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

Mohamed H Abd El-Razek; Ibrahim H Eissa; Ahmed A Al-Karmalawy; Ahmed A Elrashedy; Ahmed H El-Desoky; Mohamed Aboelmagd; Tarik A Mohamed; Mohamed-Elamir F Hegazy

doi:10.1080/07391102.2024.2308767

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

J Biomol Struct Dyn. 2024 Jan 24:1-13. doi: 10.1080/07391102.2024.2308767. Online ahead of print.

Authors

Mohamed H Abd El-Razek¹, Ibrahim H Eissa², Ahmed A Al-Karmalawy^{3

4}, Ahmed A Elrashedy⁵, Ahmed H El-Desoky⁶, Mohamed Aboelmagd⁶, Tarik A Mohamed⁷, Mohamed-Elamir F Hegazy⁷

Affiliations

¹ Chemistry of Natural Compounds Department, Institute of Pharmaceutical and Drug Industries Research, National Research Centre (NRC), Giza, Egypt.
² Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, Egypt.
⁴ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza, Egypt.
⁵ Department of the Chemistry of Natural and Microbial Products, Pharmaceutical and Drug Industries Institute, National Research Centre (NRC), Giza, Egypt.
⁶ Pharmacognosy Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre (NRC), Giza, Egypt.
⁷ Chemistry of Medicinal Plants Department, Institute of Pharmaceutical and Drug Industries Research, National Research Centre (NRC), Giza, Egypt.

PMID: 38265952
DOI: 10.1080/07391102.2024.2308767

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