Computational studies of Salvurmin A and Salvurmin B, two ursane triterpenoids of Salvia Urmiensis as anti-cancer agents: molecular docking, molecular dynamic simulation, and DFT and ADMET analysis

Abstract

Salvurmin A and Salvurmin B are novel cytotoxic ursane triterpenoids isolated from Salvia urmiensis, an endemic plant species of Iran. The isolation, structure elucidation and in vitro anticancer properties of these two compounds were reported in our recent publications. For further studies, we assessed computational studies of Salvurmin A and Salvurmin B as anticancer agents. Molecular docking studies were performed to predict their affinity toward VEGFR-2 and Bcl-2 apoptosis regulator. Molecular dynamic simulation was also performed on the potent compound (Salvurmin B) to understand the virtual interaction in the active site of the enzyme (VEGFR-2). In addition, to obtain details of the structural properties of the compounds DFT analysis was performed. In order to better comprehend the reactivity of these molecules, the frontier orbitals were studied in detail, including HOMO–LUMO gap, molecular softness and hardness, electron affinity, chemical potential and electron surface potential studies. Taken together, Salvurmin B had desired chemical reactivity compared to Salvurmin A. In silico ADMET profiling calculations were also performed. Therefore, computational studies of the compounds in this study confirmed in vitro anticancer assessment in our recent report, and Salvurmin B can be considered as a potential candidate for further studies against human carcinoma cells.

GRAPHICAL ABSTRACT

KEYWORDS:

• Salvia urmiensis
• Salvurmin A and B
• computational studies
• MD simulation
• Molecular docking

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and materials

The data sets used and analysed during the current study are available from the corresponding author on reasonable request. We have presented all data in the form of Tables and Figures. The PDB codes (1Y6A and 6QGK) were retrieved from protein data bank (www.rcsb.org). https://www.rcsb.org/structure/1Y6A, and https://www.rcsb.org/structure/6QGK.

Authors’ contributions

Shima Hashemi prepared the manuscript and supervised the study. Hassan Seradj supervised the study. Saman Zare and Asieh Shahraki performed simulation study and wrote the simulation section. Marzieh Behrouz performed DFT analysis and wrote the DFT section. Leila Emami performed docking study and contributed to the preparation of the manuscript and supervised the study. All authors read and approved the final manuscript.

Additional information

Funding

Financial assistance from Shiraz University of Medical Sciences through grant number 15932 is gratefully acknowledged.