Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors
Abstract In this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a–n) were designed and synthesized to be evaluated for their anti-α-glucosidase activity, focusing on the fact that α-glucosidase inhibitors have played a significant role in the management of type 2 diabetes me...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-11771-y |
| _version_ | 1811254208887783424 |
|---|---|
| author | Aida Iraji Diba Shareghi-Brojeni Somayeh Mojtabavi Mohammad Ali Faramarzi Tahmineh Akbarzadeh Mina Saeedi |
| author_facet | Aida Iraji Diba Shareghi-Brojeni Somayeh Mojtabavi Mohammad Ali Faramarzi Tahmineh Akbarzadeh Mina Saeedi |
| author_sort | Aida Iraji |
| collection | DOAJ |
| description | Abstract In this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a–n) were designed and synthesized to be evaluated for their anti-α-glucosidase activity, focusing on the fact that α-glucosidase inhibitors have played a significant role in the management of type 2 diabetes mellitus. All synthesized compounds except 9a exhibited excellent inhibitory potential, with IC50 values ranging from 1.00 ± 0.01 to 271.17 ± 0.30 μM when compared to the standard drug acarbose (IC50 = 754.1 ± 0.5 μM). The kinetic binding study indicated that the most active derivatives 9b (IC50 = 1.50 ± 0.01 μM) and 9e (IC50 = 1.00 ± 0.01 μM) behaved as the uncompetitive inhibitors of α-glucosidase with K i = 0.43 and 0.24 μM, respectively. Moreover, fluorescence measurements were conducted to show conformational changes of the enzyme after binding of the most potent inhibitor (9e). Calculation of standard enthalpy (ΔH m°) and entropy (ΔS m°) values confirmed the construction of hydrophobic interactions between 9e and the enzyme. Also, docking studies indicated desired interactions with important residues of the enzyme which rationalized the in vitro results. |
| first_indexed | 2024-04-12T17:03:52Z |
| format | Article |
| id | doaj.art-e276618b1e2c49bf862a00dc80b60c94 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T17:03:52Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e276618b1e2c49bf862a00dc80b60c942022-12-22T03:24:00ZengNature PortfolioScientific Reports2045-23222022-05-0112111510.1038/s41598-022-11771-yCyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitorsAida Iraji0Diba Shareghi-Brojeni1Somayeh Mojtabavi2Mohammad Ali Faramarzi3Tahmineh Akbarzadeh4Mina Saeedi5Stem Cells Technology Research Center, Shiraz University of Medical SciencesDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical SciencesDepartment of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical SciencesDepartment of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical SciencesDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical SciencesPersian Medicine and Pharmacy Research Center, Tehran University of Medical SciencesAbstract In this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a–n) were designed and synthesized to be evaluated for their anti-α-glucosidase activity, focusing on the fact that α-glucosidase inhibitors have played a significant role in the management of type 2 diabetes mellitus. All synthesized compounds except 9a exhibited excellent inhibitory potential, with IC50 values ranging from 1.00 ± 0.01 to 271.17 ± 0.30 μM when compared to the standard drug acarbose (IC50 = 754.1 ± 0.5 μM). The kinetic binding study indicated that the most active derivatives 9b (IC50 = 1.50 ± 0.01 μM) and 9e (IC50 = 1.00 ± 0.01 μM) behaved as the uncompetitive inhibitors of α-glucosidase with K i = 0.43 and 0.24 μM, respectively. Moreover, fluorescence measurements were conducted to show conformational changes of the enzyme after binding of the most potent inhibitor (9e). Calculation of standard enthalpy (ΔH m°) and entropy (ΔS m°) values confirmed the construction of hydrophobic interactions between 9e and the enzyme. Also, docking studies indicated desired interactions with important residues of the enzyme which rationalized the in vitro results.https://doi.org/10.1038/s41598-022-11771-y |
| spellingShingle | Aida Iraji Diba Shareghi-Brojeni Somayeh Mojtabavi Mohammad Ali Faramarzi Tahmineh Akbarzadeh Mina Saeedi Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors Scientific Reports |
| title | Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors |
| title_full | Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors |
| title_fullStr | Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors |
| title_full_unstemmed | Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors |
| title_short | Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors |
| title_sort | cyanoacetohydrazide linked to 1 2 3 triazole derivatives a new class of α glucosidase inhibitors |
| url | https://doi.org/10.1038/s41598-022-11771-y |
| work_keys_str_mv | AT aidairaji cyanoacetohydrazidelinkedto123triazolederivativesanewclassofaglucosidaseinhibitors AT dibashareghibrojeni cyanoacetohydrazidelinkedto123triazolederivativesanewclassofaglucosidaseinhibitors AT somayehmojtabavi cyanoacetohydrazidelinkedto123triazolederivativesanewclassofaglucosidaseinhibitors AT mohammadalifaramarzi cyanoacetohydrazidelinkedto123triazolederivativesanewclassofaglucosidaseinhibitors AT tahminehakbarzadeh cyanoacetohydrazidelinkedto123triazolederivativesanewclassofaglucosidaseinhibitors AT minasaeedi cyanoacetohydrazidelinkedto123triazolederivativesanewclassofaglucosidaseinhibitors |