Abstract
We have designed and synthesized phthalimide-Schiff base-coumarin hybrids 8a–b, 9a–d, 10a–b, and 11a–d and evaluated them for α-glucosidase inhibitory potential against yeast form of this enzyme. For the synthesis of title compounds 4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, 2-hydroxybenzaldehyde, 2-hydroxybenzaldehyde derivatives, coumarin-3-carbohydrazide, and coumarin-7-yloxy-acetohydrazide were used. In vitro α-glucosidase inhibition revealed that all the synthesized compounds exhibited outstanding α-glucosidase inhibition with IC50 values ranging between 85.2 ± 1.7 and 577.7 ± 7.5 µM when compared with the standard inhibitor acarbose having IC50 value 750.0 ± 12.0 µM. The most potent compounds were 4-hydroxybenzaldehyde derivative 8a with coumarin-3-carbohydrazide moiety, 2-hydroxy-5-nitrobenzaldehyde derivative 11d with coumarin-7-yloxy-acetohydrazide moiety, and 2-hydroxy-5-nitrobenzaldehyde derivative 9d with coumarin-3-carbohydrazide moiety. Molecular docking studies were carried out to understand the interaction modes and binding energies of the most active compounds and standard drug acarbose. This studies predicted that compounds 8a, 11d, and 9d (respectively with binding energies = − 10.77, − 8.65, and − 8.66 kcal/mol) bind to active site α-glucosidase more easily than acarbose (binding energy = − 4.04 kcal/mol).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adib M, Peytam F, Rahmanian-Jazi M, Mahernia S, Bijanzadeh HR, Jahani M, Mohammadi-Khanaposhtani M, Imanparast S, Faramarzi MA, Mahdavi M, Larijani B (2018) New 6-amino-pyrido [2, 3-d] pyrimidine-2, 4-diones as novel agents to treat type 2 diabetes: a simple and efficient synthesis, α-glucosidase inhibition, molecular modeling and kinetic study. Eur J Med Chem 155:353–363. https://doi.org/10.1016/j.ejmech.2018.05.046
AG HBB (1994) Pharmacology of α-glucosidase inhibition. Eur J Clin Investig 24:3–10
Atkinson MA, Eisenbarth GS (2001) Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358:221–229. https://doi.org/10.1016/S0140-6736(01)05415-0
Cheng AY, Fantus IG (2005) Oral antihyperglycemic therapy for type 2 diabetes mellitus. CMAJ 172:213–226. https://doi.org/10.1503/cmaj.1031414
Hollander P (1992) Safety profile of acarbose, an α-glucosidase inhibitor. Drugs 44:47–53. https://doi.org/10.2165/00003495-199200443-00007
Imran S, Taha M, Ismail NH, Kashif SM, Rahim F, Jamil W, Hariono M, Yusuf M, Wahab H (2015) Synthesis of novel flavone hydrazones: in-vitro evaluation of α-glucosidase inhibition, QSAR analysis and docking studies. Eur J Med Chem 105:156–170. https://doi.org/10.1016/j.ejmech.2015.10.017
Kahn SE, Cooper ME, Del Prato S (2014) Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 383:1068–1083. https://doi.org/10.1016/S0140-6736(13)62154-6
Mohammadi-Khanaposhtani M, Yahyavi H, Barzegaric E, Imanparast S, Heravi MM, Ali Faramarzi M, Foroumadi A, Adibi H, Larijani B, Mahdavi M (2018) New biscoumarin derivatives as potent α-glucosidase inhibitors: synthesis, biological evaluation, kinetic analysis, and docking study. Polycycl Aromat Compd 5:1–12
Nagarapu L, Mateti J, Gaikwad HK, Bantu R, Rani MS, Subhashini NP (2011) Synthesis and anti-inflammatory activity of some novel 3-phenyl-N-[3-(4-phenylpiperazin-1yl) propyl]-1H-pyrazole-5-carboxamide derivatives. Bioorg Med Chem Lett 21:4138–4140. https://doi.org/10.1016/j.bmcl.2011.05.105
Pascale R, Carocci A, Catalano A, Lentini G, Spagnoletta A, Cavalluzzi MM, De Santis F, De Palma A, Scalera V, Franchini C (2010) New N-(phenoxydecyl) phthalimide derivatives displaying potent inhibition activity towards α-glucosidase. Bioorg Med Chem 18:5903–5914. https://doi.org/10.1016/j.bmc.2010.06.088
Saltiel AR (2001) New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell 104:517–529. https://doi.org/10.1016/S0092-8674(01)00239-2
Secci D, Carradori S, Bolasco A, Chimenti P, Yáñez M, Ortuso F, Alcaro S (2011) Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido coumarin derivatives. Eur J Med Chem 46:4846–4852. https://doi.org/10.1016/j.ejmech.2011.07.017
Sharma U, Kumar P, Kumar N, Singh B (2010) Recent advances in the chemistry of phthalimide analogues and their therapeutic potential. Mini Rev Med Chem 10:678–704. https://doi.org/10.2174/138955710791572442
Singh P, Ngcoya N, Mopuri R, Kerru N, Manhas N, Ebenezer O, Islam MS (2018) α-Glucosidase inhibition, antioxidant and docking studies of hydroxycoumarins and their mono and bis O-alkylated/acetylated analogs. Lett Drug Des Discov 15:127–135. https://doi.org/10.2174/1570180814666170602081941
Taha M, Ismail NH, Imran S, Rokei MQ, Saad SM, Khan KM (2015) Synthesis of new oxadiazole derivatives as α-glucosidase inhibitors. Bioorg Med Chem 23:4155–4162. https://doi.org/10.1016/j.bmc.2015.06.060
Taha M, Shah SA, Afifi M, Imran S, Sultan S, Rahim F, Khan KM (2018) Synthesis, α-glucosidase inhibition and molecular docking study of coumarin based derivatives. Bioorg Chem 77:586–592. https://doi.org/10.1016/j.bioorg.2018.01.033
Wang G, Wang J, He D, Li X, Li J, Peng Z (2017) Synthesis, in vitro evaluation and molecular docking studies of novel coumarin-isatin derivatives as α-glucosidase inhibitors. Chem Biol Drug Des 89:456–463. https://doi.org/10.1111/cbdd.12867
Xu XT, Deng XY, Chen J, Liang QM, Zhang K, Li DL, Wu PP, Zheng X, Zhou RP, Jiang ZY, Ma AJ (2020) Synthesis and biological evaluation of coumarin derivatives as α-glucosidase inhibitors. Eur J Med Chem 189:112013. https://doi.org/10.1016/j.ejmech.2019.112013
Zawawi NK, Taha M, Ahmat N, Wadood A, Ismail NH, Rahim F, Azam SS, Abdullah N (2016) Benzimidazole derivatives as new α-glucosidase inhibitors and in silico studies. Bioorg Chem 64:29–36. https://doi.org/10.1016/j.bioorg.2015.11.006
Author information
Authors and Affiliations
Corresponding authors
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Sherafati, M., Mohammadi-Khanaposhtani, M., Moradi, S. et al. Design, synthesis and biological evaluation of novel phthalimide-Schiff base-coumarin hybrids as potent α-glucosidase inhibitors. Chem. Pap. 74, 4379–4388 (2020). https://doi.org/10.1007/s11696-020-01246-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11696-020-01246-7