Synthesis and characterization of 7-diethylamino-4-Chloromethyl coumarin: Spectroscopic analysis, molecular docking, and anticancer activity on large intestine carcinoma cells

Cancer, characterized by uncontrolled cell growth and metastasis, poses a significant global health burden, ranking as a leading cause of mortality worldwide. Colorectal cancer (CRC) specifically accounts for a substantial portion of cancer cases, with increasing incidence projected over the coming decades. While conventional treatments exist, they often entail adverse effects and limited efficacy, driving interest in natural remedies like coumarin derivatives due to their diverse biological activities and perceived safety profile. This study focuses on the synthesis and characterization of a novel compound, 7-diethylamino-4-chloromethyl coumarin (referred to as 7D4C), derived from coumarin. Structural elucidation employed Fourier transform infrared spectroscopy (FT-IR), proton and carbon-13 nuclear magnetic resonance spectroscopy (¹H and ¹³C NMR), and mass spectrometry (MALDI-TOF-MS). Molecular docking studies were conducted to explore potential biological interactions. Furthermore, the anti-cancer potential of 7D4C was assessed using human epithelial adenocarcinom (LoVo) and healthy fibroblast (CCD-18Co) cell lines. Viability analysis, comet assay for DNA damage, and evaluation of cancer biomarkers including apoptosis, intracellular reactive oxygen species (iROS) levels, mitochondrial membrane potential (MMP), intracellular glutathione (GSH) concentration, and intracellular calcium (iCa²⁺) levels were performed. The synthesis of 7D4C was successfully completed, and its structure was confirmed. Molecular docking results indicate that 7D4C exhibits strong binding affinity to the p53 protein, highlighting its potential as a novel modulator of p53 activity. Subsequent investigations revealed that the synthesized compound induced apoptosis in cancer cells by reducing MMP and triggering DNA damage through the production of iROS. The promising anti-cancer activity of 7D4C in the LoVo cell line highlights its importance in coumarin-based therapies. Introducing 7D4C could significantly enhance future research in this area, leveraging insights from in vitro coumarin studies.