Virtual expedition into nature’s pharmacy: Unveiling promising anticancer compounds from Dendrophthoe falcata through in-silico exploration

Abstract

Cancer is a leading threatful disease worldwide. Research focused on natural compounds for anticancer drugs has facilitated the identification of numerous medications presently employed in cancer treatment. There is an ongoing need to create novel, potent, and cost-effective anticancer medications. In the present study, we have virtually investigated the potential anticancer activity of compounds namely nonadecan-1-ol, stigmast-4-en-3-one, 3β-hydroxylup-20(29)-en-28-oic acid, 7-hydroxy-4′,5,6-trimethoxyflavone, and 2,3-dihydro-4-hydroxy-3,6,9-trimethylnaphtho[1,8-bc]pyran-7,8-dione extracted from the natural source Dendrophthoe falcata against cancer-causing target proteins (cdk-2, p53, and caspase-9) using various in silico techniques, including molecular docking and simulation. Furthermore, drug-likeness, ADMET prediction, toxicity prediction, and DFT were performed to explore the toxicity and efficacy of therapeutic molecules. The present study is the first report of compounds known for their enormous biological applications from D. falcata, highlighting its novelty. The results revealed the highest negative binding affinity of 7-hydroxy-4′,5,6-trimethoxyflavone and 2,3-dihydro-4-hydroxy-3,6,9-trimethylnaphtho[1,8-bc]pyran-7,8-dione with all three target proteins. Additionally, cytotoxicity revealed the highest LD50 value, suggesting the lowest toxicity for the selected compounds. ADME analysis showed good responses in terms of solubility and absorption, supporting the drug-likeness of the proposed molecules. MD simulation and DFT results indicated the stability of the complex at a temperature of 298 K. The results concluded that the proposed molecules extracted from D. falcata have drug-like properties with tight and stable binding with the targeted proteins and might behave as potential anticancer agents.