Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

In Silico Analysis of Compounds Derived from Perovskia Atriplicifolia for their Antidiabetic Potential

Author(s): Huma Aslam Butt, Hina Aslam Butt and Arif-ullah Khan*

Volume 16, Issue 9, 2019

Page: [1074 - 1088] Pages: 15

DOI: 10.2174/1570180815666181009130936

Price: $65

Abstract

Background: Diabetes is a chronic endocrine associated metabolic ailment. It is chiefly characterized by hyperglycemia, which results due to deficient insulin levels caused by either obliteration of pancreatic beta cells or the incompetent sensitivity of insulin at the target tissue.

Methods: In the present study, selected compounds (Abrotandiol, Abrotanone, Lariciresinol, Pinoresinol, Syringaresinol and Taxiresinol) from Perovskia atriplicifolia were evaluated for antidiabetic potentials using molecular docking simulations and computational tools.

Results: All selected compounds possess moderate to strong respective activities against aldose reductase, DPP-IV, PTPB, insulin receptor and PPAR-g. Selected compounds that include Abrotandiol, Lariciresinol, Pinoresinol, Syringaresinol, Abrotanone and Taxiresinol have shown highest binding energies of ΔG = -9.3 kcal/mol, -8.9 kcal/mol, -8.9 kcal/mol, -8.8 kcal/mol, -8.8 kcal/mol and -7.6 kcal/mol respectively against PPAR-g. However, out of six compounds, Abrotanone has shown strong potential binding energy against all selected targets, i.e. ΔG = -7.8 kcal/mol with aldose reductase, ΔG = -10.3 kcal/mol with DPP-IV, ΔG = -9.3 kcal/mol with PTPB and ΔG = -8.3 kcal/mol with insulin receptors.

Conclusion: The present study proposed that all selected compounds possess antidiabetic activity. However, Abrotanone has a strong antidiabetic potential. This assumption provides better insight to evaluate further these compounds for in vitro and in vivo testing against diabetes in future.

Keywords: Diabetes, phytoligands, target identification, docking simulation, Perovskia atriplicifolia, antidiabetic.

Graphical Abstract

[1]
Kahn, S.E. The importance of β-cell failure in the development and progression of type 2 diabetes. J. Clin. Endocrinol. Metab., 2001, 86, 4047-4058.http://press.endocrine.org/doi/10.1210/jcem.86.9.7713
[2]
Shaw, J.E.; Sicree, R.A.; Zimmet, P.Z. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res. Clin. Pract., 2010, 87, 4-14.http://www.ncbi.nlm.nih.gov/pubmed/19896746
[3]
Shera, A.S.; Jawad, F.; Maqsood, A. Prevalence of diabetes in Pakistan. Diabetes Res. Clin. Pract., 2007, 76, 219-222.http://www.diabetesresearchclinicalpractice.com/article/S0168822706003755/fulltext
[4]
Asano, T.; Ogihara, T.; Katagiri, H.; Sakoda, H.; Ono, H.; Fujishiro, M. Glucose transporter and Na+/glucose cotransporter as molecular targets of anti-diabetic drugs. Curr. Med. Chem., 2004, 11, 2717-2724.
[5]
Moller, D.E. New drug targets for type 2 diabetes and the metabolic syndrome. Nature, 2001, 414, 821-827.
[6]
Garber, A.J. Long-acting glucagon-like peptide 1 receptor agonists. Diabetes Care, 2011, 34.
[7]
Lavecchia, A.; Di Giovanni, C. Virtual screening strategies in drug discovery: A critical review. Curr. Med. Chem., 2013, 20, 2839-2860.http://www.ncbi.nlm.nih.gov/pubmed/23651302
[8]
Narayanaswamy, R.; Isha, A.; Wai, L.K.; Ismail, I.S. Molecular docking analysis of selected clinacanthus nutans constituents as xanthine oxidase, nitric oxide synthase, human neutrophil elastase, matrix metalloproteinase 2, matrix metalloproteinase 9 and squalene synthase inhibitors. Pharmacogn. Mag., 2016, 12, S21-S26.
[9]
Perveen, S.; Khan, S.B.; Malik, A.; Tareen, R.B.; Nawaz, S.A.; Choudhary, M.I. Phenolic constituents from Perovskia atriplicifolia. Nat. Prod. Res., 2006, 20, 347-353.
[10]
Tarawneh, A. León., F.; Pettaway, S.; Elokely, KM.; Klein, M.L.; Lambert, J. Mansoor, A.; Cutler, S.J. Flavonoids from Perovskia atriplicifolia and their in vitro displacement of the respective radioligands for human opioid and cannabinoid receptors. J. Nat. Prod., 2015, 78, 1461-1465.
[11]
Erdemgil, F.Z.; Ilhan, S.; Korkmaz, F.; Kaplan, C.; Mercangöz, A.; Arfan, M.; Ahmed, S. Chemical composition and biological activity of the essential oil of Perovskia atriplicifolia from Pakistan. Pharm. Biol., 2007, 45, 324-331.
[12]
Jiang, Z.Y.; Zhou, J.; Huang, C.G.; Hu, Q.F.; Huang, X.Z.; Wang, W.; Zhang, L-Z.; Li, G-P.; Xia, F-T. Two novel antiviral terpenoids from the cultured Perovskia atriplicifolia. Tetrahedron, 2015, 71, 3844-3849.
[13]
Ahmad, I.; Waheed, A.; Tahir, N.B.; Rais, A.K.; Rais, A.K. Anti-inflammatory constituents from Perovskia atriplicifolia. Pharm. Biol. Informa. Healthcare, 2015, 53, 1628-1631.[Available from: . http://www.tandfonline.com/doi/full/10.3109/13880209.2014.997250]
[14]
Khaliq, S.; Volk, F.J.; Frahm, A. Phytochemical investigation of Perovskia abrotanoides. Planta Med., 2007, 73, 77-83.
[15]
Liu, X.; Ouyang, S.; Yu, B. Liu. Y.; Huang, K.; Gong, J. Pharm Mapper server: A web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res., 2010, 38, 5-7.
[16]
Liang, J.; Edelsbrunner, H.; Woodward, C. Anatomy of protein pockets and cavities: Measurement of binding site geometry and implications for ligand design. Protein Sci., 1998, 7, 1884-1897.
[17]
Liang, J. Geometry of protein shape and its evolutionary pattern for function prediction and characterization. Conf. Proc. Annu. Int. Conf. IEEE. NIH Public Access, 2009, pp. 2324-2327.
[18]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46, 3-26.
[19]
Srimai, V.; Ramesh, M. Satya, Parameshwar, K.; Parthasarathy, T. Computer-aided design of selective Cytochrome P450 inhibitors and docking studies of alkyl resorcinol derivatives. Med. Chem. Res. Springer U.S., 2013, 22, 5314-5323.
[20]
Chang, L.C.W.; Spanjersberg, R.F. von, Frijtag, Drabbe.; Künzel, J.K.; Mulder-Krieger, T.; van den Hout, G.; Beukers, M.W.; Brussee, J.; Ijzerman, A.P.2, 4, 6-trisubstituted pyrimidines as a new class of selective adenosine A1 receptor antagonists. J. Med. Chem., 2004, 47, 6529-6540.
[21]
Ertl, P.; Rohde, B.; Selzer, P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J. Med. Chem., 2000, 43, 3714-3717.
[22]
Zhao, Y.H.; Abraham, M.H.; Le, J.; Hersey, A.; Luscombe, C.N.; Beck, G.; Sherborne, B.; Cooper, I. Rate-limited steps of human oral absorption and QSAR studies. Pharm. Res., 2002, 19, 1446-1457.
[23]
Clark, D.E. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1 Prediction of intestinal absorption. J. Pharm. Sci., 1999, 88, 807-814.
[24]
Muegge, I. Selection criteria for drug-like compounds. Med. Res. Rev., 2003, 23, 302-321.
[25]
Cheng, F.; Li, W.; Zhou, Y.; Shen, J.; Wu, Z.; Liu, G.; Lee, P.W.; Tang, Y. admetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties. J. Chem. Inf. Model., 2012, 52, 3099-3105.
[26]
Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Belew, R.K.; Olson, A.J. Automated docking using a lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem., 1998, 19, 1639-1662.
[27]
Liao, X.; Zhou, X.; Mak, N.; Leung, K. Tryptanthrin inhibits angiogenesis by targeting the VEGFR2-mediated ERK1/2 signalling pathway. PLoS One, 2013, 8e82294
[28]
Brahmkshatriya, P.P.; Brahmkshatriya, P.S. Terpenes: Chemistry, biological role, and therapeutic applications. Nat. Prod., 2013, 2665-2691.
[29]
Rao, D. Phytochemicals - A global perspective of their role in nutrition and health; In. Tech, 2012.
[30]
Veber, D.F.; Johnson, S.R.; Cheng, H.Y.; Smith, B.R.; Ward, K.W.; Kopple, K.D. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem., 2002, 45, 2615-2623.
[31]
Chung, T.D.Y.; Terry, D.B.; Smith, L.H. In vitroand in vivo assessment of ADME and PK properties during lead selection and lead optimization - guidelines, benchmarks and rules of thumb. assay guid. man. eli lilly & company and the national center for advancing translational sciences, 2004..

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy