounds' medicinal capabilities. To clarify the underlying mechanisms of action and enhance the pharmacological characteristics of these new pyrrole derivatives, further research is necessary.