Anti-inflammatory and cytotoxic specialised metabolites from the leaves of Glandularia × hybrida

Nesma M Mohamed; Mai A M Ahmed; Shabana I Khan; Frank R Fronczek; Anber F Mohammed; Samir A Ross

doi:10.1016/j.phytochem.2021.113054

Anti-inflammatory and cytotoxic specialised metabolites from the leaves of Glandularia × hybrida

Phytochemistry. 2022 Mar:195:113054. doi: 10.1016/j.phytochem.2021.113054. Epub 2021 Dec 31.

Authors

Nesma M Mohamed¹, Mai A M Ahmed¹, Shabana I Khan², Frank R Fronczek³, Anber F Mohammed⁴, Samir A Ross⁵

Affiliations

¹ Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
² National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA; Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
³ Department of Chemistry, Louisiana State University, Baton Rouge, LA, 70803, USA.
⁴ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
⁵ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA; Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA. Electronic address: sross@olemiss.edu.

PMID: 34979354
DOI: 10.1016/j.phytochem.2021.113054

Abstract

In our ongoing effort to investigate active specialised metabolites from genus Glandularia, phytochemical studies on the ethanolic extract of Glandularia × hybrida (Groenl. & Rümpler) G.L. Nesom & Pruski leaves resulted in the isolation of three undescribed compounds, a dibenzylbutyrolactolic lignan and two echinocystic acid based triterpenoid saponins, in addition to two known compounds. Interestingly, this study reports isolation of chemo-systematically valuable specialised metabolites for the first time from the genus under investigation. Additionally, the isolated metabolites were evaluated for their iNOS inhibition and cytotoxic activities using a combination of in silico and in vitro studies. The pharmacokinetics properties (ADMET) of some of the isolated compounds were determined using pkCSM-pharmacokinetics server. Molecular docking analysis showed that saponin compound possesses higher negative score (-9.59 kcal/mol) than the lignan compound (-6.56 kcal/mol). The isolated compounds also showed iNOS inhibition activity with IC₅₀ values ranging between 6.6 and 49.7 μM and significant cytotoxic activity against a series of cell lines including SK-MEL, KB, BT-549, SK-OV-3, LLC-PK1 and VERO cells. Hence, this study reveals that specialised metabolites from G. hybrida plant are of significant anti-inflammatory and cytotoxicity potentials.

Keywords: Glandularia × hybrida; Lignans; Molecular docking; Triterpenoidal saponins; Verbenaceae; X-ray crystallography; iNOS inhibition.

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology
Antineoplastic Agents, Phytogenic*
Chlorocebus aethiops
Molecular Docking Simulation
Plant Leaves
Verbenaceae*
Vero Cells

Substances

Anti-Inflammatory Agents
Antineoplastic Agents, Phytogenic