Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

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

Research Article

Synthesis, Characterization and Screening of Some Novel 2-Methyl-N'- [(Z)-Substituted-Phenyl ethylidene] Imidazo [1, 2-a] Pyridine-3-Carbohy drazide Derivatives as DPP-IV Inhibitors for the Treatment of Type 2 Diabetes Mellitus

Author(s): Prerana A. Chavan* and Shailaja B. Jadhav

Volume 19, Issue 2, 2022

Published on: 01 September, 2021

Page: [160 - 174] Pages: 15

DOI: 10.2174/1570180818666210901125958

Price: $65

Abstract

Background: One of the leading global metabolic diseases marked by insulin resistance and chronic hyperglycemia is type 2 diabetes mellitus (T2DM). Since the last decade, DPP-4 enzyme inhibition has proven to be a successful, safe, and well-established therapy for the treatment of T2DM.

Objective: The present work reports the synthesis, characterization, and screening of some novel 2- methyl-N'-[(Z)-substituted-phenyl ethylidene] imidazo [1, 2-a] pyridine-3-carbohydrazide derivatives as DPP-IV inhibitors for the treatment of T2DM.

Methods: The molecular docking was performed to study these derivatives' binding mode in the enzyme's allosteric site. All the synthesized compounds were subjected for DPP-IV enzyme assay and in vivo antihyperglycemic activity in STZ-induced diabetic rats.

Results: The synthesized derivatives exhibited potent antidiabetic activity as compared to the standard drug Sitagliptin. Out of sixteen compounds, A1, A4, B4, C2, C3, and D4 have shown promising antidiabetic activity against the DPP-IV enzyme. The most promising compound, C2, showed a percentage inhibition of 72.02±0.27 at 50 μM concentration. On the 21st-day, compound C2 showed a significant reduction in serum blood glucose level, i.e., 156.16±4.87 mg/dL, then diabetic control, which was 280.00±13.29 mg/dL whereas, standard Sitagliptin showed 133.50±11.80 mg/dL. In the in vivo antihyperglycemic activity, the compounds have exhibited good hypoglycemic potential in fasting blood glucose in the T2DM animal model. All the docked molecules have exhibited perfect binding affinity towards the active pocket of the enzyme. The synthesized derivatives were screened through Lipinski's rule of five for better optimization, and fortunately, none of them violated the rule.

Conclusion: The above results indicate that compound C2 is a relatively active and selective hit molecule that can be structurally modified to enhance the DPP-IV inhibitor's potency and overall pharmacological profile. From the present work, it has been concluded that substituted pyridine-3-carbohydrazide derivatives possess excellent DPP-IV inhibitory potential and can be better optimized further by generating more in vivo, in vitro models.

Keywords: DPP-IV inhibitors, Type 2 diabetes mellitus, T2DM, pyridine-3-carbohydrazides, enzyme assay, molecular docking.

Graphical Abstract

[1]
Olokoba, A.B.; Obateru, O.A.; Olokoba, L.B. Type 2 diabetes mellitus: A review of current trends. Oman Med. J., 2012, 27(4), 269-273.
[http://dx.doi.org/10.5001/omj.2012.68] [PMID: 23071876]
[2]
Patel, B.D.; Bhadada, S.V.; Ghate, M.D. Design, synthesis and anti-diabetic activity of triazolotriazine derivatives as dipeptidyl peptidase-4 (DPP-4) inhibitors. Bioorg. Chem., 2017, 72, 345-358.
[http://dx.doi.org/10.1016/j.bioorg.2017.03.004] [PMID: 28302310]
[3]
Centers for disease control and prevention. national diabetes statistics report: Estimates of diabetes and its burden in the united states. US Dep. Heal. Hum. Serv., 2014.
[4]
Li, N.; Wang, L.J.; Jiang, B.; Guo, S.J.; Li, X.Q.; Chen, X.C.; Luo, J.; Li, C.; Wang, Y.; Shi, D.Y. Design, synthesis and biological evaluation of novel pyrimidinedione derivatives as DPP-4 inhibitors. Bioorg. Med. Chem. Lett., 2018, 28(12), 2131-2135.
[http://dx.doi.org/10.1016/j.bmcl.2018.05.022] [PMID: 29773502]
[5]
Wang, J.; Feng, Y.; Ji, X.; Deng, G.; Leng, Y.; Liu, H. Synthesis and biological evaluation of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2-carbonitrile derivatives as dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes. Bioorg. Med. Chem., 2013, 21(23), 7418-7429.
[http://dx.doi.org/10.1016/j.bmc.2013.09.048] [PMID: 24153396]
[6]
Sharma, M.; Gupta, M.; Singh, D.; Kumar, M.; Kaur, P. Synthesis, evaluation and molecular docking of thiazolopyrimidine derivatives as dipeptidyl peptidase IV inhibitors. Chem. Biol. Drug Des., 2012, 80(6), 918-928.
[http://dx.doi.org/10.1111/cbdd.12041] [PMID: 22943413]
[7]
Gallwitz, B. Clinical Use of DPP-4 Inhibitors. Front. Endocrinol. (Lausanne), 2019, 10, 389.
[http://dx.doi.org/10.3389/fendo.2019.00389] [PMID: 31275246]
[8]
Tsai, T.Y.; Hsu, T.; Chen, C.T.; Cheng, J.H.; Chiou, M.C.; Huang, C.H.; Tseng, Y.J.; Yeh, T.K.; Huang, C.Y.; Yeh, K.C.; Huang, Y.W.; Wu, S.H.; Wang, M.H.; Chen, X.; Chao, Y.S.; Jiaang, W.T. Rational design and synthesis of potent and long-lasting glutamic acid-based dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(7), 1908-1912.
[http://dx.doi.org/10.1016/j.bmcl.2009.02.061] [PMID: 19269819]
[9]
Narsimha, S.; Battula, K.S.; Ravinder, M.; Reddy, Y.N.; Nagavelli, V.R. Design, synthesis and biological evaluation of novel 1,2,3-triazole-based xanthine derivatives as DPP-4 inhibitors. J. Chem. Sci., 2020, 132(1)
[http://dx.doi.org/10.1007/s12039-020-1760-0]
[10]
Abd El-Karim, S.S.; Anwar, M.M.; Syam, Y.M.; Nael, M.A.; Ali, H.F.; Motaleb, M.A. Rational design and synthesis of new tetralin-sulfonamide derivatives as potent anti-diabetics and DPP-4 inhibitors: 2D & 3D QSAR, in vivo radiolabeling and bio distribution studies. Bioorg. Chem., 2018, 81, 481-493.
[http://dx.doi.org/10.1016/j.bioorg.2018.09.021] [PMID: 30243239]
[11]
Han, B.; Liu, J.L.; Huan, Y.; Li, P.; Wu, Q.; Lin, Z.Y.; Shen, Z.F.; Yin, D.L.; Huang, H.H. Design, Synthesis and Primary Activity of Thiomorpholine Derivatives as DPP-IV Inhibitors. Chin. Chem. Lett., 2012, 23(3), 297-300.
[http://dx.doi.org/10.1016/j.cclet.2011.12.007]
[12]
Pereira, A.L.E.; Dos Santos, G.B.; Franco, M.S.F.; Federico, L.B.; da Silva, C.H.T.P.; Santos, C.B.R. Molecular modeling and statistical analysis in the design of derivatives of human dipeptidyl peptidase IV. J. Biomol. Struct. Dyn., 2018, 36(2), 318-334.
[http://dx.doi.org/10.1080/07391102.2016.1277163] [PMID: 28027711]
[13]
Scheen, A.J. Safety of dipeptidyl peptidase-4 inhibitors for treating type 2 diabetes. Expert Opin. Drug Saf., 2015, 14(4), 505-524.
[http://dx.doi.org/10.1517/14740338.2015.1006625] [PMID: 25630605]
[14]
Tella, S.H.; Rendell, M.S. DPP-4 inhibitors: Focus on safety. Expert Opin. Drug Saf., 2015, 14(1), 127-140.
[http://dx.doi.org/10.1517/14740338.2015.977863] [PMID: 25488788]
[15]
Gupta, R.; Walunj, S.S.; Tokala, R.K.; Parsa, K.V.; Singh, S.K.; Pal, M. Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr. Drug Targets, 2009, 10(1), 71-87.
[http://dx.doi.org/10.2174/138945009787122860] [PMID: 19149538]
[16]
Lacroix, I.M.E.; Li-Chan, E.C.Y. Food-derived dipeptidyl-peptidase IV inhibitors as a potential approach for glycemic regulation - current knowledge and future research considerations. Trends Food Sci. Technol., 2016, •••, 1-16.
[http://dx.doi.org/10.1016/j.tifs.2016.05.008]
[17]
Smelcerovic, A.; Miljkovic, F.; Kolarevic, A.; Lazarevic, J.; Djordjevic, A.; Kocic, G.; Anderluh, M. An overview of recent dipeptidyl peptidase-IV inhibitors: Linking their structure and physico-chemical properties with sar, pharmacokinetics and toxicity. Curr. Top. Med. Chem., 2015, 15(23), 2342-2372.
[http://dx.doi.org/10.2174/1568026615666150619142731] [PMID: 26088350]
[18]
Salvatore, T.; Carbonara, O.; Cozzolino, D.; Torella, R.; Sasso, F.C. Adapting the GLP-1-signaling system to the treatment of type 2 diabetes. Curr. Diabetes Rev., 2007, 3(1), 15-23.
[http://dx.doi.org/10.2174/157339907779802076] [PMID: 18220652]
[19]
Kushwaha, R.N.; Haq, W.; Katti, S.B. Sixteen-years of clinically relevant dipeptidyl peptidase-IV (DPP-IV) inhibitors for treatment of type-2 diabetes: A perspective. Curr. Med. Chem., 2014, 21(35), 4013-4045.
[http://dx.doi.org/10.2174/0929867321666140915143309] [PMID: 25245373]
[20]
Liu, Y.; Hu, Y.; Liu, T. Recent advances in non-peptidomimetic dipeptidyl peptidase 4 inhibitors: Medicinal chemistry and preclinical aspects. Curr. Med. Chem., 2012, 19(23), 3982-3999.
[http://dx.doi.org/10.2174/092986712802002491] [PMID: 22709010]
[21]
Salvo, F.; Moore, N.; Arnaud, M.; Robinson, P.; Raschi, E.; De Ponti, F.; Bégaud, B.; Pariente, A. Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: Systematic review and meta-analysis. BMJ, 2016, 353, i2231.
[http://dx.doi.org/10.1136/bmj.i2231] [PMID: 27142267]
[22]
Liu, M.; Sun, X.; Zhao, X. Investigating the contributions of residues to dipeptidyl peptidase-IV inhibitor binding by molecular dynamics simulation. Lett. Drug Des. Discov., 2014, 11(7), 886-893.
[http://dx.doi.org/10.2174/1570180811666140226235522]
[23]
Kumar Verma, S.; Kant Sharma, S.; Thareja, S. Docking study of novel pyrrolidine derivatives as potential dipeptidyl peptidase-IV (DPP-IV) inhibitors. Lett. Drug Des. Discov., 2015, 12(4), 284-291.
[http://dx.doi.org/10.2174/1570180811666141016000752]
[24]
Amuthalakshmi, S.; Anton Smith, A.; Manavalan, R. Modeling assisted in silico design of ligand molecule for DPP IV in type II Diabetes mellitus. Lett. Drug Des. Discov., 2012, 9(8), 764-766.
[http://dx.doi.org/10.2174/157018012802652930]
[25]
Gupta, S.; Chaudhary, K.; Raj, U.; Mishra, N. Computational Identification of Inhibitors Against DPP-IV for Checking Type-2 Diabetes. Lett. Drug Des. Discov., 2016, 14(1), 66-73.
[http://dx.doi.org/10.2174/1570180813666160720121718]
[26]
Mattei, P.; Boehringer, M.; Di Giorgio, P.; Fischer, H.; Hennig, M.; Huwyler, J.; Koçer, B.; Kuhn, B.; Loeffler, B.M.; Macdonald, A.; Narquizian, R.; Rauber, E.; Sebokova, E.; Sprecher, U. Discovery of carmegliptin: A potent and long-acting dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Bioorg. Med. Chem. Lett., 2010, 20(3), 1109-1113.
[http://dx.doi.org/10.1016/j.bmcl.2009.12.024] [PMID: 20031405]
[27]
Said, S.; Nwosu, A.C.; Mukherjee, D.; Hernandez, G.T. Alogliptin; a review of a new dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of type 2 diabetes mellitus. Cardiovasc. Hematol. Disord. Drug Targets, 2014, 14(1), 64-70.
[http://dx.doi.org/10.2174/1871529X14666140701095849] [PMID: 24993124]
[28]
Hildebrandt, M.; Reutter, W.; Arck, P.; Rose, M.; Klapp, B.F. A guardian angel: The involvement of dipeptidyl peptidase IV in psychoneuroendocrine function, nutrition and immune defence. Clin. Sci. (Lond.), 2000, 99(2), 93-104.
[http://dx.doi.org/10.1042/CS19990368] [PMID: 10918042]
[29]
Kirby, M.; Yu, D.M.T.; O’Connor, S.; Gorrell, M.D. Inhibitor selectivity in the clinical application of dipeptidyl peptidase-4 inhibition. Clin. Sci. (Lond.), 2009, 118(1), 31-41.
[http://dx.doi.org/10.1042/CS20090047] [PMID: 19780719]
[30]
Pratley, R.E.; Salsali, A. Inhibition of DPP-4: A new therapeutic approach for the treatment of type 2 diabetes. Curr. Med. Res. Opin., 2007, 23(4), 919-931.
[http://dx.doi.org/10.1185/030079906X162746] [PMID: 17407649]
[31]
El-Kaissi, S.; Sherbeeni, S. Pharmacological management of type 2 diabetes mellitus: An update. Curr. Diabetes Rev., 2011, 7(6), 392-405.
[http://dx.doi.org/10.2174/157339911797579160] [PMID: 21846326]
[32]
Liang, G.B.; Qian, X.; Biftu, T.; Singh, S.; Gao, Y.D.; Scapin, G.; Patel, S.; Leiting, B.; Patel, R.; Wu, J.; Zhang, X.; Thornberry, N.A.; Weber, A.E. Discovery of new binding elements in DPP-4 inhibition and their applications in novel DPP-4 inhibitor design. Bioorg. Med. Chem. Lett., 2008, 18(13), 3706-3710.
[http://dx.doi.org/10.1016/j.bmcl.2008.05.061] [PMID: 18524582]
[33]
Wallace, M.B.; Feng, J.; Zhang, Z.; Skene, R.J.; Shi, L.; Caster, C.L.; Kassel, D.B.; Xu, R.; Gwaltney, S.L. II Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(7), 2362-2367.
[http://dx.doi.org/10.1016/j.bmcl.2008.02.071] [PMID: 18346892]
[34]
Wu, W.L.; Hao, J.; Domalski, M.; Burnett, D.A.; Pissarnitski, D.; Zhao, Z.; Stamford, A.; Scapin, G.; Gao, Y.D.; Soriano, A.; Kelly, T.M.; Yao, Z.; Powles, M.A.; Chen, S.; Mei, H.; Hwa, J. Discovery of novel tricyclic heterocycles as potent and selective DPP-4 inhibitors for the treatment of type 2 diabetes. ACS Med. Chem. Lett., 2016, 7(5), 498-501.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00027] [PMID: 27190600]
[35]
Kaur, J.; Singla, R.; Jaitak, V. In Silico study of flavonoids as DPP-4 and α-glucosidase inhibitors. Lett. Drug Des. Discov., 2017, 14.
[http://dx.doi.org/10.2174/1570180814666170915162232]
[36]
McKeage, K. Trelagliptin: First Global Approval. Drugs, 2015, 75(10), 1161-1164.
[http://dx.doi.org/10.1007/s40265-015-0431-9] [PMID: 26115728]
[37]
Burness, C.B. Omarigliptin: First global approval. Drugs, 2015, 75(16), 1947-1952.
[http://dx.doi.org/10.1007/s40265-015-0493-8] [PMID: 26507988]
[38]
Misra, M.; Pandey, S.K.; Pandey, V.P.; Pandey, J.; Tripathi, R.; Tripathi, R.P. Organocatalyzed highly atom economic one pot synthesis of tetrahydropyridines as antimalarials. Bioorg. Med. Chem., 2009, 17(2), 625-633.
[http://dx.doi.org/10.1016/j.bmc.2008.11.062] [PMID: 19095455]
[39]
Nassiri, M. Simple, one-pot, and three-component coupling reactions of azaarenes (phenanthridine, isoquinoline, and quinoline), with acetylenic esters involving methyl propiolate or ethyl propiolate in the presence of NH-heterocyclic or 1,3-dicarbonyl compounds. Synth. Commun., 2013, 43(2), 157-168.
[http://dx.doi.org/10.1080/00397911.2011.589559]
[40]
Sonawane, R.P. Green Synthesis of Pyrimidine Derivative. Int. Lett. Chem. Phys. Astron., 2013, 21, 64-68.
[http://dx.doi.org/10.18052/www.scipress.com/ILCPA.21.64]
[41]
Samala, G.; Nallangi, R.; Devi, P.B.; Saxena, S.; Yadav, R.; Sridevi, J.P.; Yogeeswari, P.; Sriram, D. Identification and development of 2-methylimidazo[1,2-a]pyridine-3-carboxamides as Mycobacterium tuberculosis pantothenate synthetase inhibitors. Bioorg. Med. Chem., 2014, 22(15), 4223-4232.
[http://dx.doi.org/10.1016/j.bmc.2014.05.038] [PMID: 24953948]
[42]
Anilkumar, N.C.; Sundaram, M.S.; Mohan, C.D.; Rangappa, S.; Bulusu, K.C.; Fuchs, J.E.; Girish, K.S.; Bender, A. Basappa; Rangappa, K.S. A One pot synthesis of novel bioactive tri-substitute-condensed-imidazopyridines that targets snake venom phospholipase A2. PLoS One, 2015, 10(7), e0131896.
[http://dx.doi.org/10.1371/journal.pone.0131896] [PMID: 26196520]
[43]
Shinde, M.H.; Kshirsagar, U.A. One pot synthesis of substituted imidazopyridines and thiazoles from styrenes in water assisted by NBS. Green Chem., 2016, 18(6), 1455-1458.
[http://dx.doi.org/10.1039/C5GC02771C]
[44]
Iv, D. Antidiabetic activity of the selected plants by in Vitro models; Polyphenols and Diabetes, 2001, pp. 54-70.
[45]
Todd, M.J.; Gomez, J. Enzyme kinetics determined using calorimetry: A general assay for enzyme activity? Anal. Biochem., 2001, 296(2), 179-187.
[http://dx.doi.org/10.1006/abio.2001.5218] [PMID: 11554713]
[46]
Davis, J.A.; Singh, S.; Sethi, S.; Roy, S.; Mittra, S.; Rayasam, G.; Bansal, V.; Sattigeri, J.; Ray, A. Nature of action of Sitagliptin, the dipeptidyl peptidase-IV inhibitor in diabetic animals. Indian J. Pharmacol., 2010, 42(4), 229-233.
[http://dx.doi.org/10.4103/0253-7613.68425] [PMID: 20927248]
[47]
Ward, R.A.; Perkins, T.D.J.; Stafford, J. Structure-based virtual screening for low molecular weight chemical starting points for dipeptidyl peptidase IV inhibitors. J. Med. Chem., 2005, 48(22), 6991-6996.
[http://dx.doi.org/10.1021/jm0505866] [PMID: 16250657]
[48]
Zhu, Y.; Xia, S.; Zhu, M.; Yi, W.; Cheng, J.; Song, G.; Li, Z.; Lu, P. Synthesis, biological assay in vitro and molecular docking studies of new imidazopyrazinone derivatives as potential dipeptidyl peptidase IV inhibitors. Eur. J. Med. Chem., 2010, 45(11), 4953-4962.
[http://dx.doi.org/10.1016/j.ejmech.2010.08.002] [PMID: 20800322]
[49]
Caron, J.; Domenger, D.; Dhulster, P.; Ravallec, R.; Cudennec, B. Using Caco-2 cells as novel identification tool for food-derived DPP-IV inhibitors. Food Res. Int., 2017, 92, 113-118.
[http://dx.doi.org/10.1016/j.foodres.2017.01.002] [PMID: 28290288]
[50]
Walum, E. Acute oral toxicity. Environ. Health Perspect., 1998, 106(Suppl. 2), 497-503.
[http://dx.doi.org/10.1289/ehp.98106497] [PMID: 9599698]
[51]
Pant, J.; Deshpande, S.B. Acute toxicity of bisphenol A in rats. Indian J. Exp. Biol., 2012, 50(6), 425-429.
[PMID: 22734254]
[52]
Avalakki, A.S.; Jadhav, S.B.; Bandawane, D.D.; Bhalekar, P.A. Synthesis and antidiabetic evaluation of some novel compounds. Indian J. Chem. Sect. B, 2019, 58(07), 849-854.https://doi.org/http://nopr.niscair.res.in/bitstream/123456789/49105/1/IJCB%2058B%287%29%20849-854.pdf
[53]
Wilhelm, K-P.; Zhai, H.; Maibach, H.I.; Wilhelm, K-P.; Maibach, H.I. OECD guidelines for testing of chemicals. In: Dermatotoxicology; , 2012; pp. 497-499.
[54]
Maibach, H.; Wilhelm, K-P. OECD guidelines for testing of chemicals. In: Dermatotoxicology, Seventh Edition; , 2007; pp. 303-305.
[http://dx.doi.org/10.1201/9781420009774.ch33]
[55]
Nagata, M.; Suzuki, W.; Iizuka, S.; Tabuchi, M.; Maruyama, H.; Takeda, S.; Aburada, M.; Miyamoto, K. Type 2 diabetes mellitus in obese mouse model induced by monosodium glutamate. Exp. Anim., 2006, 55(2), 109-115.
[http://dx.doi.org/10.1538/expanim.55.109] [PMID: 16651693]
[56]
Zhang, M.; Lv, X.Y.; Li, J.; Xu, Z.G.; Chen, L. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp. Diabetes Res., 2008, 2008, 704045.
[http://dx.doi.org/10.1155/2008/704045] [PMID: 19132099]
[57]
Furman, B. L. Streptozotocin-Induced Diabetic Models in Mice and Rats. Curr. Protoc. Pharmacol., 2015, 70(1), 5.47.1-5.47.20.
[58]
Arulmozhi, D.K.; Veeranjaneyulu, A.; Bodhankar, S.L. Neonatal streptozotocin-induced rat model of type 2 Diabetes mellitus: A glance. Indian J. Pharmacol., 2004, 36(4), 217-221.
[59]
Cassano, V.; Leo, A.; Tallarico, M.; Nesci, V.; Cimellaro, A.; Fiorentino, T.V.; Citraro, R.; Hribal, M.L.; De Sarro, G.; Perticone, F.; Sesti, G.; Russo, E.; Sciacqua, A. Metabolic and cognitive effects of ranolazine in type 2 Diabetes mellitus: Data from an in vivo model. Nutrients, 2020, 12(2), E382.
[http://dx.doi.org/10.3390/nu12020382] [PMID: 32023991]
[60]
Al-Awar, A.; Kupai, K.; Veszelka, M.; Szűcs, G.; Attieh, Z.; Murlasits, Z.; Török, S.; Pósa, A.; Varga, C. Experimental Diabetes mellitus in different animal models. J. Diabetes Res., 2016, 2016, 9051426.
[http://dx.doi.org/10.1155/2016/9051426] [PMID: 27595114]
[61]
Okamoto, T.; Kanemoto, N.; Ohbuchi, Y.; Okano, M.; Fukui, H.; Sudo, T. Characterization of STZ-induced type 2 diabetes in zucker fatty rats. Exp. Anim., 2008, 57(4), 335-345.
[http://dx.doi.org/10.1538/expanim.57.335] [PMID: 18633156]
[62]
Dallakyan, S.; Olson, A.J. Small-molecule library screening by docking with PyRx. Methods Mol. Biol., 2015, 1263(1263), 243-250.
[http://dx.doi.org/10.1007/978-1-4939-2269-7_19] [PMID: 25618350]
[63]
Rappé, A.K.; Casewit, C.J.; Colwell, K.S.; Goddard, W.A.; Skiff, W.M. UFF, A full periodic table force field for molecular mechanics and molecular dynamics simulations. J. Am. Chem. Soc., 1992, 114(25), 10024-10035.
[http://dx.doi.org/10.1021/ja00051a040]
[64]
Systèmes, D. Dassault Systèmes BIOVIA; Discovery studio modeling environment, 2017.
[65]
Chaudhari, R.N.; Khan, S.L.; Chaudhary, R.S.; Jain, S.P.; Siddiqui, F.A. B-sitosterol: Isolation from muntingia calabura linn bark extract, structural elucidation and molecular docking studies as potential inhibitor of SARS-CoV-2 Mpro (COVID-19). Asian J. Pharm. Clin. Res., 2020, 13(5), 204-209.
[http://dx.doi.org/10.22159/ajpcr.2020.v13i5.37909]
[66]
Khan, S.L.; Siddiqui, F.A.; Jain, S.P.; Sonwane, G.M. Discovery of potential inhibitors of SARS-CoV-2 (COVID-19) main protease (Mpro) from nigella sativa (Black Seed) by molecular docking study; Coronaviruses, 2020, p. 01.
[http://dx.doi.org/10.2174/2666796701999200921094103]
[67]
Khan, S.L.; Siddiui, F.A. Beta-sitosterol: As immunostimulant, antioxidant and inhibitor of SARS-CoV-2 spike glycoproteiN. Arch. Pharmacol. Ther., 2020, 2(1)
[http://dx.doi.org/10.33696/pharmacol.2.014]
[68]
Khan, S.L.; Siddiqui, F.A.; Shaikh, M.S.; Nema, N.V.; Shaikh, A.A. Discovery of potential inhibitors of the receptor-binding domain (RBD) of pandemic disease-causing SARS-CoV-2 spike glycoprotein from triphala through molecular docking; Curr. Chinese Chem, 2021, 01, .
[http://dx.doi.org/10.2174/2666001601666210322121802]
[69]
Baell, J.; Congreve, M.; Leeson, P.; Abad-Zapatero, C. Ask the experts: Past, present and future of the rule of five. Future Med. Chem., 2013, 5(7), 745-752.
[http://dx.doi.org/10.4155/fmc.13.61] [PMID: 23651089]
[70]
Giménez, B.G.; Santos, M.S.; Ferrarini, M.; Fernandes, J.P. Evaluation of blockbuster drugs under the rule-of-five. Pharmazie, 2010, 65(2), 148-152.
[http://dx.doi.org/10.1691/ph.2010.9733] [PMID: 20225662]
[71]
Walters, W.P. Going further than Lipinski’s rule in drug design. Expert Opin. Drug Discov., 2012, 7(2), 99-107.
[http://dx.doi.org/10.1517/17460441.2012.648612] [PMID: 22468912]
[72]
Nendza, M.; Müller, M. Screening for low aquatic bioaccumulation. 1. Lipinski’s ‘Rule of 5’ and molecular size. SAR QSAR Environ. Res., 2010, 21(5-6), 495-512.
[http://dx.doi.org/10.1080/1062936X.2010.502295] [PMID: 20818584]
[73]
Li, Q.; Zhou, M.; Han, L.; Cao, Q.; Wang, X.; Zhao, L.; Zhou, J.; Zhang, H. Design, synthesis and biological evaluation of imidazo[1,2-a]pyridine derivatives as novel DPP-4 inhibitors. Chem. Biol. Drug Des., 2015, 86(4), 849-856.
[http://dx.doi.org/10.1111/cbdd.12560] [PMID: 25787859]
[74]
Kaczanowska, K.; Wiesmüller, K.H.; Schaffner, A.P. Design, synthesis, and in vitro evaluation of novel aminomethyl-pyridines as DPP-4 inhibitors. ACS Med. Chem. Lett., 2010, 1(9), 530-535.
[http://dx.doi.org/10.1021/ml100200c] [PMID: 24900243]

© 2024 Bentham Science Publishers | Privacy Policy