全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

Molecular Modeling Studies of Thiophenyl C-Aryl Glucoside SGLT2 Inhibitors as Potential Antidiabetic Agents

DOI: 10.1155/2014/739646

Full-Text   Cite this paper   Add to My Lib

Abstract:

A QSAR study on thiophenyl derivatives as SGLT2 inhibitors as potential antidiabetic agents was performed with thirty-three compounds. Comparison of the obtained results indicated the superiority of the genetic algorithm over the simulated annealing and stepwise forward-backward variable method for feature selection. The best 2D QSAR model showed satisfactory statistical parameters for the data set (, , and pred_) with four descriptors describing the nature of substituent groups and the environment of the substitution site. Evaluation of the model implied that electron-rich substitution position improves the inhibitory activity. The good predictive 3D-QSAR models by k-nearest neighbor (kNN) method for molecular field analysis (MFA) have cross-validated coefficient value of 0.7663 and predicted value of 0.7386. The results have showed that thiophenyl groups are necessary for activity and halogen, bulky, and less bulky groups in thiophenyl nucleus enhanced the biological activity. These studies are promising for the development of novel SGLT2 inhibitor, which may have potent antidiabetic activity. 1. Introduction One of the main features of diabetes is the elevation of blood sugar with its deleterious consequences in a variety of tissues [1]. Thus, control of the plasma glucose level is of utmost importance in the treatment of this disease. In recent years, the idea that affecting glucose absorption in the intestine and/or the glucose reabsorption in the kidney might be a possible way to control the sugar level has evolved. Diabetes comprises a group of metabolic disorders characterised by chronic hyperglycaemia with disorders in the metabolism of carbohydrate, fat, and protein that result in defects in secretion and action of insulin [2]. Dysfunction and failure of various organs, especially the eyes, kidneys, nerves, and heart, and the blood vessels are the usual complications of diabetes [3, 4]. Diabetes is mainly divided into four main types including insulin-dependent diabetes mellitus (type 1), non-insulin-dependent diabetes mellitus (type 2), gestational diabetes, and other specific types [5]. Diabetes mellitus type 2 (T2DM) accounts for almost 90% of diabetes cases, with the property of insulin resistance and beta-cell dysfunction that induces hyperglycemia [6]. Medical complications associated with T2DM include cardiovascular disease, stroke, nephropathy, retinopathy, renal failure, and amputations of the extremities [7]. In recent years, much attention has been given to sodium-dependent glucose cotransporters (SGLTs), mediators of reabsorption

References

[1]  A. Ceriello, “Proactive study: (r)evolution in the therapy of diabetes?” Diabetic Medicine, vol. 22, no. 11, pp. 1463–1464, 2005.
[2]  K. G. Alberti and P. Z. Zimmet, “Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation,” Diabetic Medicine, vol. 15, pp. 539–553, 1998.
[3]  V. Beletate, R. P. El Dib, and A. N. Atallah, “Zinc supplementation for the prevention of type 2 diabetes mellitus,” Cochrane Database of Systematic Reviews, vol. 1, Article ID CD005525, 2007.
[4]  T. Kuzuya, S. Nakagawa, J. Satoh et al., “Report of the Committee on the classification and diagnostic criteria of diabetes mellitus,” Diabetes Research and Clinical Practice, vol. 55, no. 1, pp. 65–85, 2002.
[5]  T. Kuzuya and A. Matsuda, “Classification of diabetes on the basis of etiologies versus degree of insulin deficiency,” Diabetes Care, vol. 20, no. 2, pp. 219–220, 1997.
[6]  D. Porte Jr., “Clinical importance of insulin secretion and its interaction with insulin resistance in the treatment of type 2 diabetes mellitus and its complications,” Diabetes/Metabolism Research and Reviews, vol. 17, pp. 181–188, 2001.
[7]  W. Zhang, A. Welihinda, J. Mechanic, et al., “EGT1442, a potent and selective SGLT2 inhibitor, attenuates blood glucose and HbA1c levels in db/db mice and prolongs the survival of stroke-prone rats,” Pharmacological Research, vol. 63, no. 4, pp. 284–293, 2011.
[8]  Y. Kanai, W. S. Lee, G. You, D. Brown, and M. A. Hediger, “The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal re-absorptive mechanism for D-glucose,” The Journal of Clinical Investigation, vol. 93, no. 1, pp. 397–404, 1994.
[9]  O. Marsenic, “Glucose control by the kidney: an emerging target in diabetes,” American Journal of Kidney Diseases, vol. 53, no. 5, pp. 875–883, 2009.
[10]  W. S. Lee, Y. Kanai, R. G. Wells, and M. A. Hediger, “The high affinity Na+/glucose cotransporter. Re-evaluation of function and distribution of expression,” The Journal of Biological Chemistry, vol. 269, no. 16, pp. 12032–12039, 1994.
[11]  B. Mackenzie, M. Panayotova-Heiermann, D. D. Loo, J. E. Lever, and E. M. Wright, “SAAT1 is a low affinity Na+/glucose cotransporter and not an amino acid transporter. A reinterpretation,” The Journal of Biological Chemistry, vol. 269, pp. 22488–22491, 1994.
[12]  E. M. Wright and E. Turk, “The sodium/glucose cotransport family SLC5,” Pflügers Archiv, vol. 447, no. 5, pp. 510–518, 2004.
[13]  K. Katsuno, Y. Fujimori, Y. Takemura et al., “Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level,” Journal of Pharmacology and Experimental Therapeutics, vol. 320, no. 1, pp. 323–330, 2007.
[14]  B. Mackenzie, D. D. Loo, M. Panayotova-Heiermann, and E. M. Wright, “Biophysical characteristics of the pig kidney Na+/glucose cotransporter SGLT2 reveal a common mechanism for SGLT1 and SGLT2,” The Journal of Biological Chemistry, vol. 271, no. 51, pp. 32678–32683, 1996.
[15]  W. N. Washburn, “Development of the renal glucose reabsorption inhibitors: a new mechanism for the pharmacotherapy of diabetes mellitus type 2,” Journal of Medicinal Chemistry, vol. 52, no. 7, pp. 1785–1794, 2009.
[16]  G. Toggenburger, M. Kessler, and G. Semenza, “Phlorizin as a probe of the small-intestinal Na+,d-glucose cotransporter. A model,” Biochimica et Biophysica Acta, vol. 688, no. 2, pp. 557–571, 1982.
[17]  A. Oku, K. Ueta, K. Arakawa et al., “Antihyperglycemic effect of T-1095 via inhibition of renal NA+-glucose cotransporters in streptozotocin-induced diabetic rats,” Biological and Pharmaceutical Bulletin, vol. 23, no. 12, pp. 1434–1437, 2000.
[18]  Y. Fujimori, K. Katsuno, K. Ojima et al., “Sergliflozin etabonate, a selective SGLT2 inhibitor, improves glycemic control in streptozotocin-induced diabetic rats and Zucker fatty rats,” European Journal of Pharmacology, vol. 609, no. 1–3, pp. 148–154, 2009.
[19]  Y. Fujimori, K. Katsuno, I. Nakashima, Y. Ishikawa-Takemura, H. Fujikura, and M. Isaji, “Remogliflozin etabonate, in a novel category of selective low-affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models,” Journal of Pharmacology and Experimental Therapeutics, vol. 327, no. 1, pp. 268–276, 2008.
[20]  L. Rossetti, D. Smith, G. I. Shulman, D. Papachristou, and R. A. DeFronzo, “Correction of hyperglycemia with phlorizin normalizes tissues sensitivity to insulin in diabetic rats,” Journal of Clinical Investigation, vol. 79, no. 5, pp. 1510–1515, 1987.
[21]  S. Kar and K. Roy, “Predictive toxicology using QSAR: a perspective,” Journal of the Indian Chemical Society, vol. 87, no. 12, pp. 1455–1515, 2010.
[22]  M. C. Sharma, D. V. Kohli, S. C. Chaturvedi, and S. Sharma, “Molecular modelling studies of some substitued 2-butylbenzimidazoles angiotensin II receptor antagonists as antihypertensive agents,” Digest Journal of Nanomaterials and Biostructures, vol. 4, no. 4, pp. 843–856, 2009.
[23]  M. C. Sharma, D. V. Kohli, N. K. Sahu, S. Sharma, and S. C. Chaturvedi, “2D-QSAR studies of some 1, 3, 4-thidiazole-2yl azetidine 2-one as antimicrobial activity,” Digest Journal of Nanomaterials and Biostructures, vol. 4, no. 2, pp. 339–347, 2009.
[24]  M. C. Sharma, D. V. Kohli, S. Sharma, and S. C. Chaturvedi, “Two dimensional-quantitative structure activity relationships -2, 3 diarylthiophenes as selective cox-1/-2 inhibitors,” Digest Journal of Nanomaterials and Biostructures, vol. 4, no. 3, pp. 459–469, 2009.
[25]  A. Dhakad, M. C. Sharma, S. C. Chaturvedi, and S. Sharma, “3D-QSAR studies, biological evaluation studies on some substituted 3-Chloro-1-[5-(5-chloro-2-phenyl-benzimidazole-1-ylmethyl)-[1, 3, 4] thiadiazole-2-yl]-azetidin-2-one as potential antimicrobial activity,” Digest Journal of Nanomaterials and Biostructures, vol. 4, no. 2, pp. 275–284, 2009.
[26]  M. C. Sharma, D. V. Kohali, N. K. Sahu, S. Sharma, and S. C. Chaturvedi, “QSAR, synthesis and biological activity studies of some thiazolidinones derivatives,” Digest Journal of Nanomaterials and Biostructures, vol. 4, no. 1, pp. 223–232, 2009.
[27]  M. C. Sharma, S. Sharma, P. Sharma, and A. Kumar, “Study of physicochemical properties-inducible nitric oxide synthase relationship of substituted quinazolinamines analogs: pharmacophore identification and QSAR studies,” Arabian Journal of Chemistry, 2013.
[28]  M. C. Sharma and D. V. Kohli, “An approach to design antihypertensive agents by 2D QSAR studies on series of substituted benzimidazoles derivatives as angiotensin II receptor antagonists,” Arabian Journal of Chemistry, 2011.
[29]  M. C. Sharma and D. V. Kohli, “QSAR analysis and 3D QSAR kNNMFA approach on a series of substituted quinolines derivatives as angiotensin II receptor antagonists,” Arabian Journal of Chemistry, 2011.
[30]  M. C. Sharma and D. V. Kohli, “QSAR studies on substituted benzimidazoles as angiotensin II receptor antagonists: kNN-MFA approach,” Arabian Journal of Chemistry, 2011.
[31]  M. C. Sharma and D. V. Kohli, “Two dimensional and k-Nearest neighbor molecular field analysis approach on substituted triazolone derivatives: an insight into the structural requirement for the angiotensin II receptor antagonist,” Journal of Saudi Chemical Society, 2011.
[32]  M. C. Sharma and D. V. Kohli, “QSAR analysis of imidazo [4,5-b] pyridine substituted a- phenoxyphenylacetic acids as angiotensin II AT1 receptor antagonists,” Journal of Saudi Chemical Society, 2011.
[33]  M. C. Sharma and D. V. Kohli, “Predicting substituted 2-butylbenzimidazoles derivatives as angiotensin II receptor antagonists: 3D-QSAR and pharmacophore modeling,” Journal of Saudi Chemical Society, 2011.
[34]  M. C. Sharma and D. V. Kohli, “3D QSAR studies of some substituted imidazolinones derivatives angiotensin II receptor antagonists,” World Applied Sciences Journal, vol. 12, no. 11, pp. 2129–2134, 2011.
[35]  M. C. Sharma and D. V. Kohli, “Exploration of quantitative structure activity relationship studies on a series of substituted quinazolinones as angiotensin II AT1 receptor antagonists,” World Applied Sciences Journal, vol. 12, no. 11, pp. 2111–2119, 2011.
[36]  M. C. Sharma and D. V. Kohli, “3D QSAR kNNMFA approach studies on series of substituted piperidin-2-one biphenyl tetrazoles as angiotensin II receptor antagonists,” American-Eurasian Journal of Toxicological Sciences, vol. 3, pp. 75–84, 2011.
[37]  M. C. Sharma and D. V. Kohli, “3D QSAR approach on substituted isoxazolidines derivatives as angiotensin II receptor antagonist,” American-Eurasian Journal of Toxicological Sciences, vol. 3, no. 2, pp. 85–91, 2011.
[38]  M. C. Sharma and D. V. Kohli, “2D- and 3D- QSAR studies of substituted 4H-pyrido [1, 2-a] pyrimidin-4-ones angiotensin II receptor antagonists,” European Journal of Toxicological Sciences, vol. 3, pp. 92–100, 2011.
[39]  M. C. Sharma, “Structural insight for (6-oxo-3-pyridazinyl)-benzimidazoles derivatives as angiotensin II receptor antagonists: QSAR, pharmacophore identification and kNNMFA approach,” Journal of Saudi Chemical Society, 2012.
[40]  M. C. Sharma and D. V. Kohli, “A comprehensive structure-activity analysis of 5-Carboxyl Imidazolyl biphenyl Sulfonylureas derivatives angiotensin AT1 receptor antagonists: 2D- and 3D-QSAR approach,” Arabian Journal of Chemistry, 2012.
[41]  M. C. Sharma and D. V. Kohli, “Comprehensive structure-activity relationship analysis of isoxazolinyl and isoxazolidinyl substituted quinazolinone derivatives as angiotensin II receptor antagonists,” Journal of Saudi Chemical Society, 2012.
[42]  M. C. Sharma and D. V. Kohli, “QSAR analysis of 2-alkyl-4-(biphenylmethoxy) quinolines as angiotensin II receptor antagonists,” Oxidation Communications, vol. 35, no. 4, pp. 928–944, 2012.
[43]  M. C. Sharma and D. V. Kohli, “Insight into the structural requirement of aryltriazolinone derivatives as angiotensin II AT1 receptor: 2D and 3D-QSAR k-nearest neighbor molecular field analysis approach,” Medicinal Chemistry Research, vol. 21, no. 10, pp. 2837–2853, 2012.
[44]  M. C. Sharma and D. V. Kohli, “Predicting 2,3-Dihydroquinazolinonesderivatives as angiotensin II receptor antagonists: 2D QSAR approach,” Oxidation Communications, vol. 35, no. 3, pp. 722–734, 2012.
[45]  M. C. Sharma, S. Sharma, and D. V. Kohlp, “Qsar approach insight the structural requirement of substituted quinazolinones derivatives as angiotensin ii receptor antagonists,” Oxidation Communications, vol. 35, no. 3, pp. 694–707, 2012.
[46]  M. C. Sharma, S. Sharma, and D. V. Kohli, “Qsar studies of 2-alkylbenzimidazole derivatives as angiotensin ii receptor antagonists,” Oxidation Communications, vol. 35, no. 3, pp. 708–721, 2012.
[47]  M. C. Sharma, S. Sharma, and K. S. Bhadoriya, “QSAR analyses and pharmacophore studies of tetrazole and sulfonamide analogs of imidazo[4,5-b]pyridine using simulated annealing based feature selection,” Journal of Saudi Chemical Society, 2012.
[48]  M. C. Sharma and D. V. Kohli, “Rationalization of 2-alkylbenzimidazoles bearing a N-phenyl pyrrole moiety as novel Angiotensin II AT1 receptor antagonists—a QSAR approach,” Oxidation Communications, vol. 36, no. 1, pp. 190–204, 2013.
[49]  M. C. Sharma and D. V. Kohli, “Quantitative structure-activity relationship analysis of series of substituted piperidin-2-one biphenyl tetrazoles analogues as novel angiotensin ii receptor antagonists,” Oxidation Communications, vol. 36, no. 1, pp. 176–189, 2013.
[50]  M. C. Sharma and D. V. Kohli, “A comprehensive structure-activity analysis 2,3,5-trisubstituted 4,5-dihydro-4-oxo-3H-imidazo [4,5-c] pyridine derivatives as angiotensin II receptor antagonists: using 2D- and 3D-QSAR approach,” Medicinal Chemistry Research, vol. 22, no. 2, pp. 588–605, 2013.
[51]  M. C. Sharma and D. V. Kohli, “Comprehensive two and three-dimensional QSAR studies of 3-substituted 6-butyl-1,2dihydropyridin-2-ones derivatives as angiotensin II receptor antagonists,” Medicinal Chemistry Research, vol. 22, no. 3, pp. 1107–1123, 2013.
[52]  M. C. Sharma, “Structural requirements of some 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide derivatives as poly (ADP-ribose) polymerase (PARP) for the treatment of cancer: QSAR approach,” Interdisciplinary Sciences: Computational Life Sciences, 2014.
[53]  M. C. Sharma, S. Sharma, N. K. Sahu, and D. V. Kohli, “QSAR studies of some substituted imidazolinones angiotensin II receptor antagonists using Partial Least Squares Regression (PLSR) method based feature selection,” Journal of Saudi Chemical Society, vol. 17, no. 2, pp. 219–225, 2013.
[54]  M. C. Sharma, “Discovery of potent antihypertensive ligands substituted imidazolyl biphenyl sulfonylureas analogs as angiotensin II AT1 receptor antagonists by molecular modelling studies,” Interdisciplinary Sciences: Computational Life Sciences, 2014.
[55]  M. C. Sharma, D. V. Kohli, and S. Sharma, “Molecular modeling studies of substituted 2,4,5-trisubstituted triazolinones aryl and nonaryl derivatives as angiotensin II AT1 receptor antagonists,” Journal of Chemistry, vol. 2013, Article ID 427181, 14 pages, 2013.
[56]  M. C. Sharma, “Discovery of new lead pyrimidines derivatives as potential cannabinoid CB1 receptor antagonistic through molecular modeling and pharmacophore approach,” Medicinal Chemistry Research, vol. 23, no. 5, pp. 2287–2311, 2014.
[57]  M. C. Sharma, “Comparative pharmacophore modeling and QSAR studies for structural requirements of some substituted 2-aminopyridines derivatives as inhibitors nitric oxide synthases,” Interdisciplinary Sciences: Computational Life Sciences, 2014.
[58]  M. C. Sharma, “A structure-activity relationship study of imidazole-5-carboxylic acids derivatives as angiotensin II receptor antagonists combining 2D and 3D QSAR methods,” Interdisciplinary Sciences: Computational Life Sciences, 2014.
[59]  M. C. Sharma, S. Sharma, P. Sharma, A. Kumar, and K. S. Bhadoriya, “Structural insights for substituted acyl sulfonamides and acyl sulfamides derivatives of imidazole as angiotensin II receptor antagonists using molecular modeling approach,” Journal of the Taiwan Institute of Chemical Engineers, vol. 45, no. 1, pp. 12–23, 2014.
[60]  M. C. Sharma, “Molecular modelling studies for the discovery of new substituted pyridines derivatives with angiotensin II AT1 receptor antagonists,” Interdisciplinary Sciences, Computational Life Sciences, vol. 6, no. 3, pp. 197–207, 2014.
[61]  M. C. Sharma, S. Sharma, N. K. Sahu, and D. V. Kohli, “3D QSAR kNN-MFA studies on 6-substituted benzimidazoles derivatives as nonpeptide angiotensin II receptor antagonists: a rational approach to antihypertensive agents,” Journal of Saudi Chemical Society, vol. 17, no. 2, pp. 167–176, 2013.
[62]  M. C. Sharma, “Prospective QSAR-based prediction models with pharmacophore studies of oxadiazole-substituted α-isopropoxy phenylpropanoic acids on with dual activators of PPARα and PPARγ,” Interdisciplinary Sciences: Computational Life Sciences, 2014.
[63]  M. C. Sharma, S. Sharma, P. Sharma, and A. Kumar, “Pharmacophore and QSAR modeling of some structurally diverse azaaurones derivatives as anti-malarial activity,” Medicinal Chemistry Research, vol. 23, no. 1, pp. 181–198, 2014.
[64]  M. C. Sharma, “Rationalization of physicochemical characters and pharmacophore approach of 3-(4-biphenylmethyl) 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridines analogs toward angiotensin II AT receptor antagonists,” Interdisciplinary Sciences: Computational Life Sciences. In press.
[65]  M. C. Sharma, “Molecular modeling studies of substituted 3,4-dihydroxychalcone derivatives as 5-lipoxygenase and cyclooxygenase inhibitors,” Medicinal Chemistry Research, vol. 23, no. 4, pp. 1797–1818, 2014.
[66]  M. C. Sharma, “A structure-activity relationship study of naphthoquinone derivatives as antitubercular agents using molecular modelling techniques,” Interdisciplinary Sciences: Computational Life Sciences. In press.
[67]  M. C. Sharma, “Identification of 3-nitro-2, 4, 6-trihydroxybenzamide derivatives as photosynthetic electron transport inhibitors by QSAR and pharmacophore studies,” Interdisciplinary Sciences: Computational Life Sciences, 2014.
[68]  S. H. Lee, K. S. Song, J. Y. Kim et al., “Novel thiophenyl C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents,” Bioorganic and Medicinal Chemistry, vol. 19, no. 19, pp. 5813–5832, 2011.
[69]  VLife MDS 3.5, Molecular Design Suite, Vlife Sciences Technologies Pvt. Ltd., Pune, India, 2008, http://www.vlifesciences.com/.
[70]  T. A. Halgren, “Merck molecular force field. III. Molecular geometries and vibrational frequencies for MMFF94,” Journal of Computational Chemistry, vol. 17, no. 5-6, pp. 553–586, 1996.
[71]  A. Golbraikh and A. Tropsha, “Predictive QSAR modeling based on diversity sampling of experimental datasets for the training and test set selection,” Journal of Computer-Aided Molecular Design, vol. 16, no. 5-6, pp. 357–369, 2002.
[72]  S. Ajmani, K. Jadhav, and S. A. Kulkarni, “Three-dimensional QSAR using the k-nearest neighbor method and its interpretation,” Journal of Chemical Information and Modeling, vol. 46, no. 1, pp. 24–31, 2006.
[73]  R. D. Cramer III, D. E. Patterson, and J. D. Bunce, “Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins,” Journal of the American Chemical Society, vol. 110, no. 18, pp. 5959–5967, 1988.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133