Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study
Diabetes mellitus is one of the most chronic metabolic diseases. In the past few years, our research group has synthesized and evaluated libraries of heterocyclic analogs against α-glucosidase and α-amylase enzymes and found encouraging results. The current study comprises the evaluation of benzimid...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/20/6921 |
| _version_ | 1827648626395971584 |
|---|---|
| author | Hayat Ullah Shoaib Khan Fazal Rahim Muhammad Taha Rashid Iqbal Maliha Sarfraz Syed Adnan Ali Shah Muhammad Sajid Mohamed F. Awad Awatif Omran Marzough Aziz Albalawi Mahmoud A. Abdelaziz Azza Al Areefy Ibrahim Jafri |
| author_facet | Hayat Ullah Shoaib Khan Fazal Rahim Muhammad Taha Rashid Iqbal Maliha Sarfraz Syed Adnan Ali Shah Muhammad Sajid Mohamed F. Awad Awatif Omran Marzough Aziz Albalawi Mahmoud A. Abdelaziz Azza Al Areefy Ibrahim Jafri |
| author_sort | Hayat Ullah |
| collection | DOAJ |
| description | Diabetes mellitus is one of the most chronic metabolic diseases. In the past few years, our research group has synthesized and evaluated libraries of heterocyclic analogs against α-glucosidase and α-amylase enzymes and found encouraging results. The current study comprises the evaluation of benzimidazole-bearing thiosemicarbazone as antidiabetic agents. A library of fifteen derivatives (<b>7</b>–<b>21</b>) was synthesized, characterized via different spectroscopic techniques such as HREI-MS, NMR, and screened against α-glucosidase and α-amylase enzymes. All derivatives exhibited excellent to good biological inhibitory potentials. Derivatives <b>19</b> (IC<sub>50</sub> = 1.30 ± 0.20 µM and 1.20 ± 0.20 µM) and <b>20</b> (IC<sub>50</sub> = 1.60 ± 0.20 µM and 1.10 ± 0.01 µM) were found to be the most potent among the series when compared with standard drug acarbose (IC<sub>50</sub> = 11.29 ± 0.07 and 11.12 ± 0.15 µM, respectively). These derivatives may potentially serve as the lead candidates for the development of new therapeutic representatives. The structure–activity relationship was carried out for all molecules which are mainly based upon the pattern of substituent/s on phenyl rings. Moreover, in silico docking studies were carried out to investigate the active binding mode of selected derivatives with the target enzymes. |
| first_indexed | 2024-03-09T19:42:47Z |
| format | Article |
| id | doaj.art-d44c5e8ff2ce41f89253429c86a2c56d |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T19:42:47Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-d44c5e8ff2ce41f89253429c86a2c56d2023-11-24T01:33:59ZengMDPI AGMolecules1420-30492022-10-012720692110.3390/molecules27206921Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking StudyHayat Ullah0Shoaib Khan1Fazal Rahim2Muhammad Taha3Rashid Iqbal4Maliha Sarfraz5Syed Adnan Ali Shah6Muhammad Sajid7Mohamed F. Awad8Awatif Omran9Marzough Aziz Albalawi10Mahmoud A. Abdelaziz11Azza Al Areefy12Ibrahim Jafri13Department of Chemistry, University of Okara, Okara 56300, PakistanDepartment of Chemistry, Hazara University, Mansehra 21120, PakistanDepartment of Chemistry, Hazara University, Mansehra 21120, PakistanDepartment of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi ArabiaDepartment of Agronomy, Faculty of Agriculture and Environment, The Islamia University of Bahawalpur, Bahawalpur 63100, PakistanDepartment of Zoology, Wildlife and Fisheries, University of Agriculture Faisalabad, Sub-Campus Toba Tek Singh, Punjab 36050, PakistanFaculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam, Selangor 42300, MalaysiaDepartment of Biochemistry, Hazara University, Mansehra 21120, PakistanDepartment of Biology, College of Science, Taif University, Taif 21944, Saudi ArabiaDepartment of Biochemistry, College of Science, University of Tabuk, Tabuk 71491, Saudi ArabiaDepartment of Chemistry, Alwajh College, University of Tabuk, Tabuk 71491, Saudi ArabiaDepartment of Chemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi ArabiaClinical Nutrition Department, Applied Medical Science Collage, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Biotechnology, Faculty of Sciences, Taif University, Taif 21944, Saudi ArabiaDiabetes mellitus is one of the most chronic metabolic diseases. In the past few years, our research group has synthesized and evaluated libraries of heterocyclic analogs against α-glucosidase and α-amylase enzymes and found encouraging results. The current study comprises the evaluation of benzimidazole-bearing thiosemicarbazone as antidiabetic agents. A library of fifteen derivatives (<b>7</b>–<b>21</b>) was synthesized, characterized via different spectroscopic techniques such as HREI-MS, NMR, and screened against α-glucosidase and α-amylase enzymes. All derivatives exhibited excellent to good biological inhibitory potentials. Derivatives <b>19</b> (IC<sub>50</sub> = 1.30 ± 0.20 µM and 1.20 ± 0.20 µM) and <b>20</b> (IC<sub>50</sub> = 1.60 ± 0.20 µM and 1.10 ± 0.01 µM) were found to be the most potent among the series when compared with standard drug acarbose (IC<sub>50</sub> = 11.29 ± 0.07 and 11.12 ± 0.15 µM, respectively). These derivatives may potentially serve as the lead candidates for the development of new therapeutic representatives. The structure–activity relationship was carried out for all molecules which are mainly based upon the pattern of substituent/s on phenyl rings. Moreover, in silico docking studies were carried out to investigate the active binding mode of selected derivatives with the target enzymes.https://www.mdpi.com/1420-3049/27/20/6921benzimidazolethiosemicarbazonesynthesisalpha-amylasealpha-glucosidasedocking study |
| spellingShingle | Hayat Ullah Shoaib Khan Fazal Rahim Muhammad Taha Rashid Iqbal Maliha Sarfraz Syed Adnan Ali Shah Muhammad Sajid Mohamed F. Awad Awatif Omran Marzough Aziz Albalawi Mahmoud A. Abdelaziz Azza Al Areefy Ibrahim Jafri Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study Molecules benzimidazole thiosemicarbazone synthesis alpha-amylase alpha-glucosidase docking study |
| title | Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study |
| title_full | Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study |
| title_fullStr | Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study |
| title_full_unstemmed | Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study |
| title_short | Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study |
| title_sort | benzimidazole bearing thiosemicarbazone derivatives act as potent α amylase and α glucosidase inhibitors synthesis bioactivity screening and molecular docking study |
| topic | benzimidazole thiosemicarbazone synthesis alpha-amylase alpha-glucosidase docking study |
| url | https://www.mdpi.com/1420-3049/27/20/6921 |
| work_keys_str_mv | AT hayatullah benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT shoaibkhan benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT fazalrahim benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT muhammadtaha benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT rashidiqbal benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT malihasarfraz benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT syedadnanalishah benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT muhammadsajid benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT mohamedfawad benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT awatifomran benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT marzoughazizalbalawi benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT mahmoudaabdelaziz benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT azzaalareefy benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy AT ibrahimjafri benzimidazolebearingthiosemicarbazonederivativesactaspotentaamylaseandaglucosidaseinhibitorssynthesisbioactivityscreeningandmoleculardockingstudy |