In Vitro and In Silico Cytotoxic and Antibacterial Activities of a Diterpene from Cousinia alata Schrenk

Almira Zhanzhaxina,Walter Luyten,Yerlan Suleimen,Ahmed M Metwaly,Eslam B Elkaeed,Kydyrmolla Akatan,Margarita Ishmuratova,Ibrahim H Eissa,Raigul Suleimen,Teodorico C Ramalho

doi:10.1155/2021/5542455

Almira Zhanzhaxina, Walter Luyten + Show 8 more

Open Access

https://doi.org/10.1155/2021/5542455

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Abstract

A biologically guided isolation of secondary metabolites from Cousinia alata Schrenk wild plant growing in Akmola region, Kazakhstan, led to the isolation of the bioactive diterpene grindelic acid (1). Six flavonoids were also isolated and identified as retusine (2), pachipodol (3), jaranol (4), penduletin (5), casticin (6), and 5, 7, 3′-trihydroxy-3, 4′-dimethoxyflavone (7). Penduletin (5) showed moderate cytotoxic activity assay. Grindelic acid exhibited promising cytotoxic activity against the Artemia salina nauplii and antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Salmonella enteritidis. The presence of the essential pharmacophoric features of histone deacetylase (HDAC) inhibitors in the structure of grindelic acid encouraged us to run a molecular docking study against the HDAC enzyme to understand its mechanism of action on a molecular level. Grindelic acid showed a binding mode of interaction similar to that of the cocrystallized ligand and exhibited good binding affinity against HDAC with the binding free energy of −18.70 kcal/mol. The structures of isolated compounds were determined by MS, 1D, and 2D NMR spectroscopy methods. Compounds (1–7) were isolated for the first time from Cousinia genus.

Highlights

Cancer is a disease that takes place in an organ or tissue of the body because of the uncontrolled growth of abnormal cells invading other parts inside the body and spreads to other tissues [1, 2]
Natural products can be considered as the main source of antimicrobial and anticancer compounds [5]. e activity of natural products either originated from plants [5,6,7], marines [8, 9] or fungi [10,11,12,13,14] is owned to a diversity of secondary metabolites that belong to various chemical classes such as flavonoids [15,16,17], saponins [6, 18], pyrones [19], isochromenes [20], and alkaloids [21]
About 56 species are distributed throughout Kazakhstan, including Cousinia alata Schrenk., which is a perennial plant, up to 50–90 cm high; its stems are straight, freely branched, naked, and winged; wings are with spinydentate margin; leaves are thin and simple; corolla is yellow or pink color

Summary

Introduction

Cancer is a disease that takes place in an organ or tissue of the body because of the uncontrolled growth of abnormal cells invading other parts inside the body and spreads to other tissues [1, 2]. The use of a histone deacetylase inhibitor in infected mice with M. tuberculosis inhibited bacterial growth, accelerated immune cell recruitment, induced proinflammatory cytokine expression, and suppressed IL-10 expression [41]. Another model of infected mice with E. coli treated with valproic acid (HDAC inhibitor) caused a noticeable decrease in bacterial load exaggeration and cytokine expression [42]. Grabiec et al reported the antibacterial effects of several HDAC inhibitors through different mechanisms [43]. Is study aims to isolate and identify the secondary metabolites which are responsible for the cytotoxic and antibacterial effects of Cousinia alata Schrenk extracts. Molecular docking studies have been preceded to have a better idea about the mechanism of action of the active compound on a molecular level

Experimental Part

Results and Discussion

Conclusions