Synthesis,biological evaluation and molecular docking studies of novel benzimidazole derivatives
Affiliation:
1. Synthetic Organic and Medicinal Chemistry Laboratory, Department of Chemistry, Punjabi University, Patiala 147002, Punjab, India;2. Department of Basic and Applied Sciences, Punjabi University, Patiala 147002, Punjab, India;3. Department of Botany, Punjabi University, Patiala 147002, Punjab, India;1. Department of Chemistry, School of Natural Sciences, Shiv Nadar University, Dadri, Chithera, Gautam Budh Nagar, Uttar Pradesh 201314, India;2. Institute of Science and Technology (Autonomous), Jawaharlal Nehru Technological University, Kukatpally, Hyderabad, Telangana 500085, India;3. Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Dadri, Chithera, Gautam Budh Nagar, Uttar Pradesh 201314, India;1. Department of Chemistry and Industrial Chemistry, University of Genoa, Via Dodecaneso 31, I-16146 Genoa, Italy;2. Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari Aldo Moro, via E. Orabona 4, 70126 Bari, Italy;3. Department of Pharmacy – Drug Sciences, University of Bari Aldo Moro, via E. Orabona 4, 70126 Bari, Italy;1. Chemistry Department, College of Science, Qassim University, Qassim, Buraydah, Saudi Arabia;2. Chemistry Department, Faculty of Science, Mansoura University, 35516 Mansoura, Egypt;3. Hormones Department, Medical Research Division, National Research Centre, Dokki, Giza, 12622, Egypt;4. Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Giza 12622, Egypt;1. Jinnah University for Women, 5-C, Nazimabad, Karachi 74600, Pakistan;2. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;3. Deparment of Chemistry, Karakoram International University, Gilgit, Pakistan;4. Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;5. Department of Biochemistry, Shankar Campus, Abdul Wali Khan University, Mardan, Khyber Pukhtoonkhwa, Pakistan;6. PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan;7. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia;8. Faculty of Applied Science Universiti Teknologi MARA, Shah Alam 40450, Selangor D. E., Malaysia;1. Department of Chemistry, Faculty of Art and Sciences, Recep Tayyip Erdogan University, 53100 Rize, Turkey;2. Vocational School of Technical Studies, Department of Chemistry and Chemical Processing Technology, Recep Tayyip Erdogan University, 53100 Rize, Turkey;3. Department of Nutrition and Dietetics, Faculty of Health Sciences, Karadeniz Technical University, 61080 Trabzon, Turkey
Abstract:
A novel series of N-substituted-benzimidazolyl linked para substituted benzylidene based molecules containing three pharmacologically potent hydrogen bonding parts namely; 2,4-thiazolidinedione (TZD: a 2,4-dicarbonyl), diethyl malonate (DEM: a 1,3-diester and an isooxazolidinedione analog) and methyl acetoacetate (MAA: a β-ketoester) (6a–11b) were synthesized and evaluated for in vitro α-glucosidase inhibition. The structure of the novel synthesized compounds was confirmed through the spectral studies (LC–MS, 1H NMR, 13C NMR, FT-IR). Comparative evaluation of these compounds revealed that the compound 9b showed maximum inhibitory potential against α-amylase and α-glucosidase giving an IC50 value of 0.54 ± 0.01 μM. Furthermore, binding affinities in terms of G score values and hydrogen bond interactions between all the synthesized compounds and the AA residues in the active site of the protein (PDB code: 3TOP) to that of Acarbose (standard drug) were explored with the help of molecular docking studies. Compound 9b was considered as promising candidate of this series.
