Dataset Information

Cytotoxicity and molecular-docking approach of a new rosane-type diterpenoid from the roots of Euphorbia nematocypha.

ABSTRACT: A new rosane-type diterpenoid (1) along with nine known diterpenoids (2-10), were isolated from the dried roots of Euphorbia nematocypha. The absolute configuration was elucidated from spectroscopic (nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, and electronic circular dichroism) and optical-rotation analyses. Cytotoxicity and the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl radicals were determined. Compound 1 showed remarkable cytotoxicity against human cancer cell lines (HeLa, CT26, and HCC 1806) in vitro. The interaction between compound 1 and proteins of ribosomal S6 kinase was revealed using molecular docking and provided valuable insights into the cytotoxic mechanism of action of compound 1. The latter could be developed as a pharmaceutical agent in the future.

SUBMITTER: Song N

PROVIDER: S-EPMC9393309 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cytotoxicity and molecular-docking approach of a new rosane-type diterpenoid from the roots of Euphorbia nematocypha.

Song Nali N Zheng Xi X Wang Jiapeng J Zhu Li L Wang Chengyao C Cai Le L Ding Zhongtao Z

Frontiers in chemistry 20220808

A new rosane-type diterpenoid (1) along with nine known diterpenoids (2-10), were isolated from the dried roots of Euphorbia nematocypha. The absolute configuration was elucidated from spectroscopic (nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, and electronic circular dichroism) and optical-rotation analyses. Cytotoxicity and the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl radicals were determined. Compound 1 showed rema ...[more]

PMID: 36003622

Similar Datasets

Project description:Lepidium meyenii or Maca is widely cultivated as a health care food supplement due to its nutritional and medicinal properties. Although there are a few in-depth studies evaluating Maca antihypertensive effects, the correlations between the chemical constituents and bioactivity of the plant have not been studied before. Thus, the roots were extracted using different solvents (aqueous, methanol, 50% methanol, and methylene chloride) and investigated for their antihypertensive and antioxidant activities through several in vitro assays. The methanolic extract exhibited the best renin and angiotensin converting enzyme (ACE) inhibitory activities with IC50 values of 24.79 ± 1.3 ng/mL and 22.02 ± 1.1 ng/mL, respectively, along with the highest antioxidant activity. In total, 120 metabolites from different classes, e.g., alkylamides, alkaloids, glucosinolates, organic acids, and hydantoin derivatives, were identified in the methanolic extract using ultrahigh-performance liquid chromatography/high-resolution mass spectrometry (UPLC/HRMS). Molecular docking simulations were used to investigate the potential binding modes and the intermolecular interactions of the identified compounds with ACE and renin active sites. Glucotropaeolin, β-carboline alkaloids, succinic acid, and 2,4-dihydroxy-3,5-cyclopentyl dienoic acid showed the highest affinity to target the ACE with high docking scores (S ranging from -35.32 to -22.51 kcal mol-1) compared to lisinopril (S = -36.64 kcal mol-1). Interestingly, macamides displayed the greatest binding affinity to the active site of renin with docking scores (S ranging from -22.47 to -28.25 kcal mol-1). Further, β-carbolines achieved docking scores comparable to that of the native ligand (S ranging from -13.50 to -20.06 kcal mol-1). Molecular dynamics simulations and MMPBSA were also carried out and confirmed the docking results. Additionally, the computational ADMET study predicted that the compounds attaining promising docking results had proper pharmacokinetics, drug-likeness characteristics, and safe toxicological profiles. Ultimately, our findings revealed that Maca roots could be considered a promising candidate as an antihypertensive drug.

Project description:In this paper, we present the synthesis and characterization of two known sulfonyl hydrazides (1 and 2) and their new sulfonyl hydrazone derivatives (9-20), as well as in vitro and in silico investigations of their cytotoxic properties against human lung (A549) and human breast (MCF-7) cancer cell lines. The target compounds (9-20) obtained in high yields were synthesized for the first time by a multi-step reaction, and their structures were confirmed by elemental analysis and various spectral techniques, including FT-IR, 1H-, and 13C-NMR. The antiproliferative profiles of these compounds (1, 2, and 9-20) in this study were determined at concentrations of 200, 100, 50, and 25 µM against selected cancer cell lines for 72 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Except for compounds 1 and 2, other compounds (9-20) demonstrated cytotoxic activity at concentrations lower than 200 µM. The newly synthesized compounds (9-20) demonstrated antiproliferative activities at a micromolar level, with IC50 values in the range of 29.59-176.70 μM for the A549 cell line and 27.70-170.30 μM for the MCF-7 cell line. Among these compounds, compound 15 (IC50 = 29.59 μM against A549 cell line and IC50 = 27.70 μM against MCF-7 cell line) showed the highest cytotoxic activity against these two cancer cell lines compared to the reference drug cisplatin (IC50 = 22.42 μM against A549 cell line and IC50 = 18.01 μM against MCF-7 cell line). From docking simulations, to establish a plausible binding mode of compounds, we noticed that compound 15 demonstrated the highest affinity (-6.8508 kcal/mol) for estrogen receptor-beta (ERbeta) compared to others, suggesting promising ERbeta binding potential. Most compounds followed Lipinski's rule of five, with acceptable logP values. Additionally, all had mixed gastrointestinal absorption and limited blood-brain barrier permeability. Overall, our study proposed new sulfonyl hydrazones as a potential class of anticancer agents.

Dataset Information

Cytotoxicity and molecular-docking approach of a new rosane-type diterpenoid from the roots of Euphorbia nematocypha.

Publications

Cytotoxicity and molecular-docking approach of a new rosane-type diterpenoid from the roots of <i>Euphorbia nematocypha</i>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets