Login Register Cart 0
Generic placeholder image

Letters in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

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

Ugi Adducts: Design and Synthesis of Natural-based α-glucosidase Inhibitors

Author(s): Aida Iraji, Mina Saeedi, Tina Rafiee-Sereshky, Somayeh Mojtabavi, Mohammad Ali Faramarzi and Tahmineh Akbarzadeh*

Volume 19, Issue 12, 2022

Published on: 10 June, 2022

Page: [1084 - 1093] Pages: 10

DOI: 10.2174/1570178619666220401143634

Price: $65

Abstract

Background: α-Glucosidase inhibitors have been found as the main tool for the treatment of type 2 diabetes. In this respect, the synthesis of a new series of amino-oxoethylcinnamamide derivatives containing α,β-unsaturated carbonyl-based moiety, was developed to be evaluated for their anti-α- glucosidase activity.

Methods: The title compounds were synthesized via the Ugi reaction of cinnamic acid, isocyanides, aromatic aldehydes, and amine derivatives at ambient temperature. All newly synthesized derivatives were screened for their in vitro α-glucosidase inhibitory activity.

Results: Among synthesized compounds, derivative 5b displayed promising anti-α-glucosidase activity (IC50 = 115.6 μM), approximately 6-fold more potent than the standard drug (acarbose, IC50 = 750.0 μM). Moreover, kinetic characterization of enzyme inhibition was performed to understand the mechanism of inhibition. To determine the mode of binding interactions of prepared compounds with the enzyme, molecular docking studies were also conducted.

Conclusion: Ugi products merit to be investigated in anti-diabetic drug discovery developments.

Keywords: Diabetes, α-Glucosidase, molecular docking, synthesis, Ugi reaction, inhibitor.

« Previous Next »
Graphical Abstract

[1]
Heron, M. Natl. Vital Stat. Rep., 2018, 67(6), 1-77.
[PMID: 30248017]
[2]
Whiting, D.R.; Guariguata, L.; Weil, C.; Shaw, J. Diabetes Res. Clin. Pract., 2011, 94(3), 311-321.
[http://dx.doi.org/10.1016/j.diabres.2011.10.029] [PMID: 22079683]
[3]
IDF Diabetes Atlas. 2015. Available from: https://www.diabetesatlas.org/upload/resources/previous/files/7/IDF%20Diabetes%20Atlas%207th.pdf
[4]
Alberti, K.G.; Zimmet, P.Z. Diabet. Med., 1998, 15(7), 539-553.
[http://dx.doi.org/10.1002/(SICI)1096-9136(199807)15:7<539:AID-DIA668>3.0.CO;2-S] [PMID: 9686693]
[5]
Asmat, U.; Abad, K.; Ismail, K. Saudi Pharm. J., 2016, 24(5), 547-553.
[http://dx.doi.org/10.1016/j.jsps.2015.03.013] [PMID: 27752226]
[6]
Moghaddam, F.M.; Daneshfar, M.; Daneshfar, Z.; Iraji, A.; Samandari-Najafabad, A.; Faramarzi, M.A.; Mahdavi, M. J. Mol. Struct., 2022, 1250, 131726.
[http://dx.doi.org/10.1016/j.molstruc.2021.131726]
[7]
Toender, A.; Vestergaard, M.; Munk-Olsen, T.; Larsen, J.T.; Kristensen, J.K.; Laursen, T.M. Schizophr. Res., 2020, 218, 99-106.
[http://dx.doi.org/10.1016/j.schres.2020.01.024] [PMID: 32029352]
[8]
Paul, S.; Ali, A.; Katare, R. J. Diabetes Complications, 2020, 34(8), 107613.
[http://dx.doi.org/10.1016/j.jdiacomp.2020.107613] [PMID: 32505477]
[9]
Gan, Q.; Wang, J.; Hu, J.; Lou, G.; Xiong, H.; Peng, C.; Zheng, S.; Huang, Q. J. Steroid Biochem. Mol. Biol., 2020, 198, 105575.
[http://dx.doi.org/10.1016/j.jsbmb.2019.105575]
[10]
Remedi, M.S.; Emfinger, C. Diabetes Obes. Metab., 2016, 18(Suppl. 1), 110-116.
[http://dx.doi.org/10.1111/dom.12727] [PMID: 27615139]
[11]
Goldstein, B.J.; Müller-Wieland, D. Type 2 Diabetes: Principles and Practice, 2nd ed; CRC Press, 2016.
[http://dx.doi.org/10.3109/9780849379581]
[12]
Brătilă, E.; Iacob, G.; Comandașu, D.-E.; Mitran, M.; Cîrstoiu, M.; Bohâlțea, R.; Berceanu, C.; Mehedințu, C.; Vlădăreanu, S. Gineco.eu, 2016, 12, 183-186.
[13]
Dhameja, M.; Gupta, P. Eur. J. Med. Chem., 2019, 176, 343-377.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.025] [PMID: 31112894]
[14]
Santos, C.M.M.; Freitas, M.; Fernandes, E. Eur. J. Med. Chem., 2018, 157, 1460-1479.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.073] [PMID: 30282319]
[15]
Abuelizz, H.A.; Anouar, E.H.; Ahmad, R.; Azman, N.I.I.N.; Marzouk, M.; Al-Salahi, R. PLoS One, 2019, 14(8), e0220379.
[http://dx.doi.org/10.1371/journal.pone.0220379] [PMID: 31412050]
[16]
Gollapalli, M.; Taha, M.; Ullah, H.; Nawaz, M.; AlMuqarrabun, L.M.R.; Rahim, F.; Qureshi, F.; Mosaddik, A.; Ahmat, N.; Khan, K.M. Bioorg. Chem., 2018, 80, 112-120.
[http://dx.doi.org/10.1016/j.bioorg.2018.06.001] [PMID: 29894890]
[17]
Liu, Y.; Ke, Z.; Cui, J.; Chen, W-H.; Ma, L.; Wang, B. Bioorg. Med. Chem., 2008, 16(15), 7185-7192.
[http://dx.doi.org/10.1016/j.bmc.2008.06.043] [PMID: 18632275]
[18]
Chaudhry, F.; Choudhry, S.; Huma, R.; Ashraf, M.; Al-Rashida, M.; Munir, R.; Sohail, R.; Jahan, B.; Munawar, M.A.; Khan, M.A. Bioorg. Chem., 2017, 73, 1-9.
[http://dx.doi.org/10.1016/j.bioorg.2017.05.009] [PMID: 28521172]
[19]
Karami, M.; Hasaninejad, A.; Mahdavi, H.; Iraji, A.; Mojtabavi, S.; Faramarzi, M.A.; Mahdavi, M. Mol. Divers., 2021, 1-3.
[20]
Panahi, F.; Yousefi, R.; Mehraban, M.H.; Khalafi-Nezhad, A. Carbohydr. Res., 2013, 380, 81-91.
[http://dx.doi.org/10.1016/j.carres.2013.07.008] [PMID: 23978663]
[21]
Wang, G.; Peng, Z.; Wang, J.; Li, X.; Li, J. Eur. J. Med. Chem., 2017, 125, 423-429.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.067] [PMID: 27689725]
[22]
Gurram, V.; Garlapati, R.; Thulluri, C.; Madala, N.; Kasani, K.S.; Machiraju, P.K.; Chaudhary, A.B.; Addepally, U.; Dayam, R.; Chunduri, V.R.; Patro, B. Med. Chem. Res., 2015, 24(5), 2227-2237.
[http://dx.doi.org/10.1007/s00044-014-1293-5]
[23]
Saeedi, M.; Raeisi-Nafchi, M.; Sobhani, S.; Mirfazli, S.S.; Zardkanlou, M.; Mojtabavi, S.; Faramarzi, M.A.; Akbarzadeh, T. Mol. Divers., 2021, 25(4), 2399-2409.
[http://dx.doi.org/10.1007/s11030-020-10137-8] [PMID: 33047276]
[24]
Saeedi, M.; Eslami, A.; Mirfazli, S.S.; Zardkanlou, M.; Faramarzi, M.A.; Mahdavi, M.; Akbarzadeh, T. Lett. Drug Des. Discov., 2021, 18(5), 436-344.
[http://dx.doi.org/10.2174/1570180817999201104125018]
[25]
Shareghi-Boroujeni, D.; Iraji, A.; Mojtabavi, S.; Faramarzi, M.A.; Akbarzadeh, T.; Saeedi, M. Bioorg. Chem., 2021, 111, 104869.
[http://dx.doi.org/10.1016/j.bioorg.2021.104869] [PMID: 33839583]
[26]
Esfahani, A.N.; Iraji, A.; Alamir, A.; Moradi, S.; Asgari, M.S.; Hosseini, S.; Mojtabavi, S.; Nasli-Esfahani, E.; Faramarzi, M.A.; Bandarian, F.; Larijani, B.; Hamedifar, H.; Hajimiri, M.H.; Mahdavi, M. Mol. Divers., 2021, 1-15.
[27]
Mollica, A.; Zengin, G.; Durdagi, S.; Ekhteiari Salmas, R.; Macedonio, G.; Stefanucci, A.; Dimmito, M.P.; Novellino, E. J. Biomol. Struct. Dyn., 2019, 37(3), 726-740.
[http://dx.doi.org/10.1080/07391102.2018.1439403] [PMID: 29421954]
[28]
Phuwapraisirisan, P.; Puksasook, T.; Jong-Aramruang, J.; Kokpol, U. Bioorg. Med. Chem. Lett., 2008, 18(18), 4956-4958.
[http://dx.doi.org/10.1016/j.bmcl.2008.08.024] [PMID: 18760601]
[29]
Song, Y.H.; Kim, D.W.; Curtis-Long, M.J.; Park, C.; Son, M.; Kim, J.Y.; Yuk, H.J.; Lee, K.W.; Park, K.H. Eur. J. Med. Chem., 2016, 114, 201-208.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.044] [PMID: 26974386]
[30]
Rocha, R.O.; Rodrigues, M.O.; Neto, B.A.D. ACS Omega, 2020, 5(2), 972-979.
[http://dx.doi.org/10.1021/acsomega.9b03684] [PMID: 31984252]
[31]
Joshi, S.R.; Standl, E.; Tong, N.; Shah, P.; Kalra, S.; Rathod, R. Expert Opin. Pharmacother., 2015, 16, 1959-1981.
[http://dx.doi.org/10.1517/14656566.2015.1070827] [PMID: 26255950]
[32]
Dabhi, A.S.; Bhatt, N.R.; Shah, M.J. J. Clin. Diagn. Res., 2013, 7(12), 3023-3027.
[PMID: 24551718]
[33]
Chiasson, J-L.; Josse, R.G.; Gomis, R.; Hanefeld, M.; Karasik, A.; Laakso, M. Lancet, 2002, 359(9323), 2072-2077.
[http://dx.doi.org/10.1016/S0140-6736(02)08905-5] [PMID: 12086760]
[34]
Saeedi, M.; Hadjiakhondi, A.; Nabavi, S.M.; Manayi, A. Curr. Top. Med. Chem., 2017, 17(4), 428-440.
[http://dx.doi.org/10.2174/1568026616666160824104655] [PMID: 27558678]
[35]
Ghani, U. Eur. J. Med. Chem., 2015, 103, 133-162.
[http://dx.doi.org/10.1016/j.ejmech.2015.08.043] [PMID: 26344912]
[36]
Mottaghipisheh, J.; Taghrir, H.; Boveiri Dehsheikh, A.; Zomorodian, K.; Irajie, C.; Mahmoodi Sourestani, M.; Iraji, A. Pharmaceuticals (Basel), 2021, 14(11), 1104.
[http://dx.doi.org/10.3390/ph14111104] [PMID: 34832886]
[37]
Islam, M.S.; Barakat, A.; Al-Majid, A.M.; Ghabbour, H.A.; Rahman, A.F.M.M.; Javaid, K.; Imad, R.; Yousuf, S.; Choudhary, M.I. Bioorg. Med. Chem., 2016, 24(8), 1675-1682.
[http://dx.doi.org/10.1016/j.bmc.2016.02.037] [PMID: 26972921]
[38]
Saeedi, M.; Mohammadi-Khanaposhtani, M.; Asgari, M.S.; Eghbalnejad, N.; Imanparast, S.; Faramarzi, M.A.; Larijani, B.; Mahdavi, M.; Akbarzadeh, T. Bioorg. Med. Chem., 2019, 27(23), 115148.
[http://dx.doi.org/10.1016/j.bmc.2019.115148] [PMID: 31679980]
[39]
Saeedi, M.; Mohammadi-Khanaposhtani, M.; Pourrabia, P.; Razzaghi, N.; Ghadimi, R.; Imanparast, S.; Faramarzi, M.A.; Bandarian, F.; Esfahani, E.N.; Safavi, M.; Rastegar, H.; Larijani, B.; Mahdavi, M.; Akbarzadeh, T. Bioorg. Chem., 2019, 83, 161-169.
[http://dx.doi.org/10.1016/j.bioorg.2018.10.023] [PMID: 30366316]

Rights & Permissions Print Cite
Article Metrics
11
© 2024 Bentham Science Publishers | Privacy Policy