Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies
Inhibition of α-glucosidase and α-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-b] quinoxalines-carrying thiazole hybrids 1–17 were created and described using NMR. All analogues were tested for...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2024.2367128 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850252080319561728 |
|---|---|
| author | Nirvana A. Gohar Eman A. Fayed Yousry A. Ammar Ola A. Abu Ali Ahmed Ragab Amal M. Mahfoz Moustafa S. Abusaif |
| author_facet | Nirvana A. Gohar Eman A. Fayed Yousry A. Ammar Ola A. Abu Ali Ahmed Ragab Amal M. Mahfoz Moustafa S. Abusaif |
| author_sort | Nirvana A. Gohar |
| collection | DOAJ |
| description | Inhibition of α-glucosidase and α-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-b] quinoxalines-carrying thiazole hybrids 1–17 were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds 4, 6, 8, and 16 were the most potent among the synthesised analogues. These hybrids were examined for their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, and total cholesterol. Moreover, these compounds were tested against α-glucosidase and α-amylase enzymes in vitro. The four hybrids 4, 6, 8, and 16 represented moderate to potent activity with IC50 values 0.982 ± 0.04, to 10.19 ± 0.21 for α-glucosidase inhibition and 17.58 ± 0.74 to 121.6 ± 5.14 μM for α-amylase inhibition when compared to the standard medication acarbose with IC50=0.316 ± 0.02 μM for α-glucosidase inhibition and 31.56 ± 1.33 μM for α-amylase inhibition. Docking studies as well as in silico ADMT were done. |
| format | Article |
| id | doaj-art-ab49fb0c93f841ccab6342a242b07780 |
| institution | OA Journals |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-ab49fb0c93f841ccab6342a242b077802025-08-20T01:57:44ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2367128Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studiesNirvana A. Gohar0Eman A. Fayed1Yousry A. Ammar2Ola A. Abu Ali3Ahmed Ragab4Amal M. Mahfoz5Moustafa S. Abusaif6Department of Pharmaceutical Organic Chemistry, Modern University for Technology and Information, Cairo, EgyptDepartment of Pharmaceutical Organic Chemistry, Al-Azhar University, Nasr City, Cairo, EgyptDepartment of Chemistry, , Al-Azhar University, Nasr City, Cairo, EgyptDepartment of Chemistry, College of Science, Taif University, Taif, Saudi ArabiaDepartment of Chemistry, , Al-Azhar University, Nasr City, Cairo, EgyptDepartment of Pharmacology and Toxicology, , Modern University for Technology and Information, Cairo, EgyptDepartment of Chemistry, , Al-Azhar University, Nasr City, Cairo, EgyptInhibition of α-glucosidase and α-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-b] quinoxalines-carrying thiazole hybrids 1–17 were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds 4, 6, 8, and 16 were the most potent among the synthesised analogues. These hybrids were examined for their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, and total cholesterol. Moreover, these compounds were tested against α-glucosidase and α-amylase enzymes in vitro. The four hybrids 4, 6, 8, and 16 represented moderate to potent activity with IC50 values 0.982 ± 0.04, to 10.19 ± 0.21 for α-glucosidase inhibition and 17.58 ± 0.74 to 121.6 ± 5.14 μM for α-amylase inhibition when compared to the standard medication acarbose with IC50=0.316 ± 0.02 μM for α-glucosidase inhibition and 31.56 ± 1.33 μM for α-amylase inhibition. Docking studies as well as in silico ADMT were done.https://www.tandfonline.com/doi/10.1080/14756366.2024.2367128α-Amylaseα-GlucosidaseFluorinated indeno-quinoxaline |
| spellingShingle | Nirvana A. Gohar Eman A. Fayed Yousry A. Ammar Ola A. Abu Ali Ahmed Ragab Amal M. Mahfoz Moustafa S. Abusaif Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies Journal of Enzyme Inhibition and Medicinal Chemistry α-Amylase α-Glucosidase Fluorinated indeno-quinoxaline |
| title | Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies |
| title_full | Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies |
| title_fullStr | Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies |
| title_full_unstemmed | Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies |
| title_short | Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies |
| title_sort | fluorinated indeno quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α amylase and α glucosidase synthesis molecular docking and admet studies |
| topic | α-Amylase α-Glucosidase Fluorinated indeno-quinoxaline |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2024.2367128 |
| work_keys_str_mv | AT nirvanaagohar fluorinatedindenoquinoxalinebearingthiazolemoietiesashypoglycaemicagentstargetingaamylaseandaglucosidasesynthesismoleculardockingandadmetstudies AT emanafayed fluorinatedindenoquinoxalinebearingthiazolemoietiesashypoglycaemicagentstargetingaamylaseandaglucosidasesynthesismoleculardockingandadmetstudies AT yousryaammar fluorinatedindenoquinoxalinebearingthiazolemoietiesashypoglycaemicagentstargetingaamylaseandaglucosidasesynthesismoleculardockingandadmetstudies AT olaaabuali fluorinatedindenoquinoxalinebearingthiazolemoietiesashypoglycaemicagentstargetingaamylaseandaglucosidasesynthesismoleculardockingandadmetstudies AT ahmedragab fluorinatedindenoquinoxalinebearingthiazolemoietiesashypoglycaemicagentstargetingaamylaseandaglucosidasesynthesismoleculardockingandadmetstudies AT amalmmahfoz fluorinatedindenoquinoxalinebearingthiazolemoietiesashypoglycaemicagentstargetingaamylaseandaglucosidasesynthesismoleculardockingandadmetstudies AT moustafasabusaif fluorinatedindenoquinoxalinebearingthiazolemoietiesashypoglycaemicagentstargetingaamylaseandaglucosidasesynthesismoleculardockingandadmetstudies |