Metabolomic profile, anti-trypanosomal potential and molecular docking studies of Thunbergia grandifolia

Heba A S El-Nashar; Ahmed M Sayed; Hany A M El-Sherief; Mostafa E Rateb; Lina Akil; Ibrahim Khadra; Taghreed A Majrashi; Sara T Al-Rashood; Faizah A Binjubair; Mahmoud A El Hassab; Wagdy M Eldehna; Usama Ramadan Abdelmohsen; Nada M Mostafa

doi:10.1080/14756366.2023.2199950

Metabolomic profile, anti-trypanosomal potential and molecular docking studies of Thunbergia grandifolia

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2199950. doi: 10.1080/14756366.2023.2199950.

Authors

Affiliations

¹ Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
² Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, Minia, Egypt.
⁴ School, of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley, UK.
⁵ Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, UK.
⁶ Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
⁷ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
⁸ Department of Medicinal Chemistry, Faculty of Pharmacy, King Salman International University (KSIU), Ras Sudr, Egypt.
⁹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt.
¹⁰ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt.
¹¹ Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, Universities Zone, New Minia City, Egypt.

Abstract

Trypanosomiasis is a protozoan disease transmitted via Trypanosoma brucei. This study aimed to examine the metabolic profile and anti-trypanosomal effect of methanol extract of Thunbergia grandifolia leaves. The liquid chromatography-high resolution electrospray ionisation mass spectrometry (LC-HRESIMS) revealed the identification of fifteen compounds of iridoid, flavonoid, lignan, phenolic acid, and alkaloid classes. The extract displayed a promising inhibitory activity against T. brucei TC 221 with MIC value of 1.90 μg/mL within 72 h. A subsequent in silico analysis of the dereplicated compounds (i.e. inverse docking, molecular dynamic simulation, and absolute binding free energy) suggested both rhodesain and farnesyl diphosphate synthase as probable targets for two compounds among those dereplicated ones in the plant extract (i.e. diphyllin and avacennone B). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling of diphyllin and avacennone were calculated accordingly, where both compounds showed acceptable drug-like properties. This study highlighted the antiparasitic potential of T. grandifolia leaves.

Keywords: LC-MS; Thunbergia grandifolia; Trypanosoma brucei; in silico; inverse docking.

MeSH terms

Acanthaceae*
Lignans* / pharmacology
Molecular Docking Simulation
Plant Extracts / chemistry
Plant Extracts / pharmacology
Trypanosoma brucei brucei*

Substances

diphyllin
Lignans
Plant Extracts

Grants and funding

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through Small Groups Project under grant number (RGP.1/346/43). The authors acknowledge financial support from the Researchers Supporting Project number (RSP-2023/103), King Saud University, Riyadh, Saudi Arabia.