Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study
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
Affiliations
Hayat Ullah
Department of Chemistry, University of Okara, Okara 56300, Pakistan
Shoaib Khan
Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
Fazal Rahim
Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
Muhammad Taha
Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
Rashid Iqbal
Department of Agronomy, Faculty of Agriculture and Environment, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
Maliha Sarfraz
Department of Zoology, Wildlife and Fisheries, University of Agriculture Faisalabad, Sub-Campus Toba Tek Singh, Punjab 36050, Pakistan
Syed Adnan Ali Shah
Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam, Selangor 42300, Malaysia
Muhammad Sajid
Department of Biochemistry, Hazara University, Mansehra 21120, Pakistan
Mohamed F. Awad
Department of Biology, College of Science, Taif University, Taif 21944, Saudi Arabia
Awatif Omran
Department of Biochemistry, College of Science, University of Tabuk, Tabuk 71491, Saudi Arabia
Marzough Aziz Albalawi
Department of Chemistry, Alwajh College, University of Tabuk, Tabuk 71491, Saudi Arabia
Mahmoud A. Abdelaziz
Department of Chemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia
Azza Al Areefy
Clinical Nutrition Department, Applied Medical Science Collage, Jazan University, Jazan 45142, Saudi Arabia
Ibrahim Jafri
Department of Biotechnology, Faculty of Sciences, Taif University, Taif 21944, Saudi Arabia
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 (7–21) 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 19 (IC50 = 1.30 ± 0.20 µM and 1.20 ± 0.20 µM) and 20 (IC50 = 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 (IC50 = 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.
