Synthesis, X-ray, antioxidant, in-vitro biological & in-silico docking studies of novel organoselenides: Promising colorectal cancer inhibitors

Abstract

A series of multi-target organoselenides 3a-h has been synthesized with the advantages of a simple operation, and good yields of 66-89 % escorted by mechanistic enlightenment. The compounds 3b, 3c continued to exist as orthorhombic and trigonal, whereas 3d exist as monoclinic confirmed by the X-ray crystallography. Organoselenides 3c and 3f displayed the highest % radical scavenging potential with % inhibition of 98.16 ± 2.1 and 97.63 ± 2.1 respectively utilizing the DPPH assay. Moreover, compounds 3c and 3f unveiled potent antibacterial activity against Gram-positive and Gram-negative bacterial strains, with notable MIC values of 8 μg/mL and 10 μg/mL against S. aureus, comparable to the standard drug Tetracycline (MIC = 8 μg/mL). Additionally, 3c and 3f demonstrated promising anticancer profiles against HCT-116 colorectal carcinoma cell lines, with IC₅₀ values of 14.77 ± 1.29 μM and 20.3 ± 0.66 μM as compared to 5-Fluorouracil (5.25 ± 0.43 μM). Furthermore, in-silico macromolecular (PDB code: 2W9S and 3RUK) interactions arrayed incremental support for the observed in-vitro antibacterial and anticancer activities of compounds 3c & 3f and subsequently unveiled these as promising colorectal cancer inhibitors with elevated D scores of -5.78 & -5.72 kcal/mol respectively. Additionally, against the antibacterial target Staphylococcus aureus dihydrofolate reductase (PDB: 2W9S), docking scores of -5.28 and -4.88 kcal/mol were observed for 3c and 3f, respectively.

Keywords: Antibacterial; Antioxidants; Colorectal cancer inhibitors; Macromolecules; Organoselenides.