Synthesis and Structure-activity Relationship Studies of Benzimidazole-thioquinoline Derivatives As α-glucosidase Inhibitors

Overview

Journal Sci Rep

Specialty Science

Date 2023 Mar 17

PMID 36928433

Authors

Sara Moghadam Farid

Milad Noori

Mohammad Nazari Montazer

Minoo Khalili Ghomi

Marjan Mollazadeh

Navid Dastyafteh

Cambyz Irajie

Kamiar Zomorodian

Seyedeh Sara Mirfazli

Somayeh Mojtabavi

Mohammad Ali Faramarzi

Bagher Larijani

Aida Iraji

Mohammad Mahdavi

Affiliations

Soon will be listed here.

Abstract

In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC value of 28.0 ± 0.6 µM compared to acarbose as the positive control with an IC value of 750.0 µM. The kinetic study showed a competitive inhibition pattern against α-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential α-glucosidase inhibitors.

Citing Articles

Substituted piperazine conjugated to quinoline-thiosemicarbazide as potent α-glucosidase inhibitors to target hyperglycemia.

Ghasemi M, Mahdavi M, Dehghan M, Eftekharian M, Mojtabavi S, Faramarzi M Sci Rep. 2025; 15(1):1871.

PMID: 39805968 PMC: 11730591. DOI: 10.1038/s41598-024-83917-z.

Quinoline-thiosemicarbazone-1,2,3-triazole-acetamide derivatives as new potent α-glucosidase inhibitors.

Khademian A, Halimi M, Azarbad R, Alaedini A, Noori M, Dastyafteh N Sci Rep. 2024; 14(1):30876.

PMID: 39730503 PMC: 11680592. DOI: 10.1038/s41598-024-81668-5.

Novel bis-benzimidazole-triazole hybrids: anticancer study, in silico approaches, and mechanistic investigation.

Soliman M, Ahmed H, Eltamany E, Boraei A, Aljuhani A, Salama S Future Med Chem. 2024; 17(1):93-107.

PMID: 39670306 PMC: 11702989. DOI: 10.1080/17568919.2024.2437980.

Synthesis, α-glucosidase inhibitory activity, and molecular dynamic simulation of 6-chloro-2-methoxyacridine linked to triazole derivatives.

Asadi M, Ahangari M, Iraji A, Azizian H, Nokhbehzaim A, Bahadorikhalili S Sci Rep. 2024; 14(1):17338.

PMID: 39069559 PMC: 11284203. DOI: 10.1038/s41598-024-68176-2.

Coumarin linked to 2-phenylbenzimidazole derivatives as potent α-glucosidase inhibitors.

Ganjeh M, Mazlomifar A, Shahvelayti A, Moghaddam S Sci Rep. 2024; 14(1):7408.

PMID: 38548784 PMC: 10978946. DOI: 10.1038/s41598-024-57673-z.

References

Ali S, Mohamed Awad S, Said A, Mahgoub S, Taha H, Ahmed N . Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors. J Enzyme Inhib Med Chem. 2020; 35(1):847-863. PMC: 7170299. DOI: 10.1080/14756366.2020.1742116. View

Naureen S, Chaudhry F, Munawar M, Ashraf M, Hamid S, Khan M . Biological evaluation of new imidazole derivatives tethered with indole moiety as potent α-glucosidase inhibitors. Bioorg Chem. 2017; 76:365-369. DOI: 10.1016/j.bioorg.2017.12.014. View

Karami M, Hasaninejad A, Mahdavi H, Iraji A, Mojtabavi S, Faramarzi M . One-pot multi-component synthesis of novel chromeno[4,3-b]pyrrol-3-yl derivatives as alpha-glucosidase inhibitors. Mol Divers. 2021; 26(5):2393-2405. PMC: 8544188. DOI: 10.1007/s11030-021-10337-w. View

Liu S, Hao H, Bian Y, Ge Y, Lu S, Xie H . Discovery of New α-Glucosidase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation. Front Chem. 2021; 9:639279. PMC: 7982526. DOI: 10.3389/fchem.2021.639279. View

Zarenezhad E, Nazari Montazer M, Tabatabaee M, Irajie C, Iraji A . New solid phase methodology for the synthesis of biscoumarin derivatives: experimental and in silico approaches. BMC Chem. 2022; 16(1):53. PMC: 9275028. DOI: 10.1186/s13065-022-00844-8. View

Pires D, Blundell T, Ascher D . pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. J Med Chem. 2015; 58(9):4066-72. PMC: 4434528. DOI: 10.1021/acs.jmedchem.5b00104. View

Iraji A, Shareghi-Brojeni D, Mojtabavi S, Faramarzi M, Akbarzadeh T, Saeedi M . Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors. Sci Rep. 2022; 12(1):8647. PMC: 9125976. DOI: 10.1038/s41598-022-11771-y. View

Sohrabi M, Binaeizadeh M, Iraji A, Larijani B, Saeedi M, Mahdavi M . A review on α-glucosidase inhibitory activity of first row transition metal complexes: a futuristic strategy for treatment of type 2 diabetes. RSC Adv. 2022; 12(19):12011-12052. PMC: 9020348. DOI: 10.1039/d2ra00067a. View

Pedrood K, Rezaei Z, Khavaninzadeh K, Larijani B, Iraji A, Hosseini S . Design, synthesis, and molecular docking studies of diphenylquinoxaline-6-carbohydrazide hybrids as potent α-glucosidase inhibitors. BMC Chem. 2022; 16(1):57. PMC: 9341091. DOI: 10.1186/s13065-022-00848-4. View

10.

Daina A, Michielin O, Zoete V . SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017; 7:42717. PMC: 5335600. DOI: 10.1038/srep42717. View

11.

Al-Ishaq R, Abotaleb M, Kubatka P, Kajo K, Busselberg D . Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels. Biomolecules. 2019; 9(9). PMC: 6769509. DOI: 10.3390/biom9090430. View

12.

Yan J, Zhang G, Pan J, Wang Y . α-Glucosidase inhibition by luteolin: kinetics, interaction and molecular docking. Int J Biol Macromol. 2013; 64:213-23. DOI: 10.1016/j.ijbiomac.2013.12.007. View

13.

Forster J, Duis J, Butler M . Pharmacogenetic Testing of Cytochrome P450 Drug Metabolizing Enzymes in a Case Series of Patients with Prader-Willi Syndrome. Genes (Basel). 2021; 12(2). PMC: 7912498. DOI: 10.3390/genes12020152. View

14.

Li Y, Zhang J, Xie H, Ge Y, Wang K, Song Z . Discovery of new 2-phenyl-1H-benzo[d]imidazole core-based potent α-glucosidase inhibitors: Synthesis, kinetic study, molecular docking, and in vivo anti-hyperglycemic evaluation. Bioorg Chem. 2021; 117:105423. DOI: 10.1016/j.bioorg.2021.105423. View

15.

Khan K, Rahim F, Wadood A, Kosar N, Taha M, Lalani S . Synthesis and molecular docking studies of potent α-glucosidase inhibitors based on biscoumarin skeleton. Eur J Med Chem. 2014; 81:245-52. DOI: 10.1016/j.ejmech.2014.05.010. View

16.

Weeda E, Muraoka A, Brock M, Cannon J . Medication adherence to injectable glucagon-like peptide-1 (GLP-1) receptor agonists dosed once weekly vs once daily in patients with type 2 diabetes: A meta-analysis. Int J Clin Pract. 2021; 75(9):e14060. DOI: 10.1111/ijcp.14060. View

17.

Hermans M, Kroos M, Van Beeumen J, Oostra B, Reuser A . Human lysosomal alpha-glucosidase. Characterization of the catalytic site. J Biol Chem. 1991; 266(21):13507-12. View

18.

Zhou Y, Ingelman-Sundberg M, Lauschke V . Worldwide Distribution of Cytochrome P450 Alleles: A Meta-analysis of Population-scale Sequencing Projects. Clin Pharmacol Ther. 2017; 102(4):688-700. PMC: 5600063. DOI: 10.1002/cpt.690. View

19.

Zawawi N, Taha M, Ahmat N, Wadood A, Ismail N, Rahim F . Benzimidazole derivatives as new α-glucosidase inhibitors and in silico studies. Bioorg Chem. 2015; 64:29-36. DOI: 10.1016/j.bioorg.2015.11.006. View

20.

Taha M, Ismail N, Imran S, Mohamad M, Wadood A, Rahim F . Synthesis, α-glucosidase inhibitory, cytotoxicity and docking studies of 2-aryl-7-methylbenzimidazoles. Bioorg Chem. 2016; 65:100-9. DOI: 10.1016/j.bioorg.2016.02.004. View