Baladhandapani Aruchamy

New 4‐nitrobenzyl derivatives were designed and synthesised by nucleophilic substitution reactions of 4‐nitrobenzyl bromide with malonic acid and its derivatives. The synthesised molecules were characterised using mass analysis and spectroscopic techniques and tested for their antioxidant properties using various methods, such as nitric oxide, DPPH, and hydrogen peroxide radical scavenging methods. The anti‐inflammatory activities of the molecules were assessed using RBC membrane stabilisation and albumin denaturation methods. We evaluated the compounds’ potential anti‐prostate cancer activity using the DU145 cell line. The MTT assay determined the cell viability, indicating good anti‐proliferative activity. The molecule 3 c exhibited the highest potency, with a CTC₅₀ of 11.83 μg/mL. Molecular dynamics simulations were performed to study the stability of the ligand within the protein after docking and the resulting protein‐ligand complex. The in vivo analysis of molecule 3 c in the DAL xenograft model demonstrated promising results. The increase in life span, reduction in tumor volume, and comparable effects to standard drugs are encouraging features that suggest that molecule 3 c may possess significant potential as an anti‐cancer agent. The research also implies that these molecules might be potential lead compounds for developing new prostate cancer drugs.

The tetra‐substituted imidazole offers more possibilities for modification and functionalization, allowing for fine‐tuning of the compound‘s biological activity. The substituents attached to the imidazole ring can be strategically chosen to introduce specific functional groups, steric effects, or electronic properties, thereby influencing the compound‘s overall bioactivity. An efficient one‐pot synthesis of 2,4,5‐tri and 1,2,4,5‐tetrasubstituted imidazoles was performed, which involves benzyl (1,2‐diphenylethane‐1,2‐dione), N ‐methyl pyrrole‐2‐carboxaldehyde, appropriate primary amine, ammonium acetate, and iodine as a catalyst. The N ‐alkylation on the imidazole was performed to introduce alkyl chains. All six synthesized compounds were purified, characterized using spectroscopic techniques, and tested against the primary Human Gingival Fibroblasts (HGFs) and AGS gastric adenocarcinoma cell line to assess their effect on cell viability. All the tested molecules displayed a low percentage of dead cells >50 μM on HGFs; compounds 1‐butyl‐2‐(1‐methyl‐1 H ‐pyrrol‐2‐yl)‐4,5‐diphenyl‐1 H ‐imidazole (5b) and 2‐(1‐methyl‐1 H ‐pyrrol‐2‐yl)‐1‐pentyl‐4,5‐diphenyl‐1 H ‐imidazole (5c) have demonstrated a remarkable ability to counteract cell viability than the other compounds, specifically on AGS cells, up to a concentration of 10 μM. This suggests that these two compounds have a higher potency in reducing the viability of AGS cells than the other tested compounds. These results align with current studies highlighting the enhanced anticancer efficacy of imidazole‐pyrrole hybrids against AGS cell line.

An overview of pyrroles as distinct scaffolds with therapeutic potential and the significance of pyrrole derivatives for drug development are provided in this article. It lists instances of naturally occurring pyrrole‐containing compounds and describes the sources of pyrroles in nature, including plants and microbes. It also explains the many conventional and modern synthetic methods used to produce pyrroles. The key topics are the biological characteristics, pharmacological behavior, and functional alterations displayed by pyrrole derivatives. It also details how pyrroles are used to treat infectious diseases. It describes infectious disorders resistant to standard treatments and discusses the function of compounds containing pyrroles in combating infectious diseases. Furthermore, the review covers the uses of pyrrole derivatives in treating non‐infectious diseases and resistance mechanisms in non‐infectious illnesses like cancer, diabetes, and Alzheimer's and Parkinson's diseases. The important discoveries and probable avenues for pyrrole research are finally summarized, along with their significance for medicinal chemists and drug development. A reference from the last two decades is included in this review.