Статья

Synthesis of Novel Benzimidazole-Based Thiazole Derivatives as Multipotent Inhibitors of α-Amylase and α-Glucosidase: In Vitro Evaluation along with Molecular Docking Study

Rafaqat HussainDepartment of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, PakistanShahid IqbalDepartment of Chemistry, School of Natural Sciences (SNS), National University of Science and Technology (NUST), H-12, Islamabad 46000, PakistanMazloom ShahDepartment of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad 22500, PakistanWajid RehmanDepartment of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, PakistanShoaib KhanDepartment of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, PakistanLiaqat RasheedDepartment of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, PakistanFazal RahimDepartment of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, PakistanAyed A. DeraDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61413, Saudi ArabiaSana KehiliAdham University College, Umm Al-Qura University, Makkah 21955, Saudi ArabiaEslam B. ElkaeedDepartment of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh 13713, Saudi ArabiaNasser S. AwwadChemistry Department, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi ArabiaMajed A. BajaberChemistry Department, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi ArabiaMohammed Issa AlahmdiDepartment of Chemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi ArabiaHamad AlrbyawiPharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, Medina 42353, Saudi ArabiaHashem O. AlsaabDepartment of Pharmaceutics and Pharmaceutical Technology, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia

2022en

ABI

Аннотация

In this study, hybrid analogs of benzimidazole containing a thiazole moiety (1–17) were afforded and then tested for their ability to inhibit α-amylase and α-glucosidase when compared to acarbose as a standard drug. The recently available analogs showed a wide variety of inhibitory potentials that ranged between 1.31 ± 0.05 and 38.60 ± 0.70 µM (against α-amylase) and between 2.71 ± 0.10 and 42.31 ± 0.70 µM (against α-glucosidase) under the positive control of acarbose (IC50 = 10.30 ± 0.20 µM against α-amylase) (IC50 = 9.80 ± 0.20 µM against α-glucosidase). A structure–activity relationship (SAR) study was carried out for all analogs based on substitution patterns around both rings B and C respectively. It was concluded from the SAR study that analogs bearing either substituent(s) of smaller size (−F and Cl) or substituent(s) capable of forming hydrogen bonding (−OH) with the catalytic residues of targeted enzymes enhanced the inhibitory potentials. Therefore, analogs 2 (bearing meta-fluoro substitution), 3 (having para-fluoro substitution) and 4 (with ortho-fluoro group) showed enhanced potency when evaluated against standard acarbose drug with IC50 values of 4.10 ± 0.10, 1.30 ± 0.05 and 1.90 ± 0.10 (against α-amylase) and 5.60 ± 0.10, 2.70 ± 0.10 and 2.90 ± 0.10 µM (against α-glucosidase), correspondingly. On the other hand, analogs bearing substituent(s) of either a bulky nature (−Br) or that are incapable of forming hydrogen bonds (−CH3) were found to lower the inhibitory potentials. In order to investigate the binding sites for synthetic analogs and how they interact with the active areas of both targeted enzymes, molecular docking studies were also conducted on the potent analogs. The results showed that these analogs adopted many important interactions with the active areas of enzymes. The precise structure of the newly synthesized compounds was confirmed using several spectroscopic techniques as NMR and HREI-MS.

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Идентификаторы

DOI: 10.3390/molecules27196457

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