Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

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

Research Article

Synthesis, In vitro α-Glucosidase Inhibitory Potential and Molecular Docking Studies of 2-Amino-1,3,4-Oxadiazole Derivatives

Author(s): Hayat Ullah, Fazal Rahim, Muhammad Taha*, Raffaqat Hussain, Abdul Wadood, Mohsan Nawaz, Zainul Wahab, Kanwal and Khalid M. Khan

Volume 16, Issue 6, 2020

Page: [724 - 734] Pages: 11

DOI: 10.2174/1573406415666190612150447

Price: $65

Abstract

Background: In the recent past, we have synthesized and reported different derivatives of oxadiazoles as potential α-glucosidase inhibitors, keeping in mind, the pharmacological aspects of oxadiazole moiety and in continuation of our ongoing research on the chemistry and bioactivity of new heterocyclic compounds.

Methods: 1,3,4-Oxadiazole derivatives (1-14) have been synthesized and characterized by different spectroscopic techniques such as 1H-, 13C-NMR and HREI-MS.

Results: The synthetic derivatives were screened for α-glucosidase inhibitory potential. All compounds exhibited good inhibitory activity with IC50 values ranging between 0.80 ± 0.1 to 45.1 ± 1.7 μM in comparison with the standard acarbose having IC50 value 38.45 ± 0.80 μM.

Conclusion: Thirteen compounds 1-6 and 8-14 showed potential inhibitory activity as compared to the standard acarbose having IC50 value 38.45 ± 0.80 μM, however, only one compound 7 (IC50 = 45.1 ± 1.7 μM) was found to be less active. Compound 14 (IC50 = 0.80 ± 0.1 μM) showed promising inhibitory activity among all synthetic derivatives. Molecular docking studies were also conducted for the active compounds to understand the ligand-enzyme binding interactions.

Keywords: Synthesis, 1, 3, 4-oxadiazole, α-glucosidase, in viro, SAR, molecular docking study.

Graphical Abstract
[1]
van de Laar, F.A. α-glucosidase inhibitors in the early treatment of type 2 diabetes. Vasc. Health Risk Manag., 2008, 4(6), 1189-1195.
[http://dx.doi.org/10.2147/VHRM.S3119] [PMID: 19337532]
[2]
Joshi, S.R.; Standl, E.; Tong, N.; Shah, P.; Kalra, S.; Rathod, R. Therapeutic potential of α-glucosidase inhibitors in type 2 diabetes mellitus: an evidence-based review. Expert Opin. Pharmacother., 2015, 16(13), 1959-1981.
[http://dx.doi.org/10.1517/14656566.2015.1070827] [PMID: 26255950]
[3]
Pili, R.; Chang, J.; Partis, R.A.; Mueller, R.A.; Chrest, F.J.; Passaniti, A. The α-glucosidase I inhibitor castanospermine alters endothelial cell glycosylation, prevents angiogenesis, and inhibits tumor growth. Cancer Res., 1995, 55(13), 2920-2926.
[PMID: 7540952]
[4]
Mehta, A.; Zitzmann, N.; Rudd, P.M.; Block, T.M.; Dwek, R.A. α-glucosidase inhibitors as potential broad based anti-viral agents. FEBS Lett., 1998, 430(1-2), 17-22.
[http://dx.doi.org/10.1016/S0014-5793(98)00525-0] [PMID: 9678587]
[5]
Zitzmann, N.; Mehta, A.S.; Carrouée, S.; Butters, T.D.; Platt, F.M.; McCauley, J.; Blumberg, B.S.; Dwek, R.A.; Block, T.M. Imino sugars inhibit the formation and secretion of bovine viral diarrhea virus, a pestivirus model of hepatitis C virus: implications for the development of broad spectrum anti-hepatitis virus agents. Proc. Natl. Acad. Sci. USA, 1999, 96(21), 11878-11882.
[http://dx.doi.org/10.1073/pnas.96.21.11878] [PMID: 10518544]
[6]
Dabhi, A.S.; Bhatt, N.R.; Shah, M.J. Voglibose: an align="center" glucosidase inhibitor. J. Clin. Diagn. Res., 2013, 7(12), 3023-3027.
[PMID: 24551718]
[7]
(a)Borg, S.; Estenne-Bouhtou, G.; Luthman, K.; Csoeregh, I.; Hesselink, W.; Hacksell, U. Synthesis of 1,2,4-oxadiazole-, 1,3,4-oxadiazole-, and 1,2,4-triazole-derived dipeptidomimetics. J. Org. Chem., 1995, 60, 3112.
(b)Bala, S.; Kamboj, S.; Kajal, A.; Saini, V.; Prasad, D.N. 1,3,4-oxadiazole derivatives: synthesis, characterization, antimicrobial potential, and computational studies. Bio. Med. Res. Int., 2014, 2014, 172791.
[8]
Blouin, M.; Grimm, E.L.; Gareau, Y.; Gagnon, M.; Juteau, H.; Laliberte, S.; Mackay, B.; Friesen, R. 2006.
[9]
Zou, X.J.; Lai, L.H.; Jin, G.Y.; Zhang, Z.X. Synthesis, fungicidal activity, and 3D-QSAR of pyridazinone-substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles. J. Agric. Food Chem., 2002, 50(13), 3757-3760.
[http://dx.doi.org/10.1021/jf0201677] [PMID: 12059155]
[10]
Nofal, Z.M.; Fahmy, H.H.; Mohamed, H.S. Synthesis and antimicrobial activity of new substituted anilinobenzimidazoles. Arch. Pharm. Res., 2002, 25(3), 250-257.
[http://dx.doi.org/10.1007/BF02976622] [PMID: 12135093]
[11]
Ouyang, X.; Piatnitski, E.L.; Pattaropong, V.; Chen, X.; He, H.Y.; Kiselyov, A.S.; Velankar, A.; Kawakami, J.; Labelle, M.; Smith, L.I.I.; Lohman, J.; Lee, S.P.; Malikzay, A.; Fleming, J.; Gerlak, J.; Wang, Y.; Rosler, R.L.; Zhou, K.; Mitelman, S.; Camara, M.; Surguladze, D.; Doody, J.F.; Tuma, M.C. Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines. Bioorg. Med. Chem. Lett., 2006, 16(5), 1191-1196.
[http://dx.doi.org/10.1016/j.bmcl.2005.11.094] [PMID: 16377187]
[12]
Küçükgüzel, S.G.; Küçükgüzel, I.; Tatar, E.; Rollas, S.; Sahin, F.; Güllüce, M.; De Clercq, E.; Kabasakal, L. Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents. Eur. J. Med. Chem., 2007, 42(7), 893-901.
[http://dx.doi.org/10.1016/j.ejmech.2006.12.038] [PMID: 17418454]
[13]
Chaudhary, S.K.; Kumar, S.; Parmar, S.S.; Chaudhary, M. Mild and convenient one-pot synthesis of 2-amino-1,3,4-oxadiazoles promoted by trimethylsilyl isothiocyanate (TMSNCS). J. Pharm. Sci., 1978, 67, 7684-7687.
[14]
Handlon, A.L.; Akwabi-Ameyaw, A.; Brown, K.; De Anda, F.; Drewry, D.; Li, G.; Linn, J.A.; Milliken, N.O.; Ramanjulu, J. Abstracts of Papers 226th ACS National Meeting, 2003.
[15]
Biwersi, C.M.; Warmus, J.S.; Zhang, L.Y.; Barrett, S.D.; Kaufman, M.D.; Plummer, M.S.; Reed, J. E. WO 2004056789 , 2004.
[16]
Kiselyov, A.S.; Semenova, M.; Semenov, V.V.; Piatnitski, E.; Ouyang, S. Hetaryl imidazoles: a novel dual inhibitors of VEGF receptors I and II. Bioorg. Med. Chem. Lett., 2006, 16(5), 1440-1444.
[http://dx.doi.org/10.1016/j.bmcl.2005.11.033] [PMID: 16321531]
[17]
Ishikawa, H.; Elliott, G.I.; Velcicky, J.; Choi, Y.; Boger, D.L. Total synthesis of (-)- and ent-(+)-vindoline and related alkaloids. J. Am. Chem. Soc., 2006, 128(32), 10596-10612.
[http://dx.doi.org/10.1021/ja061256t] [PMID: 16895428]
[18]
McDonald, C.M.; Campbell, C.; Torricelli, R.E.; Finkel, R.S.; Flanigan, K.M.; Goemans, N.; Heydemann, P.; Kaminska, A.; Kirschner, J.; Muntoni, F.; Osorio, A.N.; Schara, U.; Sejersen, T.; Shieh, P.B.; Sweeney, H.L.; Topaloglu, H.; Tulinius, M.; Vilchez, J.J.; Voit, T.; Wong, B.; Elfring, G.; Kroger, H.; Luo, X.; McIntosh, J.; Ong, T.; Riebling, P.; Souza, M.; Spiegel, R.J.; Peltz, S.W.; Mercuri, E. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2017, 390(10101), 1489-1498.
[http://dx.doi.org/10.1016/S0140-6736(17)31611-2] [PMID: 28728956]
[19]
Ilangovan, A.; Saravanakumar, S.; Umesh, S. T3P as an efficient cyclodehydration reagent for the one-pot synthesis of 2-amino-1,3,4-oxadiazoles. J. Chem. Sci., 2015, 127, 797-801.
[http://dx.doi.org/10.1007/s12039-015-0834-x]
[20]
Pappachen, L.K.; James, S.; Shalumol, A.; Unnikrishnan, A.; Sreedhar, R. Synthesis of Oxadiazole derivatives: An overview. Int. J. Pharm. Sci. Rev. Res., 2016, 41, 142-153.
[21]
(a)Rahim, F.; Ullah, K.; Ullah, H.; Wadood, A.; Taha, M.; Ur Rehman, A.; Uddin, I.; Ashraf, M.; Shaukat, A.; Rehman, W.; Hussain, S.; Khan, K.M. Triazinoindole analogs as potent inhibitors of α-glucosidase: synthesis, biological evaluation and molecular docking studies. Bioorg. Chem., 2015, 58, 81-87.
[http://dx.doi.org/10.1016/j.bioorg.2014.12.001] [PMID: 25528720]
(b)Taha, M.; Ismail, N.H.; Imran, S.; Rahim, F.; Wadood, A.; Khan, H.; Ullah, H.; Salar, U.; Khan, K.M. Synthesis, β-glucuronidase inhibition and molecular docking studies of hybrid bisindole-thiosemicarbazides analogs. Bioorg. Chem., 2016, 68, 56-63. PMID: 25528720
[http://dx.doi.org/10.1016/j.bioorg.2016.07.008]
[22]
(a)Rahim, F.; Ullah, H.; Javid, M.T.; Wadood, A.; Taha, M.; Ashraf, M.; Shaukat, A.; Junaid, M.; Hussain, S.; Rehman, W.; Mehmood, R.; Sajid, M.; Khan, M.N.; Khan, K.M. Synthesis, in vitro evaluation and molecular docking studies of thiazole derivatives as new inhibitors of α-glucosidase. Bioorg. Chem., 2015, 62, 15-21.
[http://dx.doi.org/10.1016/j.bioorg.2015.06.006] [PMID: 26162519]
(b)Rahim, F.; Javed, M.T.; Ullah, H.; Wadood, A.; Taha, M.; Ashraf, M. Qurat-ul-Ain; Khan, M.A.; Khan, F.; Mirza, S.; Khan, K.M. Synthesis, molecular docking, acetylcholinesterase and butyrylcholinesterase inhibitory potential of thiazole analogs as new inhibitors for Alzheimer disease. Bioorg. Chem., 2015, 62, 106-116. PMID: 26162519
[http://dx.doi.org/10.1016/j.bioorg.2015.08.002]
[23]
(a)Noreen, T.; Taha, M.; Imran, S.; Chigurupati, S.; Rahim, F.; Selvaraj, M.; Ismail, N.H.; Mohammad, J.I.; Ullah, H.; Javid, M.T.; Nawaz, F.; Irshad, M.; Ali, M. Synthesis of align="center" amylase inhibitors based on privileged indole scaffold. Bioorg. Chem., 2017, 72, 248-255.
[http://dx.doi.org/10.1016/j.bioorg.2017.04.010] [PMID: 28482265]
(b)Rahim, F.; Ali, M.; Ullah, S.; Ullah, H.; Taha, M.; Javed, M.T.; Khan, A.A.; Bilal, M. Development of bis-thiobarbiturates as successful urease inhibitors and their molecular modeling studies. Chin. Chem. Lett., 2016, 27, 693-697.
[http://dx.doi.org/10.1016/j.cclet.2015.12.035]
[24]
(a)Taha, M.; Sultan, S.; Nuzar, H.A.; Rahim, F.; Imran, S.; Ismail, N.H.; Naz, H.; Ullah, H. Synthesis and biological evaluation of novel N-arylidenequinoline-3-carbohydrazides as potent β-glucuronidase inhibitors. Bioorg. Med. Chem., 2016, 24(16), 3696-3704.
[http://dx.doi.org/10.1016/j.bmc.2016.06.008] [PMID: 27312423]
(b)Rashid, U.; Rahim, F.; Taha, M.; Arshad, M.; Ullah, H.; Mahmood, T.; Ali, M. Synthesis of 2-acylated and sulfonated 4-hydroxycoumarins: In vitro urease inhibition and molecular docking studies. Bioorg. Chem., 2016, 66, 111-116.
[http://dx.doi.org/10.1016/j.bioorg.2016.04.005] [PMID: 27140727]
[25]
Taha, M.; Imran, S.; Ismail, N.H.; Selvaraj, M.; Rahim, F.; Chigurupati, S.; Ullah, H.; Khan, F.; Salar, U.; Javid, M.T.; Vijayabalan, S.; Zaman, K.; Khan, K.M. Biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives, in vitro align="center"-amylase inhibitory activity and in silico studies. Bioorg. Chem., 2017, 74, 1-9.
[http://dx.doi.org/10.1016/j.bioorg.2017.07.001] [PMID: 28719801]
[26]
(a)Rahim, F.; Malik, F.; Ullah, H.; Wadood, A.; Khan, F.; Javid, M.T.; Taha, M.; Rehman, W.; Ur Rehman, A.; Khan, K.M. Isatin based Schiff bases as inhibitors of α-glucosidase: Synthesis, characterization, in vitro evaluation and molecular docking studies. Bioorg. Chem., 2015, 60, 42-48.
[http://dx.doi.org/10.1016/j.bioorg.2015.03.005] [PMID: 25955493]
(b)Rahim, F.; Ullah, H.; Taha, M.; Wadood, A.; Javed, M.T.; Rehman, W.; Nawaz, M.; Ashraf, M.; Ali, M.; Sajid, M.; Ali, F.; Khan, M.N.; Khan, K.M. Synthesis and in vitro acetylcholinesterase and butyrylcholinesterase inhibitory potential of hydrazide based Schiff bases. Bioorg. Chem., 2016, 68, 30-40.
[http://dx.doi.org/10.1016/j.bioorg.2016.07.005] [PMID: 27441832]
[27]
Taha, M.; Imran, S.; Rahim, F.; Wadood, A.; Khan, K.M. Oxindole based oxadiazole hybrid analogs: Novel α-glucosidase inhibitors. Bioorg. Chem., 2018, 76, 273-280.
[http://dx.doi.org/10.1016/j.bioorg.2017.12.001] [PMID: 29223804]
[28]
Taha, M.; Ismail, N.H.; Imran, S.; Wadood, A.; Rahim, F.; Saad, S.M.; Khan, K.M.; Nasir, A. Synthesis, molecular docking and α-glucosidase inhibition of 5-aryl-2-(6′-nitrobenzofuran-2ʹ-yl)-1,3,4-oxadiazoles. Bioorg. Chem., 2016, 66, 117-123.
[http://dx.doi.org/10.1016/j.bioorg.2016.04.006] [PMID: 27149363]
[29]
Shokrollahzade, S.; Sharifi, F.; Vaseghi, A.; Faridounnia, M.; Jahandideh, S. Protein cold adaptation: Role of physico-chemical parameters in adaptation of proteins to low temperatures. J. Theor. Biol., 2015, 383, 130-137.
[http://dx.doi.org/10.1016/j.jtbi.2015.07.013] [PMID: 26231416]
[30]
Leach, A.R.; Shoichet, B.K.; Peishoff, C.E. Prediction of protein ligand interactions. Docking and scoring: successes and gaps. J. Med. Chem., 2006, 49(20), 5851-5855.
[http://dx.doi.org/10.1021/jm060999m] [PMID: 17004700]
[31]
Liu, M.; Zhang, W.; Wei, J.; Lin, X. Synthesis and α-glucosidase inhibitory mechanisms of bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, a potential marine bromophenol α-glucosidase inhibitor. Mar. Drugs, 2011, 9(9), 1554-1565.
[http://dx.doi.org/10.3390/md9091554] [PMID: 22131958]

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