Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico study
Twenty-five analogs were synthesized based on 1,3,4-thiadiazole-fused-[1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety (1–25) and then tested for the antidiabetic profile. The entire afforded derivatives showed varied inhibition profiles ranging between 0.70 ± 0.01 and 30.80 ± 0.80 μM (agai...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.1023316/full |
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| author | Rafaqat Hussain Mazloom Shah Shahid Iqbal Wajid Rehman Shoaib Khan Liaqat Rasheed Haseena Naz Hanan A. Al-ghulikah Eslam B. Elkaeed Rami Adel Pashameah Eman Alzahrani Abd-ElAziem Farouk |
| author_facet | Rafaqat Hussain Mazloom Shah Shahid Iqbal Wajid Rehman Shoaib Khan Liaqat Rasheed Haseena Naz Hanan A. Al-ghulikah Eslam B. Elkaeed Rami Adel Pashameah Eman Alzahrani Abd-ElAziem Farouk |
| author_sort | Rafaqat Hussain |
| collection | DOAJ |
| description | Twenty-five analogs were synthesized based on 1,3,4-thiadiazole-fused-[1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety (1–25) and then tested for the antidiabetic profile. The entire afforded derivatives showed varied inhibition profiles ranging between 0.70 ± 0.01 and 30.80 ± 0.80 μM (against α-amylase) in comparison to standard acarbose (12.80 ± 0.10 μM). Similarly, synthetics analogs also displayed a varied range of α-glucosidase activity ranging from 0.80 ± 0.01 μM to IC50 = 29.70 ± 0.40 μM (against α-glucosidase) as compared to standard acarbose (IC50 = 12.90 ± 0.10 μM). Among synthesized analogs, compound 22 showed excellent potency due to the presence of di-hydroxy substitutions at the 2,3-position of the aryl ring. For all analogs, the structure–activity relationship was carried out based on the pattern of substitutions around the aryl ring, and further, the potent analogs were subjected to a molecular docking study to analyze how active residues of targeted enzymes interact with active parts of newly prepared analogs. The result obtained shows that these compounds furnish several key interactions with enzyme active sites and, hence, enhanced their enzymatic activities. |
| first_indexed | 2024-04-13T18:38:32Z |
| format | Article |
| id | doaj.art-035b96c7ad194d4a89aa48659fd557e8 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-13T18:38:32Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-035b96c7ad194d4a89aa48659fd557e82022-12-22T02:34:47ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-10-011010.3389/fchem.2022.10233161023316Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico studyRafaqat Hussain0Mazloom Shah1Shahid Iqbal2Wajid Rehman3Shoaib Khan4Liaqat Rasheed5Haseena Naz6Hanan A. Al-ghulikah7Eslam B. Elkaeed8Rami Adel Pashameah9Eman Alzahrani10Abd-ElAziem Farouk11Department of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, PakistanDepartment of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad, PakistanDepartment of Chemistry, School of Natural Sciences (SNS), National University of Science and Technology (NUST), Islamabad, PakistanDepartment of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, PakistanDepartment of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, PakistanDepartment of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, PakistanDepartment of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, PakistanDepartment of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, Saudi ArabiaDepartment of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah, Saudi ArabiaDepartment of Chemistry, College of Science, Taif University, Taif, Saudi ArabiaDepartment of Biotechnology College of Science, Taif University, Taif, Saudi ArabiaTwenty-five analogs were synthesized based on 1,3,4-thiadiazole-fused-[1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety (1–25) and then tested for the antidiabetic profile. The entire afforded derivatives showed varied inhibition profiles ranging between 0.70 ± 0.01 and 30.80 ± 0.80 μM (against α-amylase) in comparison to standard acarbose (12.80 ± 0.10 μM). Similarly, synthetics analogs also displayed a varied range of α-glucosidase activity ranging from 0.80 ± 0.01 μM to IC50 = 29.70 ± 0.40 μM (against α-glucosidase) as compared to standard acarbose (IC50 = 12.90 ± 0.10 μM). Among synthesized analogs, compound 22 showed excellent potency due to the presence of di-hydroxy substitutions at the 2,3-position of the aryl ring. For all analogs, the structure–activity relationship was carried out based on the pattern of substitutions around the aryl ring, and further, the potent analogs were subjected to a molecular docking study to analyze how active residues of targeted enzymes interact with active parts of newly prepared analogs. The result obtained shows that these compounds furnish several key interactions with enzyme active sites and, hence, enhanced their enzymatic activities.https://www.frontiersin.org/articles/10.3389/fchem.2022.1023316/fullsynthesis4-benzodioxinthiadiazole-fused-[1,4]-thiadiazoleα-amylaseα-glucosidasemolecular docking |
| spellingShingle | Rafaqat Hussain Mazloom Shah Shahid Iqbal Wajid Rehman Shoaib Khan Liaqat Rasheed Haseena Naz Hanan A. Al-ghulikah Eslam B. Elkaeed Rami Adel Pashameah Eman Alzahrani Abd-ElAziem Farouk Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico study Frontiers in Chemistry synthesis 4-benzodioxin thiadiazole-fused-[1,4]-thiadiazole α-amylase α-glucosidase molecular docking |
| title | Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico study |
| title_full | Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico study |
| title_fullStr | Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico study |
| title_full_unstemmed | Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico study |
| title_short | Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico study |
| title_sort | molecular iodine promoted oxidative cyclization for the synthesis of 1 3 4 thiadiazole fused 1 2 4 thiadiazole incorporating 1 4 benzodioxine moiety as potent inhibitors of α amylase and α glucosidase in vitro and in silico study |
| topic | synthesis 4-benzodioxin thiadiazole-fused-[1,4]-thiadiazole α-amylase α-glucosidase molecular docking |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.1023316/full |
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