Imidazopyridine-Based Thiazole Derivatives As Potential Antidiabetic Agents: Synthesis, In Vitro Bioactivity, and In Silico Molecular Modeling Approach

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2023 Sep 28

PMID 37765096

Authors

Rafaqat Hussain

Wajid Rehman

Shoaib Khan

Aneela Maalik

Mohamed Hefnawy

Ashwag S Alanazi

Yousaf Khan

Liaqat Rasheed

Affiliations

Soon will be listed here.

Abstract

A new series of thiazole derivatives () incorporating imidazopyridine moiety was synthesized and assessed for their in vitro potential α-glucosidase potency using acarbose as a reference drug. The obtained results suggested that compounds (docking score = -13.45), (docking score = -12.87), (docking score = -12.15), and (docking score = -11.25) remarkably showed superior activity against the targeted α-glucosidase enzyme, with IC values of 5.57 ± 3.45, 8.85 ± 2.18, 7.16 ± 1.40, and 10.48 ± 2.20, respectively. Upon further investigation of the binding mode of the interactions by the most active scaffolds with the α-glucosidase active sites, the docking analysis was accomplished in order to explore the active cavity of the α-glucosidase enzyme. The interpretation of the results showed clearly that scaffolds and emerged as the most potent α-glucosidase inhibitors, with promising excellent binding interactions with the active site of the α-glucosidase enzyme. Furthermore, utilizing a variety of spectroscopic methods, such as H-NMR, C-NMR, and HREI-MS, the precise structures of the synthesized scaffolds were determined.

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References

Hemaida A, Hassan G, Maarouf A, Joubert J, El-Emam A . Synthesis and Biological Evaluation of Thiazole-Based Derivatives as Potential Acetylcholinesterase Inhibitors. ACS Omega. 2021; 6(29):19202-19211. PMC: 8320107. DOI: 10.1021/acsomega.1c02549. View

Prabhakar P, Doble M . Mechanism of action of natural products used in the treatment of diabetes mellitus. Chin J Integr Med. 2011; 17(8):563-74. DOI: 10.1007/s11655-011-0810-3. View

Ayati A, Emami S, Moghimi S, Foroumadi A . Thiazole in the targeted anticancer drug discovery. Future Med Chem. 2019; 11(15):1929-1952. DOI: 10.4155/fmc-2018-0416. View

Bell D . Type 2 diabetes mellitus: what is the optimal treatment regimen?. Am J Med. 2004; 116 Suppl 5A:23S-29S. DOI: 10.1016/j.amjmed.2003.10.017. View

. 5. Prevention or Delay of Type 2 Diabetes: . Diabetes Care. 2017; 41(Suppl 1):S51-S54. DOI: 10.2337/dc18-S005. View

Hussain R, Ullah H, Rahim F, Sarfraz M, Taha M, Iqbal R . Multipotent Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease: Synthesis, Biological Analysis and Molecular Docking Study of Benzimidazole-Based Thiazole Derivatives. Molecules. 2022; 27(18). PMC: 9504419. DOI: 10.3390/molecules27186087. View

Santana T, de Oliveira Barbosa M, de Moraes Gomes P, Nascimento da Cruz A, da Silva T, Lima Leite A . Synthesis, anticancer activity and mechanism of action of new thiazole derivatives. Eur J Med Chem. 2018; 144:874-886. DOI: 10.1016/j.ejmech.2017.12.040. View

Khan S, Iqbal S, Shah M, Rehman W, Hussain R, Rasheed L . Synthesis, In Vitro Anti-Microbial Analysis and Molecular Docking Study of Aliphatic Hydrazide-Based Benzene Sulphonamide Derivatives as Potent Inhibitors of α-Glucosidase and Urease. Molecules. 2022; 27(20). PMC: 9609496. DOI: 10.3390/molecules27207129. View

Kalkhambkar R, Kulkarni G, Shivkumar H, Rao R . Synthesis of novel triheterocyclic thiazoles as anti-inflammatory and analgesic agents. Eur J Med Chem. 2007; 42(10):1272-6. DOI: 10.1016/j.ejmech.2007.01.023. View

10.

Rostom S, El-Ashmawy I, Abd El Razik H, Badr M, Ashour H . Design and synthesis of some thiazolyl and thiadiazolyl derivatives of antipyrine as potential non-acidic anti-inflammatory, analgesic and antimicrobial agents. Bioorg Med Chem. 2008; 17(2):882-95. DOI: 10.1016/j.bmc.2008.11.035. View

11.

Luzina E, Popov A . Synthesis and anticancer activity of N-bis(trifluoromethyl)alkyl-N'-thiazolyl and N-bis(trifluoromethyl)alkyl-N'-benzothiazolyl ureas. Eur J Med Chem. 2009; 44(12):4944-53. DOI: 10.1016/j.ejmech.2009.08.007. View

12.

Khan S, Iqbal S, Rahim F, Shah M, Hussain R, Alrbyawi H . New Biologically Hybrid Pharmacophore Thiazolidinone-Based Indole Derivatives: Synthesis, In Vitro Αlpha-Amylase and Αlpha-Glucosidase Along with Molecular Docking Investigations. Molecules. 2022; 27(19). PMC: 9571711. DOI: 10.3390/molecules27196564. View

13.

Rahim F, Javed M, Ullah H, Wadood A, Taha M, Ashraf M . Synthesis, molecular docking, acetylcholinesterase and butyrylcholinesterase inhibitory potential of thiazole analogs as new inhibitors for Alzheimer disease. Bioorg Chem. 2015; 62:106-16. DOI: 10.1016/j.bioorg.2015.08.002. View

14.

Haroun M, Tratrat C, Tsolaki E, Geronikaki A . Thiazole-Based Thiazolidinones as Potent Antimicrobial Agents. Design, Synthesis and Biological Evaluation. Comb Chem High Throughput Screen. 2015; 19(1):51-7. DOI: 10.2174/1386207319666151203002348. View

15.

Park S, Kim H, Son J, Um K, Lee S, Baek Y . Synthesis of Imidazopyridines via Copper-Catalyzed, Formal Aza-[3 + 2] Cycloaddition Reaction of Pyridine Derivatives with α-Diazo Oxime Ethers. J Org Chem. 2017; 82(19):10209-10218. DOI: 10.1021/acs.joc.7b01714. View

16.

Britschgi M, von Greyerz S, Burkhart C, Pichler W . Molecular aspects of drug recognition by specific T cells. Curr Drug Targets. 2003; 4(1):1-11. DOI: 10.2174/1389450033347082. View

17.

Belohlavek D, Malfertheiner P . The effect of zolimidine, imidazopyridine-derivate, on the duodenal ulcer healing. Scand J Gastroenterol Suppl. 1979; 54:44. View

18.

Chevallet P, Kilic F, Erol K . Synthesis of some thiazolyl-pyrazoline derivatives and preliminary investigation of their hypotensive activity. Eur J Med Chem. 2000; 35(6):635-41. DOI: 10.1016/s0223-5234(00)00152-5. View

19.

Xu X, Wang G, Zhou T, Chen L, Chen J, Shen X . Novel approaches to drug discovery for the treatment of type 2 diabetes. Expert Opin Drug Discov. 2014; 9(9):1047-58. DOI: 10.1517/17460441.2014.941352. View

20.

Javid M, Rahim F, Taha M, Rehman H, Nawaz M, Wadood A . Synthesis, in vitro α-glucosidase inhibitory potential and molecular docking study of thiadiazole analogs. Bioorg Chem. 2018; 78:201-209. DOI: 10.1016/j.bioorg.2018.03.022. View