Synthesis and In-silico Docking Analysis of 2-Phenylindolizine Acetamide Scaffolds: Potent Anticancer and Antibacterial Ta

Abstract

Background: Although several specialized methods for treating various cancers have been developed, clinical outcomes for patients with colon cancer have shown unfavorable effects in addition to chemotherapeutic drug resistance. Therefore, finding medicinal substances with minimal to no side effects is crucial in the fight against cancer. Further, this study underscores the significance of 2-phenylindolizine acetamide due to the diverse biological features and the extensive application of this moiety as an effective anticancer and antibacterial drug. Objective: The goal of the study was to investigate novel, prospective 2-phenylindolizines as anticancer and antibacterial drugs. Methods: The synthesized compounds were characterized by different spectral analyses like 1 H NMR, 13C NMR, IR, and mass spectrometry. Pharmacokinetics in-silico studies were performed to predict the drug performance in the body using the SwissADME kit. The molecular docking was performed to check the catalytic binding site between the Topoisomerase-IV from S. pneumoniae and synthesized compounds. The antibacterial activity was assessed using the agar well diffusion method, and the compounds were screened for in vitro anticancer activity using an MTT assay with doxorubicin as a reference. Results: Interestingly, 2-phenylindolizine scaffolds 7c, 7f, and 7g revealed a remarkable antibacterial activity against relevant organisms S. aureus, E. coli, S. pneumoniae, and P. aeruginosa. The target compounds 7e and 7h showed excellent anticancer activity against Colo-205 and MDA-MB-231 cell lines with IC50 values of 68.62, 62.91, 54.23, and 46.34 µM, respectively. Compounds 7a, 7f, and 7c exhibited the highest hydrogen bonding amino acid interactions Asp83 (2.23 Å), Asp83 (2.08 Å), His74 (2.05 Å), His76 (1.71 Å), and Ser80 (1.05 Å) with active site of Topoisomerase-IV from S. pneumoniae (4KPE). Conclusion: This research focused on recent advances in drug design and development, as well as Phenylindolizine derivatives and how they work on anticancer and antibacterial sites of action.