Anti-inflammatory and anticancer activities of natural products and their derivatives

Abstract

Natural products have shown great potential due to their biological properties and their bioactive components, which demonstrate multiple mechanisms of action and lower cytotoxicity compared to conventional synthetic drugs. This dissertation focuses on the therapeutic potential of chamomile molecules (Matricaria chamomilla L.) and curcumin analogues (from Curcuma longa L), as anti-inflammatory and cancer preventive agents. In our investigations, an in silico virtual drug screening by molecular docking of 212 phytochemicals from chamomile revealed potential COX2 and NF-κB inhibitors, including β-amyrin, β-sitosterol, myricetin, lupeol, and quercetin. The in silico findings were validated through microscale thermophoresis and biochemical assays. The use of the various -omics facilitate the profiling of the bioactivity of these compounds. Furthermore, the bioinformatic analysis were then further verified through cytotoxicity assays using various cancer cell lines, and flow cytometric assays. These experiments allowed to demonstrate the potential to overcome resistance mechanisms associated with established anticancer drugs. In addition to evaluate their effect on modulating the reactive oxygen species generation and mitochondrial membrane potential. Moreover, the immunofluorescence microscopy of α-tubulin revealed significant correlations between the chamomile compounds myricetin, lupeol, and quercetin and vincristine, a well-established microtubule inhibitor. Notably, lupeol and quercetin induced G2/M cell cycle arrest and apoptosis. Further, western blot and RT-PCR assays were performed to highlights the involvement of the chamomile compounds in the regulation of immune response during inflammation. Similarly, an extensive analysis of 50 curcumin derivatives demonstrated their binding affinity to key cancer-related target proteins, including EGFR and NF-κB. The study indicated that several curcumin analogues had a stronger binding affinity than curcumin itself, suggesting that their derivatization could lead to improved target specificity and enhanced efficacy as anticancer agents. This was supported by a variety of bioactivity assays, including resazurin cell viability, assessment of oxidative stress and lactate dehydrogenase assays. In conclusion, our research highlights the ability of chamomile and curcumin derivatives to influence various biological processes within the cell and their therapeutic potential in treating inflammation and preventing cancer. Given the promising attributes of these natural products, it seems promising to further investigate them in in vitro and in vivo studies, as well as in clinical trials.