Synthesis, Evaluation of New Imidazolidin-4-one and Thiazolidine -4- one compound on Insulin in the Serum of Type 1 Diabetes Albino Rats

Subject Areas : Journal of Chemical Health Risks

Laith G. Atiya ¹ , Omar M. Yahya ² , Salim J. Mohammed ³

1 - Chemistry Department, College of Science, University of Mosul, Mosul, Iraq
2 - 2Department of Biochemistry, College of Medicine, Mosul University, Mosul, Iraq
3 - Department of Chemistry, college of science, university of Mosul, Mosul, Iraq

Received: 2023-08-11 Accepted : 2024-02-26 Published : 2024-05-06

Keywords: 4-(2, 4-di chlorophenoxy) butyric acid, Hydrazide, Hydrazine, Imidazolidine, Thiazolidine, Molecular docking,

Abstract :

This paper includes the synthesis of new imidazolidine-4-one and thiazolidine-4-one derivatives derived from 4-(2,4-dichlorophenoxy) butyric acid (1) by multistep reaction, the first step synthesis ester (2) by the esterification reaction of 4-(2,4-dichlorophenoxy) butyric acid with ethanol in the presence of sulfuric acid. Ester namely ethyl 4-(2,4-dichlorophenoxy) butanoate (2) was converted to the corresponding 4-(2,4-dichloro phenoxy)butane hydrazide (3) by reaction with hydrazine hydrate after those hydrazones (4a-f) derivatives were obtained by the reaction of carboxylic acid hydrazide (3) with various substituted aromatic aldehydes, this hydrazone were used to synthesize some new heterocyclic compounds by the hydrazones (4a-f) with Phenyl Alanine and thioglycolic acid to prepare imidazolidine-4-one(5a-e) and thiazolidine-4-one (6a-d) compounds respectively. The molecular docking study was carried out with the essential enzyme Insulin (PDB 1i144) responsible for Diabetes, suggesting that (4a-e) are the most active derivatives of the series that is responsible for diabetes, for some of the compounds that were prepared in this study. It was found that compounds (4a-e) are the most active derivatives. All newly synthesized compounds in this study were confirmed by physical and spectral (FT-IR, 1H NMR, and 13C NMR) analysis.

References:

1. Katsarou A., Gudbjörnsdottir S., Rawshani A., Dabelea D., Bonifacio E., Anderson B.J., Ark Å., 2017. Type1 diabetes mellitus. Nature reviews Disease Primers. 3(1), 1-17.
2. Williams R., 2015. The economics of diabetes care: a global perspective. International Textbook of Diabetes Mellitus. 1113 - 1124.
3. Flores-Bocanegra L., Pérez-Vásquez A., Torres-Piedra M., Bye R., Linares E., Mata R., 2015. α-Glucosidase inhibitors from Vauquelinia corymbosa. Molecules. 20(8), 15330-15342.
4. Scully T., 2012. Diabetes in numbers. Nature. 485(7398), S2-S3.
5. Mohan V., Anbalagan V.P., 2013. Expanding role of the Madras diabetes research foundation-Indian diabetes risk score in clinical practice. Indian Journal of Endocrinology and Metabolism. 17(1), 31.
6. Kerru N., Gummidi L., Maddila S., Gangu K.K., Jonnalagadda S.B., 2020. A review on recent advances in nitrogen-containing molecules and their biological applications. Molecules. 25(8), 1909.
7. Saleh M.Y., Al-barwari A.S., Ayoob A.I., 2022. Synthesis of Some Novel 1, 8-Naphthyridine Chalcones as Antibacterial Agents. Journal of Nanostructures. 12(3), 598-606.
8. Kumar R.S., Idhayadhulla A., Abdul Nasser A.J., Selvin J., 2010. Synthesis and characterization of new series of imidazolidin-2, 4-dione derivatives and its antimicrobial activity. Oriental Journal of Chemistry. 26, 1425-1430.
9. Kieć-Kononowicz K., Szymańska E., Motyl M., Holzer W., Białecka A., Kasprowic A., 1998. Synthesis, spectral and antimicrobial properties of 5-chloroarylidene aromatic derivatives of imidazoline-4-one. Die Pharmazie. 53(10), 680-684.
10. Ali D., Alarifi S., Chidambaram S.K., Radhakrishnan S.K., Akbar I., 2020. Antimicrobial activity of novel 5-benzylidene-3-(3-phenylallylideneamino) imidazolidine-2, 4-dione derivatives causing clinical pathogens: Synthesis and molecular docking studies. Journal of Infection and Public Health. 13(12), 1951-1960.
11. Godefroi E.F., Platje J.T.J., 1972. DL-1-(. alpha.-Methylbenzyl)-2-methylimidazole-5-carboxylate esters. Synthesis and pharmacological properties. Journal of Medicinal Chemistry. 15(3), 336-337.
12.Kacem Y., Hassine B.B., 2014. Solvent-free synthesis of new chiral 3-phenylamino-3, 5-dihydro-4H-imidazol-4-one derivatives from α-amino acid phenylhydrazides. Heterocycles. 89(1), 197-207.
13. Subtel’na I., Atamanyuk D., Szymańska E., Kieć-Kononowicz K., Zimenkovsky B., Vasylenko O., Gzella A., Lesyk R., 2010. Synthesis of 5-arylidene-2-amino-4-azolones and evaluation of their anticancer activity. Bioorganic & Medicinal Chemistry. 18(14), 5090-5102.
14. Alghamdi S.S., Suliman R.S., Almutairi K., Kahtani K., Aljatli D., 2021. Imidazole as a promising medicinal scaffold: Current status and future direction. Drug Design, Development and Therapy. 3289-3312.
15. Arkan Majhool A., Yakdhan Saleh M., Obaid Aldulaimi A.K., Mahmood Saeed S., Hassan S.M., El-Shehry M.F., Mohamed Awad S., Syed Abdul Azziz S.S., 2023. Synthesis of New Azo Dyes of Uracil via Ecofriendly Method and Evaluation for the Breast, Liver and Lung Cancer Cells In vitro. Chemical Review and Letters. 6(4), 442-448.
16. Arif I.A., Ahamed A., Kumar R.S., Idhayadhulla A., Manilal A., 2019. Cytotoxic, larvicidal, nematicidal, and antifeedant activities of piperidin-connected 2-thioxoimidazolidin-4-one derivatives. Saudi Journal of Biological Sciences. 26(4), 673-680.
17. Rodriguez F., Rozas I., Ortega J.E., Erdozain A.M., Meana J.J., Callado L.F., 2009. Guanidine and 2-aminoimidazoline aromatic derivatives as α2-adrenoceptor ligands: searching for structure− activity relationships. Journal of Medicinal Chemistry. 52(3), 601-609.
18. Ergenç N., Çapan G., Günay N.S., Özkirimli S., Güngör M., Özbey S., Kendi E., 1999. Synthesis and hypnotic activity of new 4‐thiazolidinone and 2‐thioxo‐4, 5‐imidazolidinedione derivatives. Archiv der Pharmazie: An International Journal Pharmaceutical and Medicinal Chemistry. 332(10), 343-347.
19. Ravichandran V., Kumar B.P., Sankar S., Agrawal R.K., 2009. Predicting anti-HIV activity of 1, 3, 4-thiazolidinone derivatives: 3D-QSAR approach. European Journal of Medicinal Chemistry. 44(3), 1180-1187.
20. Omar K., Geronikaki A., Zoumpoulakis P., Camoutsis C., Soković M., Ćirić A., Glamočlija J., 2010. Novel 4-thiazolidinone derivatives as potential antifungal and antibacterial drugs. Bioorganic & Medicinal Chemistry. 18(1), 426-432.
21. Verma A., Saraf S.K., 2008. 4-Thiazolidinone–A biologically active scaffold. European Journal of Medicinal Chemistry. 43(5), 897-905.
22. Tratrat C., Petrou A., Geronikaki A., Ivanov M., Kostić M., Soković M., Vizirianakis I.S., Theodoroula N.F., Haroun M., 2022. Thiazolidin-4-ones as potential antimicrobial agents: experimental and in silico evaluation. Molecules. 27(6), 1930.
23. Sabeeh Hasan I., Yakdhan Saleh M., Aldulaimi A. K., Saeed S. M., Adil M., Adhab A. H., 2024. A Review: Metal-Organic Frameworks Electrochemical Biosensors for Bioorganic Materials Detection. Analytical and Bioanalytical Electrochemistry. 16(1), 100-125.
24. Hassan S.A., Ziwar J.B., Muhammed Aziz D., Abdullah M.N., 2024. Sonochemical synthesis of New Thiazolidin-4-one derivatives as potent anticancer and antimicrobial agents with Docking design, and Energy gap estimation. Journal of Molecular Structure. 1301, 137282.
25. Sharma A., Sharma D., Saini N., Sharma S.V., Thakur V.K., Goyal R.K., Sharma P.C., 2023. Recent advances in synthetic strategies and SAR of thiazolidin-4-one containing molecules in cancer therapeutics. Cancer and Metastasis Reviews. 1-43.
26. Roszczenko P., Holota S., Szewczyk O.K., Dudchak R., Bielawski K., Bielawska A., Lesyk, R., 2022. 4-Thiazolidinone-bearing hybrid molecules in anticancer drug design. International Journal of Molecular Sciences. 23(21), 13135.
27. Havrylyuk D., Zimenkovsky B., Lesyk R., 2009. Synthesis and anticancer activity of novel nonfused bicyclic thiazolidinone derivatives. Phosphorus, Sulfur, and Silicon. 184(3), 638-650.
28. Tanabe Y., Suzukamo G., Komuro Y., Imanishi N., Morooka S., Enomoto M., Kojima A., Sanemitsu Y., Mizutani M., 1991. Structure-activity relationship of optically active 2-(3-pyridyl) thiazolidin-4-ones as a PAF antagonists. Tetrahedron Letters. 32(3), 379-382.
29. Kato T., Ozaki T., Ohi N., 1999. Improved synthetic methods of CP-060S, a novel cardioprotective drug. Tetrahedron: Asymmetry. 10(20), 3963-3968.
30. Adachi Y., Suzuki Y., Homma N., Fukazawa M., Tamura K., Nishie I., Kuromaru O., 1999. The anti-ischemic effects of CP-060S during pacing-induced ischemia in anesthetized dogs. European Journal of Pharmacology. 367(2-3), 267-273.
31. Hara A., Suzuki T., Hashizume H., Shishido N., Nakamura M., Ushikubi F., Abiko Y., 1999. Effects of CP-060S, a novel Ca2+ channel blocker, on oxidative stress in cultured cardiac myocytes. European Journal of Pharmacology. 385(1), 81-88.
32. Ottaná R., Mazzon E., Dugo L., Monforte F., Maccari R., Sautebin L., Cuzzocrea S., 2002. Modeling and biological evaluation of 3, 3′-(1, 2-ethanediyl) bis [2-(4-methoxyphenyl)-thiazolidin-4-one], a new synthetic cyclooxygenase-2 inhibitor. European Journal of Pharmacology. 448(1), 71-80.
33. Saleh M., Sadeek G., Saied S., 2023. Preparation and characterization of a dual acidic Ionic Liquid functionalized Graphene Oxide nanosheets as a Heterogeneous Catalyst for the Synthesis of pyrimido[4,5-b] quinolines in water. Iranian Journal of Catalysis. 13(4), 499-516.
34. Nimbalkar U.D., Seijas J.A., Borkute R., Damale M.G., Sangshetti J.N., Sarkar D., Nikalje A.P.G., 2018. Ultrasound Assisted Synthesis of 4-(Benzyloxy)-N-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl) benzamide as challenging anti-tubercular scaffold. Molecules. 23(8), 1945.
35. Raauf A.M., 2019. Synthesis, characterization and antibacterial activity of new derivatives of imidazolidine having sulfamethoxazole moiety. Al Mustansiriyah Journal of Pharmaceutical Sciences. 19(4), 217-238.
36. Popiołek Ł., Stefańska J., Kiełczykowska M., Musik I., Biernasiuk A., Malm A., Wujec M., 2016. Synthesis, Dissociation Constants, and Antimicrobial Activity of Novel 2, 3‐Disubstituted‐1, 3‐thiazolidin‐4‐one Derivatives. Journal of Heterocyclic Chemistry. 53(2), 393-402.
37. Hussain F., Khan Z., Jan M. S., Ahmad S., Ahmad A., Rashid U., Sadiq A., 2019. Synthesis, in-vitro α-glucosidase inhibition, antioxidant, in-vivo antidiabetic and molecular docking studies of pyrrolidine-2, 5-dione and thiazolidine-2, 4-dione derivatives. Bioorganic chemistry. 91, 103.