Design of chiral 2-oxazoline-based amino acid bioConjugates as anticancer agents: Synthesis, in vitro anticancer activity, ADMET prediction with molecular docking and molecular dynamic simulation insights.

This study presents the design concept of a new series of 2-oxazoline-based amino acid bioConjugates as potential anticancer agents. The designed bioConjugates (5A-F) were synthesized and characterized using 1HNMR, 13CNMR, FTIR, and Mass spectrometry. Their cytotoxic activities were investigated against the cancer cell lines of Skove3 (ovarian cancer), MCF-7 (breast cancer), and the HFF non-cancerous cell line using an MTT assay. All of the tested bioConjugates demonstrated a dose-dependent inhibitory effect. Among them, compounds B, C, and D emerged as promising candidates in the series, with IC50 values of 0.11 ± 0.01 mM, 0.26 ± 0.01 mM, and 0.22 ± 0.01 mM respectively, against the Skove3 cancer cell line. They also inhibited the growth of the MCF-7 cancer cell line with IC50 values of 0.12 ± 0.01 mM, 0.11 ± 0.02 mM, and 0.12 ± 0.05 mM, respectively. No cytotoxicity was observed on the normal cell line (HFF) at concentrations lower than 100 μM. Molecular docking and Molecular Dynamics (MD) simulation studies confirmed that compounds C and A specifically bind to the ATP-binding cleft of EGFR and VEGFR proteins respectively, possibly involved in the action mechanism, through a combination of hydrogen bonding and hydrophobic interactions. These findings can rationalize why compound C is more effective than other compounds in the series. These results suggest that the oxazoline-based amino acid bioconjugate may hold promise for developing novel chemotherapeutic agents.