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Pharmacognosy 2018
American Journal of Ethnomedicine
ISSN: 2348-9502
Page 80
April 16-17, 2018
Amsterdam, Netherlands
6
th
Edition of International Conference on
Pharmacognosy and
Medicinal Plants
Statement of the Problem:
The metabolic syndrome (MS)
represents a complex pathological condition featured by
hypertension, type 2 diabetes (T2D) and obesity. It is among the
risk factors for development of cardiovascular diseases (CVD)
and is characterized by increasing global prevalence. Modulation
of the nuclear peroxisome proliferator-activated receptor γ
(PPARγ) by natural compounds is considered a promising
pharmacological strategy for targeting the MS. Within this study,
we aimed at applying a virtual screening protocol for investigating
the potential of triterpenoid sapogenins of natural origin to act as
PPARγ partial agonists. Furthermore, an in silico estimation of
their safety profile has been performed.
Methodology & Theoretical Orientation:
An in-house virtual
library with more than 70 triterpenoids had been screened by
a pharmacophore-based docking of the unique aglycons in the
PPARγ binding pocket using MOE software (v.2016.0802). The
toxicity of these aglycons was evaluated using Derek Nexus
knowledge-based system (v.5.0.1.).
Findings:
Potential partial agonist-like binding modes were
evaluated based on the binding energy scores of the protein-
ligand (PL) complexes resulting from the docking simulation. The
PL interactions and poses relevant to the PPARγ partial agonists’
bindingpatternwere predicted. Potential toxicity effects, including
chromosome damage and developmental toxicity, were outlined
for particular triterpenoid aglycons.
Conclusion & Significance:
The results of this study contribute to
the mechanistic explanation at molecular level of the effects of
triterpenoid saponins/sapogenins by a potential PPARγ-mediated
mode of action. This research can direct further studies of
naturally-derived triterpenoids as potential MS modulators.
Recent Publications
1. Al Sharif M, Alov P, Diukendjieva A, Vitcheva V, Simeonova
R, et al. (2017) Molecular determinants of PPARγ partial
agonism and related
in silico/in vivo
studies of natural
saponins as potential type 2 diabetes modulators. Food
ChemToxicol 112:47–59.
2. Al Sharif M, Alov P, Vitcheva V, Diukendjieva A, Mori M, et
al. (2017) Natural modulators of nonalcoholic fatty liver
disease: Mode of action analysis and in silico ADME-Tox
prediction. Toxicol Appl Pharmacol 337:45–66.
3. Al Sharif M, Tsakovska I, Pajeva I, Alov P, Fioravanzo E, et
al. (2017) The application of molecular modelling in the
safety assessment of chemicals: A case study on ligand-
dependent PPARγ dysregulation. Toxicology 392:140–
154.
4. Tsakovska I, Al Sharif M, Alov P, Diukendjieva A,
Fioravanzo E, et al. (2014) Molecular modelling study
of the PPARγ receptor in relation to the mode of action/
adverse outcome pathway framework for liver steatosis.
Int J Mol Sci 15:7651–66.
5. Al Sharif M, Alov P, Vitcheva V, Pajeva I and Tsakovska
I (2014) Modes-of-action related to repeated dose
toxicity: tissue-specific biological roles of PPAR γ ligand-
dependent dysregulation in nonalcoholic fatty liver
disease. PPAR Res. 2014:432647.
In silico studies of plant triterpenoids: pharmacophore-based
virtual screening and toxicity evaluation
Antonia Diukendjieva
1
, Merilin Al Sharif
1
, Vessela Vitcheva
2
, Denitsa Aluani
2
,
Virginia Tzankova
2
, Petko Alov
1
, Ivanka Tsakovska
1
and
Ilza Pajeva
1
1
Bulgarian Academy of Sciences, Bulgaria
2
Medical University of Sofia, Bulgaria
Merilin Al Sharif et al., Am J Ethnomed 2018, Volume 5
DOI: 10.21767/2348-9502-C1-006