epi-Magnolin, a tetrahydrofurofuranoid lignan from the oleo-gum resin of Commiphora wightii, as inhibitor of pancreatic cancer cell proliferation, in-vitro and in-silico study

Abstract

Five known furofuran lignans, dia-sesamin (1), 5-methoxysesamin (2), epi-magnolin (3), kobusin (4) and yangambin (5) were isolated for the first-time from the oleo-gum resin of Commiphora wightii. This is the first report on the ¹³C NMR assignments for epi-magnolin (3). Each of the isolated compounds was evaluated for its ability to inhibit MIA PaCa-2 pancreatic cancer cell line. Among them, epi-magnolin (3) displayed potential activity (IC₅₀ = 29 nM) compared to colchicine (IC₅₀ = 56 nM). 3D-flexible alignment revealed that epi-magnolin (3) has great matching with the tubulin polymerization inhibitor, colchicine. Meanwhile, docking studies exhibited that compounds 1–5 displayed good binding free energies against colchicine binding site (CBS) of tubulin with binding modes that were highly comparable to that of colchicine. Compounds 2, 3, and 5 showed superior binding free energies than colchicine (-24.37 kcal/mol). epi-Magnolin (3) showed the highest binding score against CBS. MD simulation studies confirmed the stability of epi-magnolin (3) in the active site for 200 ns. Furthermore, four online servers (Swiss ADME, pkCSM pharmacokinetics, AdmetSAR, and ProTox-II) were utilized to predict the ADMET parameters. The in-silico pharmacokinetics predictions reveled that epi-magnolin (3) has significant oral bioavailability and drug-like capabilities.

Communicated by Ramaswamy H. Sarma

Keywords:

• Commiphora wightii
• lignans
• (+)-epi-Magnolin
• colchicine binding site
• anti- pancreatic cancer
• flexible alignment
• docking
• molecular dynamic simulation

Acknowledgement

The authors would like to thank the authority of the Institute of Pharmaceutical and Drug Industries Research, National Research Centre, Egypt, for providing necessary chemicals, reagents and laboratory facilities for this research.

Compliance with ethical standard

This article does not contain any studies with human participants or animals performed by any of the authors.

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

Data availability statement

Data will be supplied upon request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.