Colorectal Cancer Chemoprevention by S-Allyl Cysteine–Caffeic Acid Hybrids: In Vitro Biological Activity and In Silico Studies

Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed at late stages, when the tumor has disseminated to other organs. Moreover, common observe that malignant cells may acquire resistance conventional chemotherapies through different mechanisms, including reducing drug activation or accumulation (by enhancing efflux), inducing alterations molecular targets, and inhibiting DNA damage response, among strategies. Considering these facts, discovery of new molecules with therapeutic potential become an invaluable tool chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET SAC-CAFA-PENT) exhibited selective cytotoxicity against SW480 cells, better results than chemotherapeutic agent (5-fluorouracil; 5-FU). Here, investigated possible mechanisms greater depth, identify whether they could be valuable scaffolds search chemopreventive treatment CRC. Both compounds reduced ROS formation, which related antioxidant effects. Further evaluations showed SAC-CAFA-MET induces cell death independent caspases tumor-suppressor protein p53, but probably mediated by negative regulation pro-apoptotic Bcl-2. addition, lack caspase-8 positive caspase-3 induced SAC-CAFA-PENT suggest compound acts apoptotic mechanism, initiated intrinsic pathways. Furthermore, downregulation IL-6 suggests also significant anti-inflammatory process. docking studies would modulation as primary mechanism elicits apoptosis SW480human adenocarcinoma cells. Meanwhile, density functional theory (DFT) calculations both produce effects via hydrogen atom transfer (HAT) pathway. The present work notes candidates further investigations agents.