Amino-and morpholino-chalcones: Potential anticancer agents on colorectal cancer cell lines
TL;DR
Due to their pronounced differential cytotoxicity and lowest IC50, chalcones possessing groups with a negative inductive effect in the meta position of the second ring represent the most promising leads for subsequent studies of their mechanism of action and the development of novel chemotherapeutic agents for colorectal cancer.
Abstract
Driven by the high incidence of colorectal cancer (CRC) globally, current research is focused on a multitarget strategy to inhibit inflammatory pathways and malignant cell proliferation simultaneously. In this context, elevated expression of the COX-2 enzyme plays a critical role in tumor progression. Chalcones (1,3-diaryl-2-propen-1-ones) stand out as highly promising scaffolds due to their diverse biological activities; by inhibiting COX-2, these compounds operate through a dual-action mechanism that effectively suppresses inflammatory pathways while exerting a direct cytotoxic effect on cancer cells. This study aimed to evaluate the in vitro anticancer effect of 16 structurally diverse aminoand morpholino-chalcones with various substituents on the second aromatic ring. Cytotoxicity was assessed using four CRC cell lines (HCT116, HT29, SW480, and MC38) and one healthy cell line (MRC-5). Following 72-hour incubation, cell viability was measured using MTT and crystal violet (CV) assays to determine IC50 values. All derivatives demonstrated dose-dependent cytotoxicity, and the SW480 line exhibited the highest sensitivity. Significantly higher IC50 values in non-malignant MRC-5 cells confirmed favourable tumor selectivity for all compounds. The most potent derivatives were chalcones possessing groups with a negative inductive effect in the meta position of the second ring: aminochalcone labelled as 23 (m-F) and morpholinochalcone 51 (m-CN). Due to their pronounced differential cytotoxicity and lowest IC50, these derivatives represent the most promising leads for subsequent studies of their mechanism of action and the development of novel chemotherapeutic agents for colorectal cancer.