Analysis and prediction pathways of natural products and their cytotoxicity against HeLa cell line protein using docking, molecular dynamics and ADMET

Natural product such as flavonoids and their derivatives have a discernible capability to inhibit tumor formation and the growth of cancer cell, which have a vital link between diet and chronic disease prevention. Several plants and spices that contain flavonoid derivatives have been used in traditional medicine as disease preventative and therapeutic agents. Therefore, flavonoids could be used as chemotherapeutic drugs, indicating their potential clinical utility in cancer treatment. The purpose of this research was to discover and produce innovative pharmaceuticals from natural sources by introducing structural changes into flavonoids' backbones and changing their structures to improve biological activity and anticancer effects. In the current study, it was expected that the percent unbound values for the 15 compounds in human plasma would be low, ranging between 0.188 and 0.391. However, all compounds have a safe range and are not toxic to the brain. Compounds 2, 10, and 13 were shown to be permeable to the CNS (log PS > -3), but all other compounds had difficulty penetrating the CNS. Furthermore, all compounds had a low total clearance, ranging from 0.038 to 1.216 ml/min/kg, indicating that these compounds have a long half-life. None of the compounds caused skin sensitization (SS), and only compounds 1, 11, and 12 are expected to be AMES-positive, suggesting that the other compounds are not mutagenic. The result of the study showed based on the Drug-likeness and ADMET studies, only 3 compounds, including 3, 4, and 15, have a good pharmacokinetics propriety, the lowest toxicity, and good binding affinity towards Caspase 3 V266APDB (ID: 5I9B) as potential inhibitor candidates for the HeLa cell line, they have a low total clearance property and no AMES mutagenicity or hERG inhibition properties. These compounds (3,4,15) were examined to act as new cytotoxic drug candidates and would have an interest as starting point for designing compounds against the HeLa cell line. Communicated by Ramaswamy H. Sarma