In vitro and In Silico Molecular Modeling Studies of Newly Synthesized Pyrrole Derivatives for their Antimicrobial and Anticancer Properties
Authors: Bhardwaj Saurabh , Sharma Shikha , Agrawal Anurag 
Published: October 2024

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.