Login Register Cart 0
Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

In Silico Design, Synthesis and Evaluation of Novel Series of Benzothiazole- Based Pyrazolidinediones as Potent Hypoglycemic Agents

Author(s): Michelyne Haroun*

Volume 16, Issue 6, 2020

Page: [812 - 825] Pages: 14

DOI: 10.2174/1573406416666191227113716

Price: $65

Abstract

Background: The discovery of novel ligand binding domain (LBD) of peroxisome proliferator- activated receptor γ (PPARγ) has recently attracted attention to few research groups in order to develop more potent and safer antidiabetic agents.

Objective: This study is focused on docking-based design and synthesis of novel compounds combining benzothiazole and pyrazolidinedione scaffold as potential antidiabetic agents.

Methods: Several benzothiazole-pyrazolidinedione hybrids were synthesized and tested for their in vivo anti-hyperglycemic activity. Interactions profile of title compounds against PPARγ was examined through molecular modelling approach.

Results: All tested compounds exhibited anti-hyperglycemic activity similar or superior to the reference drug Rosiglitazone. Introducing chlorine atom and alkyl group at position-6 and -5 respectively on benzothiazole core resulted in enhancing the anti-hyperglycemic effect. Docking study revealed that such groups demonstrated favorable hydrophobic interactions with novel LBD Ω- pocket of PPARγ protein.

Conclusion: Among the tested compounds, N-(6-chloro-5-methylbenzo[d]thiazol-2-yl-4-(4((3,5- dioxopyrazolidin-4-ylidene)methyl)phenoxy)butanamide 5b was found to be the most potent compound and provided valuable insights to further develop novel hybrids as anti-hyperglycemic agents.

Keywords: Benzothiazole, pyrazolidinedione, PPARγ inhibitor, Ω-pocket binding domain, In silico evaluation, Antihyperglycemic activity.

« Previous Next »
Graphical Abstract

[1]
Unnikrishnan, R.; Pradeepa, R.; Joshi, S.R.; Mohan, V. Type 2 Diabetes: Demystifying the Global Epidemic. Diabetes, 2017, 66(6), 1432-1442.
[http://dx.doi.org/10.2337/db16-0766] [PMID: 28533294]
[2]
Forouhi, N.G.; Misra, A.; Mohan, V.; Taylor, R.; Yancy, W. Dietary and nutritional approaches for prevention and management of type 2 diabetes. BMJ, 2018, 361, k2234.
[http://dx.doi.org/10.1136/bmj.k2234] [PMID: 29898883]
[3]
Baynes, H.W. Classification, Pathophysiology, Diagnosis and Management of Diabetes Mellitus. J. Diabetes Metab., 2015, 6(5), 1-9.
[4]
Chen, C.; Cohrs, C.M.; Stertmann, J.; Bozsak, R.; Speier, S. Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis. Mol. Metab., 2017, 6(9), 943-957.
[http://dx.doi.org/10.1016/j.molmet.2017.06.019] [PMID: 28951820]
[5]
Röder, P.V.; Wu, B.; Liu, Y.; Han, W. Pancreatic regulation of glucose homeostasis. Exp. Mol. Med., 2016, 48(3), e219-e219.
[http://dx.doi.org/10.1038/emm.2016.6] [PMID: 26964835]
[6]
Oh, Y.S.; Bae, G.D.; Baek, D.J.; Park, E.Y.; Jun, H.S. Fatty acid induced lipotoxicity in pancreatic beta-cells during development of type 2 diabetes. Front. Endocrinol., 2018, 9384, 1-10.
[7]
Rachdaoui, N.; Polo-Parada, L.; Ismail-Beigi, F. Prolonged Exposure to Insulin Inactivates Akt and Erk1/2 and Increases Pancreatic Islet and INS1E β-Cell Apoptosis. J. Endocr. Soc., 2018, 3(1), 69-90.
[http://dx.doi.org/10.1210/js.2018-00140] [PMID: 30697602]
[8]
Chawla, A.; Chawla, R.; Jaggi, S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J. Endocrinol. Metab., 2016, 20(4), 546-551.
[http://dx.doi.org/10.4103/2230-8210.183480] [PMID: 27366724]
[9]
Chew, B-H.; Fernandez, A.; Shariff-Ghazali, S. Psychological interventions for behavioral adjustments in diabetes care - a value-based approach to disease control. Psychol. Res. Behav. Manag., 2018, 11, 145-155.
[http://dx.doi.org/10.2147/PRBM.S117224] [PMID: 29765258]
[10]
Tratrat, C.; Haroun, M.; Paparisva, A.; Geronikaki, A.; Kamoutsis, C.; Ćirić, A.; Glamočlija, J.; Soković, M.; Fotakis, C.; Zoumpoulakis, P.; Bhunia, S.S.; Saxena, A.K. Design, synthesis and biological evaluation of new substituted 5-benzylideno-2-adamantylthiazol[3,2-b][1,2,4]triazol-6(5H)ones. Pharmacophore models for antifungal activity. Arab. J. Chem., 2018, 11(4), 573-590.
[http://dx.doi.org/10.1016/j.arabjc.2016.06.007]
[11]
Snell-Bergeon, J.K.; Wadwa, R. Hypoglycemia, diabetes, and cardiovascular disease. Diab. Technol. Therapeut., 2012, 14(Suppl. 1), S51-S58.
[http://dx.doi.org/10.1089/dia.2012.0031]
[12]
Verhulst, M.J.L.; Loos, B.G.; Gerdes, V.E.A.; Teeuw, W.J. Evaluating all potential oral complications of diabetes mellitus. Front. Endocrinol., 2019, 10, 1-49.56.
[13]
Chew, B-H.; Shariff-Ghazali, S.; Fernandez, A. Psychological aspects of diabetes care: Effecting behavioral change in patients. World J. Diabetes, 2014, 5(6), 796-808.
[http://dx.doi.org/10.4239/wjd.v5.i6.796] [PMID: 25512782]
[14]
Patti, G.; Cavallari, I.; Andreotti, F.; Calabrò, P.; Cirillo, P.; Denas, G.; Galli, M.; Golia, E.; Maddaloni, E.; Marcucci, R.; Parato, V.M.; Pengo, V.; Prisco, D.; Ricottini, E.; Renda, G.; Santilli, F.; Simeone, P.; De Caterina, R. Working Group on Thrombosis of the Italian Society of Cardiology. Prevention of atherothrombotic events in patients with diabetes mellitus: from antithrombotic therapies to new-generation glucose-lowering drugs. Nat. Rev. Cardiol., 2019, 16(2), 113-130.
[http://dx.doi.org/10.1038/s41569-018-0080-2] [PMID: 30250166]
[15]
Choudhury, H.; Pandey, M.; Hua, C.K.; Mun, C.S.; Jing, J.K.; Kong, L.; Ern, L.Y.; Ashraf, N.A.; Kit, S.W.; Yee, T.S.; Pichika, M.R.; Gorain, B.; Kesharwani, P. An update on natural compounds in the remedy of diabetes mellitus: A systematic review. J. Tradit. Complement. Med., 2017, 8(3), 361-376.
[http://dx.doi.org/10.1016/j.jtcme.2017.08.012] [PMID: 29992107]
[16]
Garcia-Vallvé, S.; Guasch, L.; Tomas-Hernández, S.; del Bas, J.M.; Ollendorff, V.; Arola, L.; Pujadas, G.; Mulero, M. Peroxisome Proliferator-Activated Receptor γ (PPARγ) and Ligand Choreography: Newcomers Take the Stage. J. Med. Chem., 2015, 58(14), 5381-5394.
[http://dx.doi.org/10.1021/jm501155f] [PMID: 25734377]
[17]
Soccio, R.E.; Chen, E.R.; Lazar, M.A. Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes. Cell Metab., 2014, 20(4), 573-591.
[http://dx.doi.org/10.1016/j.cmet.2014.08.005] [PMID: 25242225]
[18]
Desai, N.C.; Pandit, U.P.; Dodiya, A. Thiazolidinedione compounds: a patent review (2010 - present). Expert Opin. Ther. Pat., 2015, 25(4), 479-488.
[http://dx.doi.org/10.1517/13543776.2014.1001738] [PMID: 25579106]
[19]
He, J.; Xu, C.; Kuang, J.; Liu, Q.; Jiang, H.; Mo, L.; Geng, B.; Xu, G. Thiazolidinediones attenuate lipolysis and ameliorate dexamethasone-induced insulin resistance. Metabolism, 2015, 64(7), 826-836.
[http://dx.doi.org/10.1016/j.metabol.2015.02.005] [PMID: 25825274]
[20]
Majithia, A.R.; Tsuda, B.; Agostini, M.; Gnanapradeepan, K.; Rice, R.; Peloso, G.; Patel, K.A.; Zhang, X.; Broekema, M.F.; Patterson, N.; Duby, M.; Sharpe, T.; Kalkhoven, E.; Rosen, E.D.; Barroso, I.; Ellard, S.; Kathiresan, S.; O’Rahilly, S.; Chatterjee, K.; Florez, J.C.; Mikkelsen, T.; Savage, D.B.; Altshuler, D. UK Monogenic Diabetes Consortium. Myocardial Infarction Genetics Consortium; UK Congenital Lipodystrophy Consortium. Prospective functional classification of all possible missense variants in PPARG. Nat. Genet., 2016, 48(12), 1570-1575.
[http://dx.doi.org/10.1038/ng.3700] [PMID: 27749844]
[21]
Medicine, U.P.S.o. Available at:. https://www.sciencedaily.com/releases/2019/01/190110141816.htm2019.
[22]
Fukunaga, T.; Zou, W.; Rohatgi, N.; Colca, J.R.; Teitelbaum, S.L. An insulin-sensitizing thiazolidinedione, which minimally activates PPARγ, does not cause bone loss. J. Bone Miner. Res., 2015, 30(3), 481-488.
[23]
Hong, F.; Xu, P.; Zhai, Y. The opportunities and challenges of peroxisome proliferator-activated receptors ligands in clinical drug discovery and development. Int. J. Mol. Sci., 2018, 19(8), 1-29.
[http://dx.doi.org/10.3390/ijms19082189] [PMID: 30060458]
[24]
Aleman-Gonzalez-Duhart, D.; Tamay-Cach, F.; Alvarez-Almazan, S.; Mendieta-Wejebe, J.E. Current advances in the biochemical and physiological aspects of the treatment of type 2 diabetes mellitus with thiazolidinediones. PPAR Res., 2016, 76(, 14270), 1-11.
[25]
Dusetzina, S.B.; Higashi, A.S.; Dorsey, E.R.; Conti, R.; Huskamp, H.A.; Zhu, S.; Garfield, C.F.; Alexander, G.C. Impact of FDA drug risk communications on health care utilization and health behaviors: a systematic review. Med. Care, 2012, 50(6), 466-478.
[http://dx.doi.org/10.1097/MLR.0b013e318245a160] [PMID: 22266704]
[26]
Hickson, R.P.; Cole, A.L.; Dusetzina, S.B. Implications of Removing Rosiglitazone’s Black Box Warning and Restricted Access Program on the Uptake of Thiazolidinediones and Dipeptidyl Peptidase-4 Inhibitors Among Patients with Type 2 Diabetes. J. Manag. Care Spec. Pharm., 2019, 25(1), 72-79.
[http://dx.doi.org/10.18553/jmcp.2019.25.1.072] [PMID: 30589625]
[27]
Tucker, M.E. FDA Lifts Final Regulatory Restrictions on Rosiglitazone; Medscape, 2015.
[28]
Batool, M.; Ahmad, B.; Choi, S. A Structure-based drug discovery paradigm. Int. J. Mol. Sci., 2019, 20(11), 1-18.
[29]
Engilberge, S.; Wagner, T.; Santoni, G.; Breyton, C.; Shima, S.; Franzetti, B.; Riobé, F.; Maury, O.; Girard, E. Protein crystal structure determination with the crystallophore, a nucleating and phasing agent. J. Appl. Cryst., 2019, 52(Pt 4), 722-731.
[http://dx.doi.org/10.1107/S1600576719006381] [PMID: 31396026]
[30]
Deschamps, J.R. X-ray crystallography of chemical compounds. Life Sci., 2010, 86(15-16), 585-589.
[http://dx.doi.org/10.1016/j.lfs.2009.02.028] [PMID: 19303027]
[31]
Szymczyna, B.R.; Taurog, R.E.; Young, M.J.; Snyder, J.C.; Johnson, J.E.; Williamson, J.R. Synergy of NMR, computation, and X-ray crystallography for structural biology. Structure, 2009, 17(4), 499-507.
[http://dx.doi.org/10.1016/j.str.2009.03.001] [PMID: 19368883]
[32]
Deng, H.; Jia, Y.; Zhang, Y. Protein structure prediction. Int. J. Mod. Phys. B, 2018, 32(18), 1840009.
[http://dx.doi.org/10.1142/S021797921840009X] [PMID: 30853739]
[33]
Yu, W.; MacKerell, A.D., Jr Computer-aided drug design methods. Methods Mol. Biol., 2017, 1520, 85-106.
[http://dx.doi.org/10.1007/978-1-4939-6634-9_5] [PMID: 27873247]
[34]
Nero, T.L.; Parker, M.W.; Morton, C.J. Protein structure and computational drug discovery. Biochem. Soc. Trans., 2018, 46(5), 1367-1379.
[http://dx.doi.org/10.1042/BST20180202] [PMID: 30242117]
[35]
Valeur, E.; Narjes, F.; Ottmann, C.; Plowright, A.T. Emerging modes-of-action in drug discovery. MedChemComm, 2019, 10(9), 1550-1568.
[http://dx.doi.org/10.1039/C9MD00263D] [PMID: 31673315]
[36]
Strasser, A.; Wittmann, H.J.; Seifert, R. Binding Kinetics and Pathways of Ligands to GPCRs. Trends Pharmacol. Sci., 2017, 38(8), 717-732.
[http://dx.doi.org/10.1016/j.tips.2017.05.005] [PMID: 28645833]
[37]
Cuzzolin, A.; Sturlese, M.; Deganutti, G.; Salmaso, V.; Sabbadin, D.; Ciancetta, A.; Moro, S. Deciphering the Complexity of Ligand-Protein Recognition Pathways Using Supervised Molecular Dynamics (SuMD) Simulations. J. Chem. Inf. Model., 2016, 56(4), 687-705.
[http://dx.doi.org/10.1021/acs.jcim.5b00702] [PMID: 27019343]
[38]
Lee, Y.; Basith, S.; Choi, S. Recent Advances in Structure-Based Drug Design Targeting Class A G Protein-Coupled Receptors Utilizing Crystal Structures and Computational Simulations. J. Med. Chem., 2018, 61(1), 1-46.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01453] [PMID: 28657745]
[39]
Chou, K-C.; Watenpaugh, K.D.; Heinrikson, R.L. A model of the complex between cyclin-dependent kinase 5 and the activation domain of neuronal Cdk5 activator. Biochem. Biophys. Res. Commun., 1999, 259(2), 420-428.
[http://dx.doi.org/10.1006/bbrc.1999.0792] [PMID: 10362524]
[40]
Zhang, J.; Luan, C.H.; Chou, K.C.; Johnson, G.V. Identification of the N-terminal functional domains of Cdk5 by molecular truncation and computer modeling. Proteins, 2002, 48(3), 447-453.
[http://dx.doi.org/10.1002/prot.10173] [PMID: 12112670]
[41]
Chou, K.C.; Wei, D.Q.; Zhong, W.Z. Binding mechanism of coronavirus main proteinase with ligands and its implication to drug design against SARS. Biochem. Biophys. Res. Commun., 2003, 308(1), 148-151.
[http://dx.doi.org/10.1016/S0006-291X(03)01342-1] [PMID: 12890493]
[42]
Wang, S.Q.; Du, Q.S.; Chou, K.C. Study of drug resistance of chicken influenza A virus (H5N1) from homology-modeled 3D structures of neuraminidases. Biochem. Biophys. Res. Commun., 2007, 354(3), 634-640.
[http://dx.doi.org/10.1016/j.bbrc.2006.12.235] [PMID: 17266937]
[43]
Chou, K.C. Molecular therapeutic target for type-2 diabetes. J. Proteome Res., 2004, 3(6), 1284-1288.
[http://dx.doi.org/10.1021/pr049849v] [PMID: 15595739]
[44]
Li, X.B.; Wang, S.Q.; Xu, W.R.; Wang, R.L.; Chou, K.C. Novel inhibitor design for hemagglutinin against H1N1 influenza virus by core hopping method. PLoS One, 2011, 6(11), e28111.
[http://dx.doi.org/10.1371/journal.pone.0028111] [PMID: 22140516]
[45]
Wang, J-F.; Chou, K-C. Insights from modeling the 3D structure of New Delhi metallo-β-lactamse and its binding interactions with antibiotic drugs. PLoS One, 2011, 6(4), e18414-e18414.
[http://dx.doi.org/10.1371/journal.pone.0018414] [PMID: 21494599]
[46]
Wang, J.F.; Chou, K.C. Insights into the mutation-induced HHH syndrome from modeling human mitochondrial ornithine transporter-1. PLoS One, 2012, 7(1), e31048.
[http://dx.doi.org/10.1371/journal.pone.0031048] [PMID: 22292090]
[47]
Pielak, R.M.; Schnell, J.R.; Chou, J.J. Mechanism of drug inhibition and drug resistance of influenza A M2 channel. Proc. Natl. Acad. Sci. USA, 2009, 106(18), 7379-7384.
[http://dx.doi.org/10.1073/pnas.0902548106] [PMID: 19383794]
[48]
Aulner, N.; Danckaert, A.; Ihm, J.; Shum, D.; Shorte, S.L. Next-Generation Phenotypic Screening in Early Drug Discovery for Infectious Diseases. Trends Parasitol., 2019, 35(7), 559-570.
[http://dx.doi.org/10.1016/j.pt.2019.05.004] [PMID: 31176583]
[49]
Bueschbell, B.; Barreto, C.A.V.; Preto, A.J.; Schiedel, A.C.; Moreira, I.S. A complete assessment of dopamine receptor- ligand interactions through computational methods. Molecules, 2019, 24(7), 1-26.
[http://dx.doi.org/10.3390/molecules24071196] [PMID: 30934701]
[50]
Wright, M.B.; Bortolini, M.; Tadayyon, M.; Bopst, M. Minireview: Challenges and opportunities in development of PPAR agonists. Mol. Endocrinol., 2014, 28(11), 1756-1768.
[http://dx.doi.org/10.1210/me.2013-1427] [PMID: 25148456]
[51]
Hughes, T.S.; Chalmers, M.J.; Novick, S.; Kuruvilla, D.S.; Chang, M.R.; Kamenecka, T.M.; Rance, M.; Johnson, B.A.; Burris, T.P.; Griffin, P.R.; Kojetin, D.J. Ligand and receptor dynamics contribute to the mechanism of graded PPARγ agonism. Structure, 2012, 20(1), 139-150.
[http://dx.doi.org/10.1016/j.str.2011.10.018] [PMID: 22244763]
[52]
Gelman, L.; Feige, J.N.; Desvergne, B. Molecular basis of selective PPARgamma modulation for the treatment of Type 2 diabetes. Biochim. Biophys. Acta, 2007, 1771(8), 1094-1107.
[http://dx.doi.org/10.1016/j.bbalip.2007.03.004] [PMID: 17459763]
[53]
Pirat, C.; Farce, A.; Lebègue, N.; Renault, N.; Furman, C.; Millet, R.; Yous, S.; Speca, S.; Berthelot, P.; Desreumaux, P.; Chavatte, P. Targeting peroxisome proliferator-activated receptors (PPARs): development of modulators. J. Med. Chem., 2012, 55(9), 4027-4061.
[http://dx.doi.org/10.1021/jm101360s] [PMID: 22260081]
[54]
Rajapaksha, H.; Bhatia, H.; Wegener, K.; Petrovsky, N.; Bruning, J.B. X-ray crystal structure of rivoglitazone bound to PPARγ and PPAR subtype selectivity of TZDs. Biochim. Biophys. Acta, Gen. Subj., 2017, 1861(8), 1981-1991.
[http://dx.doi.org/10.1016/j.bbagen.2017.05.008] [PMID: 28499821]
[55]
Gampe, R.T., Jr; Montana, V.G.; Lambert, M.H.; Miller, A.B.; Bledsoe, R.K.; Milburn, M.V.; Kliewer, S.A.; Willson, T.M.; Xu, H.E. Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors. Mol. Cell, 2000, 5(3), 545-555.
[http://dx.doi.org/10.1016/S1097-2765(00)80448-7] [PMID: 10882139]
[56]
Feldman, P.L.; Lambert, M.H.; Henke, B.R. PPAR modulators and PPAR pan agonists for metabolic diseases: the next generation of drugs targeting peroxisome proliferator-activated receptors? Curr. Top. Med. Chem., 2008, 8(9), 728-749.
[http://dx.doi.org/10.2174/156802608784535084] [PMID: 18537685]
[57]
Pourcet, B.; Fruchart, J.C.; Staels, B.; Glineur, C. Selective PPAR modulators, dual and pan PPAR agonists: multimodal drugs for the treatment of type 2 diabetes and atherosclerosis. Expert Opin. Emerg. Drugs, 2006, 11(3), 379-401.
[http://dx.doi.org/10.1517/14728214.11.3.379] [PMID: 16939380]
[58]
Jones, D. Potential remains for PPAR-targeted drugs. Nat. Rev. Drug Discov., 2010, 9(9), 668-669.
[http://dx.doi.org/10.1038/nrd3271] [PMID: 20811368]
[59]
Motani, A.; Wang, Z.; Weiszmann, J.; McGee, L.R.; Lee, G.; Liu, Q.; Staunton, J.; Fang, Z.; Fuentes, H.; Lindstrom, M.; Liu, J.; Biermann, D.H.; Jaen, J.; Walker, N.P.; Learned, R.M.; Chen, J.L.; Li, Y. INT131: a selective modulator of PPAR gamma. J. Mol. Biol., 2009, 386(5), 1301-1311.
[http://dx.doi.org/10.1016/j.jmb.2009.01.025] [PMID: 19452630]
[60]
Amato, A.A.; Rajagopalan, S.; Lin, J.Z.; Carvalho, B.M.; Figueira, A.C.; Lu, J.; Ayers, S.D.; Mottin, M.; Silveira, R.L.; Souza, P.C.; Mourão, R.H.; Saad, M.J.; Togashi, M.; Simeoni, L.A.; Abdalla, D.S.; Skaf, M.S.; Polikparpov, I.; Lima, M.C.; Galdino, S.L.; Brennan, R.G.; Baxter, J.D.; Pitta, I.R.; Webb, P.; Phillips, K.J.; Neves, F.A. GQ-16, a novel peroxisome proliferator-activated receptor γ (PPARγ) ligand, promotes insulin sensitization without weight gain. J. Biol. Chem., 2012, 287(33), 28169-28179.
[http://dx.doi.org/10.1074/jbc.M111.332106] [PMID: 22584573]
[61]
Lee, M.A.; Tan, L.; Yang, H. Im, Y.G.; Im, Y.J. Structures of PPARγ complexed with lobeglitazone and pioglitazone reveal key determinants for the recognition of antidiabetic drugs. Sci. Rep., 2017, 7(1), 16837.
[http://dx.doi.org/10.1038/s41598-017-17082-x] [PMID: 29203903]
[62]
Jang, J. Y.; Bae, H.; Lee, Y. J.; Choi, Y. I.; Kim, H.- J.; Park, S. B.; Suh, S. W.; Kim, S. W.; Han, B. W. Structural Basis for the Enhanced Anti-Diabetic Efficacy of Lobeglitazone on PPARγ. Scientific Reports, 2018, 18(1), 31.
[http://dx.doi.org/10.1038/s41598-017-18274-1]
[63]
Ohashi, M.; Gamo, K.; Tanaka, Y.; Waki, M.; Beniyama, Y.; Matsuno, K.; Wada, J.; Tenta, M.; Eguchi, J.; Makishima, M.; Matsuura, N.; Oyama, T.; Miyachi, H. Structural design and synthesis of arylalkynyl amide-type peroxisome proliferator-activated receptor γ (PPARγ)-selective antagonists based on the helix12-folding inhibition hypothesis. Eur. J. Med. Chem., 2015, 90, 53-67.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.017] [PMID: 25461311]
[64]
Ohashi, M.; Gamo, K.; Oyama, T.; Miyachi, H. Peroxisome proliferator-activated receptor gamma (PPARγ) has multiple binding points that accommodate ligands in various conformations: Structurally similar PPARγ partial agonists bind to PPARγ LBD in different conformations. Bioorg. Med. Chem. Lett., 2015, 25(14), 2758-2762.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.025] [PMID: 26025876]
[65]
Shinozuka, T.; Tsukada, T.; Fujii, K.; Tokumaru, E.; Shimada, K.; Onishi, Y.; Matsui, Y.; Wakimoto, S.; Kuroha, M.; Ogata, T.; Araki, K.; Ohsumi, J.; Sawamura, R.; Watanabe, N.; Yamamoto, H.; Fujimoto, K.; Tani, Y.; Mori, M.; Tanaka, J. Discovery of DS-6930, a potent selective PPARγ modulator. Part I: Lead identification. Bioorg. Med. Chem., 2018, 26(18), 5079-5098.
[http://dx.doi.org/10.1016/j.bmc.2018.09.006] [PMID: 30241907]
[66]
Connors, R.V.; Wang, Z.; Harrison, M.; Zhang, A.; Wanska, M.; Hiscock, S.; Fox, B.; Dore, M.; Labelle, M.; Sudom, A.; Johnstone, S.; Liu, J.; Walker, N.P.; Chai, A.; Siegler, K.; Li, Y.; Coward, P. Identification of a PPARdelta agonist with partial agonistic activity on PPARgamma. Bioorg. Med. Chem. Lett., 2009, 19(13), 3550-3554.
[http://dx.doi.org/10.1016/j.bmcl.2009.04.151] [PMID: 19464171]
[67]
Ohashi, M.; Oyama, T.; Putranto, E.W.; Waku, T.; Nobusada, H.; Kataoka, K.; Matsuno, K.; Yashiro, M.; Morikawa, K.; Huh, N.H.; Miyachi, H. Design and synthesis of a series of α-benzyl phenylpropanoic acid-type peroxisome proliferator-activated receptor (PPAR) gamma partial agonists with improved aqueous solubility. Bioorg. Med. Chem., 2013, 21(8), 2319-2332.
[http://dx.doi.org/10.1016/j.bmc.2013.02.003] [PMID: 23490155]
[68]
Ahmadi, A.; Parisa Ghaderi, M.K.; Rastegar, G.; Nahri-Niknafs, B. Synthesis and blood glucose and lipid-lowering effects of benzothiazole-substituted benzenesulfonylurea derivatives. Monatsh. Chem., 2015, 146(12), 2059-2065.
[http://dx.doi.org/10.1007/s00706-015-1471-2]
[69]
Mariappan, G.; Prabhat, P.; Sutharson, L.; Banerjee, J.; Patangia, U.; Nath, S. Synthesis and antidiabetic evaluation of benzothiazole derivatives. J. Korean Chem. Soc., 2012, 56(2), 251-256.
[http://dx.doi.org/10.5012/jkcs.2012.56.2.251]
[70]
Bhutani, R.; Pathak, D.P.; Kapoor, G.; Husain, A.; Iqbal, M.A. Novel hybrids of benzothiazole-1,3,4-oxadiazole-4-thiazolidinone: Synthesis, in silico ADME study, molecular docking and in vivo anti-diabetic assessment. Bioorg. Chem., 2019, 83, 6-19.
[http://dx.doi.org/10.1016/j.bioorg.2018.10.025] [PMID: 30339863]
[71]
Murtuja, S.; Shaquiquzzaman, M.; Amir, M. Design, Synthesis, and screening of hybrid benzothiazolyl-oxadiazoles as anticonvulsant agents. Lett. Drug Des. Discov., 2018, 15(4), 398-405.
[http://dx.doi.org/10.2174/1570180814666170526154914]
[72]
Subramanyam, M.; Sreenivasulu, R.; Gundla, R.; Rao, M.V.; Rao, K.P. Synthesis, biological evaluation and docking studies of 1, 3, 4-oxadiazole fused benzothiazole derivatives for anticancer drugs. Lett. Drug Des. Discov., 2018, 15(12), 1299-1307.
[http://dx.doi.org/10.2174/1570180815666180219165119]
[73]
Akhtar, T.; Hameed, S.; Al-Masoudi, N.A.; Loddo, R.; La Colla, P. In vitro antitumor and antiviral activities of new benzothiazole and 1,3,4-oxadiazole-2-thione derivatives. Acta Pharm., 2008, 58(2), 135-149.
[http://dx.doi.org/10.2478/v10007-008-0007-2] [PMID: 18515224]
[74]
Ismail, M.A.; El Ella, D.A.A.; Abouzid, K.A.; Jaballah, M. Design, synthesis and virtual screening of certain 2-pyrazolin-5-one and pyrazolidine-3, 5-dione derivatives as potential PPARγ agonists. Int. J. Pharm. Sci. Res., 2012, 3(10), 3746-3757.
[75]
Kumar, H.; Jain, S. Synthesis and antimicrobial evaluation of 4-benzylidene-pyrazolidine-3, 5-dione derivatives. Int. J. Pharmceut. Res., 2013, 4(1), 453-457.
[76]
Moydeen, M.; Kumar, R.S.; Idhayadhulla, A.; Manilal, A. Effective synthesis of some novel pyrazolidine-3,5-dione derivatives via Mg(II) catalyzed in water medium and their anticancer and antimicrobial activities. Mol. Divers., 2019, 23(1), 35-53.
[http://dx.doi.org/10.1007/s11030-018-9850-3] [PMID: 29974311]
[77]
Suma, B.; Rochani, A.K.; Venkataramana, C.; Jays, J.; Madhavan, V. Synthesis, characterization, in vitro antibacterial, anti inflammatory evaluations of novel 4-quinolone containing pyrazolidinedione derivatives. Int. J. Chemtech Res., 2010, 2, 2156-2162.
[78]
Zhang, X. Yi-Fei, G.; Chen, T.; Yang, D.-X.; Wang, X.-X.; Jiang, B.-L.; Shao, K.-P.; Zhao, W.; Wang, C.; Wang, J.-W.; Zhang, Q.-R.; Liu, H.-M. Synthesis, in vitro and in vivo anticancer activities of novel 4-substituted 1,2-bis(4-chlorophenyl)-pyrazolidine-3,5-dione derivatives. MedChemComm, 2015, 6(10), 1781-1786.
[http://dx.doi.org/10.1039/C5MD00240K]
[79]
Tiwari, A.; Singh, A. Synthesis and antinociceptive activity of novel mannich base derivatives of some new fused 3,5-pyrazolidinedione. J. Adv. Pharm. Technol. Res., 2014, 5(1), 41-47.
[http://dx.doi.org/10.4103/2231-4040.126993] [PMID: 24696816]
[80]
Kornet, M.J.; Thorstenson, J.H.; Lubawy, W.C. Anticonvulsant activity of 1-alkyl-4-substituted 3,5-pyrazolidinediones. J. Pharm. Sci., 1974, 63(7), 1090-1093.
[http://dx.doi.org/10.1002/jps.2600630712] [PMID: 4850600]
[81]
Samala, G.; Kakan, S.S.; Nallangi, R.; Devi, P.B.; Sridevi, J.P.; Saxena, S.; Yogeeswari, P.; Sriram, D. Investigating structure activity relationship and mechanism of action of antitubercular 1-(4-chlorophenyl)-4-(4-hydroxy-3-methoxy-5-nitrobenzylidene) pyrazolidine-3,5-dione [CD59]. Int. J. Mycobacteriol., 2014, 3(2), 117-126. [CD59].
[http://dx.doi.org/10.1016/j.ijmyco.2014.02.006] [PMID: 26786333]
[82]
Cauvin, C.; Le Bourdonnec, B.; Norberg, B.; Hénichart, J-P.; Durant, F. Pyrazolidine-3,5-dione angiotensin-II receptor antagonists. Acta Crystallogr. C, 2001, 57(Pt 11), 1330-1332.
[http://dx.doi.org/10.1107/S0108270101013506] [PMID: 11706265]
[83]
Bhutani, R.; Pathak, D.P.; Kapoor, G.; Husain, A.; Kant, R.; Iqbal, M.A. Synthesis, molecular modelling studies and ADME prediction of benzothiazole clubbed oxadiazole-Mannich bases, and evaluation of their anti-diabetic activity through in vivo model. Bioorg. Chem., 2018, 77, 6-15.
[http://dx.doi.org/10.1016/j.bioorg.2017.12.037] [PMID: 29316509]
[84]
Ammazzalorso, A.; Giancristofaro, A.; D’Angelo, A.; Filippis, B.D.; Fantacuzzi, M.; Giampietro, L.; Maccallini, C.; Amoroso, R. Benzothiazole-based N-(phenylsulfonyl)amides as a novel family of PPARα antagonists. Bioorg. Med. Chem. Lett., 2011, 21(16), 4869-4872.
[http://dx.doi.org/10.1016/j.bmcl.2011.06.028] [PMID: 21742490]
[85]
Fujieda, H.; Usui, S.; Suzuki, T.; Nakagawa, H.; Ogura, M.; Makishima, M.; Miyata, N. Phenylpropanoic acid derivatives bearing a benzothiazole ring as PPARdelta-selective agonists. Bioorg. Med. Chem. Lett., 2007, 17(15), 4351-4357.
[http://dx.doi.org/10.1016/j.bmcl.2007.05.017] [PMID: 17524643]
[86]
Haroun, M.; Tratrat, C.; Tsolaki, E.; Geronikaki, A. Thiazole-Based Thiazolidinones as Potent Antimicrobial Agents. Design, Synthesis and Biological Evaluation. Comb. Chem. High Throughput Screen., 2016, 19(1), 51-57.
[http://dx.doi.org/10.2174/1386207319666151203002348] [PMID: 26632442]
[87]
Haroun, M.; Tratrat, C.; Kositsi, K.; Tsolaki, E.; Petrou, A.; Aldhubiab, B.; Attimarad, M.; Harsha, S.; Geronikaki, A.; Venugopala, K.N.; Elsewedy, H.S.; Sokovic, M.; Glamoclija, J.; Ciric, A. New benzothiazole-based thiazolidinones as potent antimicrobial agents. design, synthesis and biological evaluation. Curr. Top. Med. Chem., 2018, 18(1), 75-87.
[http://dx.doi.org/10.2174/1568026618666180206101814] [PMID: 29412109]
[88]
Fesatidou, M.; Zagaliotis, P.; Camoutsis, C.; Petrou, A.; Eleftheriou, P.; Tratrat, C.; Haroun, M.; Geronikaki, A.; Ciric, A.; Sokovic, M. 5-Adamantan thiadiazole-based thiazolidinones as antimicrobial agents. Design, synthesis, molecular docking and evaluation. Bioorg. Med. Chem., 2018, 26(16), 4664-4676.
[http://dx.doi.org/10.1016/j.bmc.2018.08.004] [PMID: 30107969]
[89]
Ismail, M.A.; Tratrat, C.; Haroun, M.G. Molecular modelling design, synthesis and cytotoxic evaluation of certain substituted 2-(3,4,5-triacetoxybenzoylamino)benzo[d]thiazole and 2-(galloylamino)benzo[d]thiazole derivatives having potential topoisomerase-I inhibitory activity. J. Enzyme Inhib. Med. Chem., 2013, 28(6), 1331-1345.
[http://dx.doi.org/10.3109/14756366.2012.716835] [PMID: 22957723]
[90]
Tratrat, C.; Haroun, M.; Xenikakis, I.; Liaras, K.; Tsolaki, E.; Eleftheriou, P.; Petrou, A.; Aldhubiab, B.; Attimarad, M.; Venugopala, K.N.; Harsha, S.; Elsewedy, H.S.; Geronikaki, A.; Soković, M. Design, synthesis, evaluation of antimicrobial activity and docking studies of new thiazole-based chalcones. Curr. Top. Med. Chem., 2019, 19(5), 356-375.
[http://dx.doi.org/10.2174/1568026619666190129121933] [PMID: 30706816]
[91]
Haroun, M. Novel hybrids of pyrazolidinedione and benzothiazole as TZD analogues. rationale design, synthesis and in vivo anti-diabetic evaluation. Med. Chem., 2019, 15(6), 624-633.
[http://dx.doi.org/10.2174/1573406415666190515093657] [PMID: 31113352]
[92]
Mariappan, G.; Saha, B.; Datta, S.; Kumar, D.; Haldar, P. Design, synthesis and antidiabetic evaluation of oxazolone derivatives. J. Chem. Sci., 2011, 123(3), 335-341.
[http://dx.doi.org/10.1007/s12039-011-0079-2]

Rights & Permissions Print Cite
Article Metrics
36
1
© 2024 Bentham Science Publishers | Privacy Policy