Spectrophotometric Determination of Methyldopa and Levodopa by Oxidative Coupling Reactions using the synthesis reagent (2-amino-5-(para-aminophenyl)-1,3,4-thiadiazole) and Investigation of Biological Activity

Subject Areas : Journal of Chemical Health Risks

Doaa Ezaldeen Al-Rashidi ¹ (Department of Chemistry, College of Education for Girls, University of Mosul, Mosul – Iraq.)
Mohammed S. Al-Enizzi ² (Department of Chemistry, college of science for girls, Mosul university, Mosul, Iraq)
Mohanad Y. Saleh ³ (University of Mosul, College of Education for pure Science, Department of Chemistry)

Received: 2023-07-25 Accepted : 2024-02-19 Published : 2024-05-06

Keywords: Oxidative coupling, Spectral estimation, Thiadiazol, Methyldopa, Levo-dopa,

Abstract :

Based on oxidative coupling reactions utilizing the synthesized organic reagent 2-amino-5-(para-aminophenyl)-1,3,4-thiadiazole in acidic media, and with potassium dichromate as an oxidizing agent, a spectrophotometric method has been established for determining methyldopa and levodopa. For these drugs, the resultant complex exhibits peak absorption at 401.5 nm and 415 nm, respectively. The method adheres to Beer's law in the ranges of 1-55 µg ml-1 and 2.5-170 µg ml-1, with molar absorption coefficients of 0.24 x 104 and 0.116 x 104 L mol-1 cm-1, respectively. The quantification limit (LOQ) is set at 1.5769 µg ml-1 for methyldopa and 3.0616 µg ml-1 for levodopa, yielding recovery rates of 100.14% and 100.34%, and relative standard deviation rates of 2.748% and 0.779%. The nature of the resulting complex was examined using the continuous variation method (Job's method) and molar ratios, revealing a 1:2 ratio (reagent to drug compound) for both drugs. This method has been successfully applied to pharmaceutical formulations.

References:

1. Aljamali N.M., 2014. Review in cyclic compounds with heteroatom. Asian Journal of Research in Chemistry. 7(11), 975-1006
2. Onkol T., Cakir B., Sahin M. F., Yildirim E. N. G. İ. N., Erol K., 2004. Synthesis and Antinociceptive Activity of 2-[(2-Oxobenzothiazolin-3-yl) methyl]-5-aminoalkyl/aryl-1, 3, 4-thiadiazole. Turkish Journal of Chemistry. 28(4), 461-468.‏
3. Li Y., Geng J., Liu Y., Yu S., Zhao G., 2013. Thiadiazole—A promising structure in medicinal chemistry. Chem Med Chem. 8(1), 27-41.
4.Foroumadi A., Mirzaei M., Shafiee A., 2001. Antituberculosis agents II. Evaluation of in vitro antituberculosis activity and cytotoxicity of some 2-(1-methyl-5-nitro-2-imidazolyl)-1, 3, 4-thiadiazole derivatives. Il Farmaco. 56(8), 621-623.‏
5. Grynberg N., Santos A. C., Echevarria A., 1997. Synthesis and in vivo antitumor activity of new heterocyclic derivatives of the 1, 3, 4-thiadiazolium-2-aminide class. Anti-Cancer Drugs. 8(1), 88-91.‏
6. Rusu A., Moga I.M., Uncu L., Hancu G., 2023. The Role of Five-Membered Heterocycles in the Molecular Structure of Antibacterial Drugs Used in Therapy. Pharmaceutics. 15(11), 2554.
7. Sadeek G.T., Saeed Z.F., Saleh M.Y., 2023. Synthesis and Pharmacological Profile of Hydrazide Compounds. Research Journal of Pharmacy and Technology. 16(2), 975-982.‏
8. Hamdoon A.M., Saleh M.Y., Saied S.M., 2022. Synthesis & Biological Evaluation of Novel Series of Benzo [f] indazole Derivatives. Egyptian Journal of Chemistry. 65(11), 305-312.
9. 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.‏
10. Saied S.M., Saleh M.Y., Hamdoon A.M., 2022. Multicomponent Synthesis of Tetrahydrobenzo [a] xanthene and Tetrahydrobenzo [a] acridine Derivatives using Sulfonated Multi-Walled Carbon Nanotubes as Heterogeneous Nanocatalysts. Iranian Journal of Catalysis. 12(2), 189-205.‏
11. Saleh A., Saleh M.Y., 2022. Synthesis of heterocyclic compounds by cyclization of Schiff bases prepared from capric acid hydrazide and study of biological activity. Egyptian Journal of Chemistry. 65(12), 783-792.‏
12. Ali A.H., Saleh M.Y., Owaid K.A., 2023. Mild Synthesis, Characterization, and Application of some Polythioester Polymers Catalyzed by Cetrimide Ionic Liquid as a Green and Eco-Friendly Phase-Transfer Catalyst. Iranian Journal of Catalysis. 13(1), 73-83.
13. Saleh M.Y., Abdelzaher M., Ali A.H., Owaid K.A., 2023. Synthesis and Characterization of some new Heterocyclic Polymer Compounds from Benzo [1, 2-d: 4, 5-d] bis (thiazole)-2, 6-diamine and [6, 6'-Bibenzo [d] thiazole]-2, 2'-diamine. Rafidain Journal of Science. 32(4), 57-69.
14. Molla Ali Akbari S., Rabbani M., Sharifzadeh M., Hosseini-Sharifabad A., 2017. Effects of Maternal Alpha Methyldopa Administration on Memory of Rat Offspring during Growing Age. Iranian Journal of Toxicology. 11(1), 43-47.‏
15. AL-ghanam D.N.A., AL-Enizzi M.S.S., 2022. Spectrophotometric determination of methyldopa by oxidative coupling reactions using 2, 4-dinitrophenylhydrazine reagent. Tikrit Journal of Pure Science. 27(5), 16-22.‏
16. Mah G.T., Tejani A.M., Musini V.M., 2009. Methyldopa for primary hypertension. Cochrane Database of Systematic Reviews.2009 (4), CD003893.
17. Al-Abachi M. Q., Al-Da'amy M. A., 2005. Spectrophotometric determination of catechol amine drugs in pharmaceutical preparations via oxidative coupling reaction with 3-amino pyridine and sodium periodate. National Journal. 18, 234.‏
18. Humedyi. T., Salman S.A., Hashim K.K., 2020. Spectrophotometric Determination of Methyldopa With 2, 6-Diaminopyridine Reagent Using Oxidative Coupling Reaction. Journal of Engineering Science and Technology. 15(3), 1824-1839.‏
19. 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.
20. Gadkariem E.A., Ibrahim K.E.E., Kamil N.A.A., Haga M.E.M., El-Obeid H.A., 2009. A new spectrophotometric method for the determination of methyldopa. Saudi Pharmaceutical Journal. 17(4), 289-293.‏
21. AbdulSattar J.A., 2014. Exploiting the diazotization reaction of 4-minoacetophenone for Methyldopa determination. Baghdad Science Journal. 11(1), 139-146.‏
22. Jalalvand A.R., 2022. Engagement of chemometrics and analytical electrochemistry for clinical purposes: A review. Chemometrics and Intelligent Laboratory Systems. 227, 104612.
23. F Hussein A., A AL-Da M., H AL-Fatlawy M., 2013. Spectrophotometric determination of Levo-dopa in pharmaceutical preparation via oxidative coupling organic reaction. Karbala Journal of Pharmaceutical Sciences. 4(4), 145-154.‏
24. Madrakian T., Afkhami A., Khalafi L., Mohammadnejad M., 2006. Spectrophotometric determination of catecholamines based on their oxidation reaction followed by coupling with 4-aminobenzoic acid. Journal of the Brazilian Chemical Society. 17, 1259-1265.‏
25. Majekodunmi S.O., Oyagbemi A.A., Umukoro S., Odeku O.A., 2011. Evaluation of the anti–diabetic properties of Mucuna pruriens seed extract. Asian Pacific Journal of Tropical Medicine. 4(8), 632-636.
26. Madrakian T., Afkhami A., Borazjani M., Bahram M., 2004. Simultaneous derivative spectrophotometric determination of levodopa and carbidopa in pharmaceutical preparations. Bulletin of the Korean Chemical Society. 25(12), 1764-1768.‏
27. 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.
28. Pan L., Guo Y., Li Z., Chen J., Jiang T., Yu Y., 2010. Simultaneous determination of Levodopa, Benserazide, and 3-O-Methyldopa in Human serum by LC–MS–MS. Chromatographia. 72, 627-633.‏
29. Zheng J.Q., Jin J.Z., Chen L.P., Li H.L., 2010. HPLC determination of the content of methyldopa and its related substances. Chinese Journal of Pharmaceutical Analysis. 30(8), 1440-1444.‏
30. Elbarbry F., Nguyen V., Mirka A., Zwickey H., Rosenbaum R., 2019. A new validated HPLC method for the determination of levodopa: Application to study the impact of ketogenic diet on the pharmacokinetics of levodopa in Parkinson's participants. Biomedical Chromatography. 33(1), e4382.‏
31. Baranowska I., Płonka J., 2008. Determination of levodopa and biogenic amines in urine samples using high-performance liquid chromatography. Journal of Chromatographic Science. 46(1), 30-34.‏
32. Jiang R., Yang J., Mei S., Zhao Z., 2022. Determination of levodopa by chromatography-based methods in biological samples: a review. Analytical Sciences. 38(8), 1009-1017.‏
33. Calam T.T., 2021. Selective and sensitive determination of paracetamol and levodopa using electropolymerized 3, 5‐diamino‐1, 2, 4‐triazole film on glassy carbon electrode. Electroanalysis. 33(4), 1049-1062.‏
34. Bergamini M.F., Santos A.L., Stradiotto N.R., Zanoni M.V.B., 2005. A disposable electrochemical sensor for the rapid determination of levodopa. Journal of Pharmaceutical and Biomedical Analysis. 39(1-2), 54-59.‏
35. Sanati A.L., Faridbod F., 2017. Electrochemical determination of methyldopa by graphene quantum dot/1-butyl-3-methylimidazolium hexafluoro phosphate nanocomposite electrode. International Journal of Electrochemical Science. 12(9), 7997-8005.‏
36. Shahrokhian S., Saberi R.S., Kamalzadeh Z., 2011. Sensitive electrochemical sensor for determination of methyldopa based on polypyrrole/carbon nanoparticle composite thin film made by in situ electropolymerization. Electroanalysis. 23(9), 2248-2254.‏
37. Potts K.T., Huseby R.M., 1966. 1, 2, 4-Triazoles. XVI. Derivatives of the s-Triazolo [3, 4-b][1, 3, 4] thiadiazole Ring System1. The Journal of Organic Chemistry. 31(11), 3528-3531.‏
38. Noolvi M.N., Patel H.M., Kamboj S., Cameotra S.S., 2016. Synthesis and antimicrobial evaluation of novel 1, 3, 4-thiadiazole derivatives of 2-(4-formyl-2-methoxyphenoxy) acetic acid. Arabian Journal of Chemistry. 9, S1283-S1289
39. Payton M., Bush T.L., Chung G., Ziegler B., Eden P., McElroy P., Ross S., Cee V.J., Deak H.L., Hodous B.L., Nguyen H.N., 2010. Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Research. 70(23), 9846-9854.
40. Cee V.J., Schenkel L.B., Hodous B.L., Deak H.L., Nguyen H.N., Olivieri P.R., Romero K., Bak A., Be X., Bellon S., Bus, T.L., 2010. Discovery of a potent, selective, and orally bioavailable pyridinyl-pyrimidine phthalazine Aurora kinase inhibitor. Journal of Medicinal Chemistry. 53(17), 6368-6377.
41. Loh Jr V.M., Cockcroft X.L., Dillon K.J., Dixon L., Drzewiecki J., Eversley P.J., Gomez S., Hoare J., Kerrigan F., Matthews I.T., Menear K.A., 2005. Phthalazinones. Part 1: The design and synthesis of a novel series of potent inhibitors of poly (ADP-ribose) polymerase. Bioorganic & Medicinal Chemistry Letters. 15(9), 2235-2238.
42. Menear K.A., Adcock C., Boulter R., Cockcroft X.L., Copsey L., Cranston A., Dillon K.J., Drzewiecki J., Garman S., Gomez S., Javaid H., 2008. 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2 H-phthalazin-1-one: a novel bioavailable inhibitor of poly (ADP-ribose) polymerase-1. Journal of Medicinal Chemistry. 51(20), 6581-6591.
43. Kumari A., Singh R. K., 2019. Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives. Bioorganic Chemistry. 89, 103021.‏
44. Martin T.A., Jiang W.G., 2010. Anti-cancer agents in medicinal chemistry (formerly current medicinal chemistry-anti-cancer agents). Anti-cancer Agents in Medicinal Chemistry. 10(1), 1.‏
45. Zhang M.Z., Chen Q., Yang G.F., 2015. A review of recent developments of indole-containing antiviral agents. European Journal of Medicinal Chemistry. 89, 421-441.‏
46. Sultan A.A., Saleh M.Y., Alkhalidi E.F.A., 2022. Nano-Hydroxyapatite Remineralization of In-Situ Induced Enamel Caries. Journal of Nanostructures. 12(4), 1067-1074.‏
47. Welsch M.E., Snyder S.A., Stockwell B.R., 2010. Privileged scaffolds for library design and drug discovery. Current Opinion in Chemical Biology. 14(3), 347-361.‏
48. de Sa Alves F.R., Barreiro E.J., Manssour Fraga C.A., 2009. From nature to drug discovery: the indole scaffold as a ‘privileged structure’. Mini Reviews in Medicinal Chemistry. 9(7), 782-793.‏
49. 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.
50. Evans B.E., Rittle K.E., Bock M.G., DiPardo R.M., Freidinger R.M., Whitter W.L., Lundell G.F., Veber D.F., Anderson P.S., Chang R.S.L., Lotti V.J., 1988. Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists. Journal of Medicinal Chemistry. 31(12), 2235-2246.
51. Verma S., S Prabhakar Y., 2015. Target-based drug design-a reality in virtual sphere. Current medicinal chemistry. 22(13), 1603-1630.‏
52. Saleh M. Y., Aldulaimi A. K. O., Saeed S. M., Adhab A. H. 2024. TiFe2O4@ SiO2–SO3H: A novel and effective catalyst for esterification reaction. Heliyon. 10, e26286.
53. Banoon S., Ali Z., Salih T., 2020. Antibiotic resistance profile of local thermophilic Bacillus licheniformis isolated from Maysan province soil. Comunicata Scientiae. 11, e3291-e3291.
54. Serban G., Stanasel O., Serban E., Bota S., 2018. 2-Amino-1, 3, 4-thiadiazole as a potential scaffold for promising antimicrobial agents. Drug Design, Development and Therapy. 1545-1566.