Molecular docking and dynamics simulations of bioactive terpenes from <i>Catharanthus roseus</i> essential oil targeting breast cancer

Abstract Background Medicinal plants have been used against diseases due to their protective and curative role since undocumented history. Approximately 50% of anticancer drugs are based on phytoconstituents of medicinal plants. Many bioactive substances with diverse pharmacological activities identified from Catharanthus roseus medicinal plant are actively used against cancer. Aim The aim of this study is to identify and analyze the potential of terpenes as natural inhibitors of breast cancer targeted receptors, which are required for identification of new compounds with enhanced specificity and improved efficacy. Understanding the potential of in silico interactions of selected terpene phytocompounds against breast cancer targets were assessed. Methods The selected identified terpenes from essential oil of Catharanthus roseus were assessed against estrogen receptor, progesterone receptor, and human epidermal growth factor receptor2 by molecular docking, molecular dynamic simulation analysis and by in vitro cytotoxicity analysis. Terpene phytocompounds, which have best docking affinity with breast cancer receptors, were preferable for further MD simulation study. Results After examining the pharmacokinetic characteristics and the outcomes of the toxicity prediction, it was shown that some selected terpene compounds have good potency without toxicity. According to the molecular dynamic simulations, the selected ligands demonstrated dynamical alteration for their particular initial positions at the protein’s catalytic site. The receptor–ligand complex similarly displayed minimal changes as compared to the free receptors. Thus, the terpene compounds are highlighted by these data as hits and potential leaders in the medicinal war against breast cancer. The absorption, distribution, metabolism, and excretion properties and AMES toxicity parameters were predicted using the Swiss-ADME system, while the bioavailability radar plots indicated relevant medicinal properties. Gamma terpinene, terpinen-4-ol, and limonene were therefore suggested as prospective lead compounds for additional research in the medication development process with breast cancer receptors against cancer. Conclusion These findings unequivocally demonstrate the high affinity of these terpene compounds for breast cancer targets, which further needs in vivo model testing and pre-clinical trials for cancer treatment.