Molecular Docking and Pharmacophore Analysis of Trisindoline 1 Against Human Topoisomerase II and Human Derived Growth Factor

Liver cancer is currently a leading cause of death worldwide and its incidence is increasing. As a result, there has been an increase in the development of computational drug design strategies utilizing molecules for anti-cancer candidates over the last decade. DNA topoisomerase II (topo II) enzymes play a crucial role in regulating essential cellular processes by altering the topology of chromosomal DNA. The PDGF receptor is a promising anti-cancer target and is used as a prognostic marker for liver cancer due to its ability to interact with topo II enzymes. Trisindoline 5'-nitro- [3,3 ': 3', 3”-terindoline] -2'-one is a cytotoxic indole trimer alkaloid compound that induces apoptosis in the HepG2 cell line. This study investigated the potential of Trisindoline 1 as an alternative drug for liver cancer by conducting molecular docking against topo II and PDGF. The binding energy value of Trisindoline 1 against human topo II was -10.1 Kcal/mol, which was higher than the binding energy value of doxorubicin (-9.2 Kcal/mol). Furthermore, pharmacophore analysis of Trisindoline 1 indicated that it possesses drug-like properties and lower toxicity than doxorubicin. Trisindoline 1 has the potential to inhibit PDGF and human topo II enzymes in liver cancer through the apoptotic pathway.