Synthesis, Characterization and Biological Evaluation of Novel Thiourea Derivatives

Yıl 2022, Cilt: 12 Sayı: 2, 533 - 540, 30.06.2022

Fatih Tok Cansel Çakır Dilaycan Çam Mustafa Murat Kırpat Yusuf Sıcak

https://doi.org/10.33808/clinexphealthsci.1062872

Cited By: 1

Öz

Objective: A new series of 4-[3-(substitutedphenyl)thioureido]-N-(6-chloropyrazin-2-yl)benzenesulfonamide were synthesized from sulfaclozine.
Methods: All compounds were characterized by IR, 1H-NMR spectroscopic methods and elemental analysis. In addition to the antioxidant activity of the synthesis series, enzyme inhibition activities such as anticholinesterase, tyrosinase, α-amylase and α-glycosidase were determined for the first time in this study.
Results: According to these biological activity test results, compound 2a in the DPPH, 2c in the ABTS˙+ assay exhibited more antioxidant activity than reference standard. All thiourea derivatives demonstrated good BChE inhibitory activity than galantamine. Among the compounds, 2e and 2f showed the best tyrosinase enzyme inhibition activity, while 2g had the best α-amylase and α-glucosidase enzyme inhibition activity. In addition, we evaluated the druglikeness properties of compounds and their oral bioavailability were also found to be high.
Conclusion: Thiourea derivatives exhibited remarkable antioxidant activity and enzyme inhibition activity against tyrosinase, cholinesterase, α-amylase and α-glucosidase.

Anahtar Kelimeler

Thiourea, antioxidant, anticholinesterase, tyrosinase, α-amylase.

Teşekkür

The starting compound, sulfaclozine sodium monohydrate, was obtained from Medicavet A.Ş.

Kaynakça

• [1] Akhter S, Ullah S, Yousuf S, Wahab A, Siddiqui H, Choudhary MI. Synthesis, crystal structure and Hirshfeld Surface analysis of benzamide derivatives of thiourea as potent inhibitors of α-glucosidase in-vitro. Bioorg Chem 2021;107:1-9.
• [2] Teke Tuncel S, Erol Gunal S, Ekizoglu M, Gokhan Kelekci N, Erdem SS, Bulak E, Frey W, Dogan I. Thioureas and their cyclized derivatives: Synthesis, conformational analysis and antimicrobial evaluation. J Mol Struct 2019;1179:40- 56.
• [3] Bai W, Ji J, Huang Q, Wei W. Synthesis and evaluation of new thiourea derivatives as antitumor and antiangiogenic agents. Tetrahedron Lett 2020;61:1-7.
• [4] Krzywik J, Maj E, Nasulewics Goldeman A, Mozga W, Wietrzyk J, Huczynski A. Synthesis and antiproliferative screening of novel doubly modified colchicines containing urea, thiourea and guanidine moieties. Bioorg Med Chem Lett 2021;47:1-6.
• [5] Maalik A, Rahim H, Saleem M, Fatima N, Rauf A, Wadood A, Malik MI, Ahmed A, Rafique H, Zafar MN, Riaz M, Rasheed L, Mumtaz A. Synthesis, antimicrobial, antioxidant, cytotoxic, antiurease and molecular docking studies of N-(3- trifluoromethyl)benzoyl-N′-aryl thiourea derivatives. Bioorg Chem 2019;88:1-9.
• [6] Davies TQ, Tilby MJ, Skolc D, Hall A, Willis MC. Primary sulfonamide synthesis using the sulfinylamine reagent N-Sulfinyl-O-(tert-butyl)hydroxylamine, t-BuONSO. Org Lett 2020;22:9495-9499.
• [7] Mondal S, Malakar S. Synthesis of sulfonamide and their synthetic and therapeutic applications: Recent advances. Tetrahedron 2020;76:1-28.
• [8] Elgemeie GH, Azzam RA, Elsayed RE. Sulfa drug analogs: new classes of N-sulfonyl aminated azines and their biological and preclinical importance in medicinal chemistry (2000–2018). Med Chem Res 2019;28:1099-1131.
• [9] Kollu U, Avula VKR, Vallela S, Pasupuleti VR, Zyryanov GV, Neelam YS, Chamarthi NR. Synthesis, antioxidant activity and bioinformatics studies of L-3-hydroxytyrosine templated N-alkyl/aryl substituted urea/thioureas. Bioorg Chem 2021;111:1-13.
• [10] Yiğit M, Barut Celepci D, Taslimi P, Yiğit B, Çetinkaya E, Özdemir İ, Aygün M, Gülçin İ. Selenourea and thiourea derivatives of chiral and achiral enetetramines: Synthesis, characterization and enzyme inhibitory properties. Bioorg Chem 2022;120:1- 10.
• [11] Dayma V, Chopra J, Sharma P, Dwivedi A, Tripathi IP, Bhargava A, Murugesan V, Goswami AK, Baroliya PK. Synthesis, antidiabetic, antioxidant and anti-inflammatory activities of novel hydroxytriazenes based on sulpha drugs. Helijon 2020;6:1-10.
• [12] Ovais S, Pushpalatha H, Reddy GB, Rathore P, Bashir R, Yaseen S, Dheyaa A, Yaseen R, Tanwar O, Akthar M, Samim M, Javed K. Synthesis and biological evaluation of some new pyrazoline substituted benzenesulfonylurea/thiourea derivatives as anti hyperglycaemic agents and aldose reductase inhibitors. Eur J Med Chem 2014;80:209-217.
• [13] Karakuş S, Tok F, Türk S, Salva E, Tatar G, Taşkın Tok T, Koçyiğit Kaymakçıoğlu B. Synthesis, anticancer activity and ADMET studies of N-(5-methyl-1,3,4-thiadiazol-2-yl)-4-[(3-substituted) ureido/thioureido]benzenesulfonamide derivatives. Phosphorus Sulfur 2018;193(8):528-534.
• [14] Türk S, Tok F, Erdoğan Ö, Çevik Ö, Taşkın Tok T, Koçyiğit Kaymakçıoğlu B, Karakuş S. Synthesis, anticancer evaluation and in silico ADMET studies on urea/thiourea derivatives from gabapentin. Phosphorus Sulfur 2021;196(4):382-388.
• [15] Marco GJ. A rapid method for evaluation of antioxidants. J Am Oil Chem Soc 1968;45:594-598.
• [16] Blois MS. Antioxidant determinations by the use of a stable free radical. Nature 1958;181:1199-1200.
• [17] Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 1999;26:1231-1237.
• [18] Sıcak Y, Şahin-Yağlıoğlu A, Öztürk M. Bioactivities and phenolic constituents relationship of Muğla thyme and pine honey of Turkey with the chemometric approach. J Food Meas Charact 2021;15:3694-3707.
• [19] Apak R, Güçlü K, Özyürek M, Karademir SE. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, Using their cupric ion reducing capability in the presence of neocuproine: CUPRAC Method. J Agr Food Chem 2004;52:7970-7981.
• [20] Ellman GL, Courtney KD, Andres V, Featherston RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88-95.
• [21] Hearing VJ. Methods in enzymology. 142nd ed. NewYork: Academic Press; 1987.p.154-165.
• [22] Quan NV, Xuan TD, Tran HD, Thuy NTD, Trang LT, Huong CT, Andriana Y, Tuyen PT. Antioxidant, α-amylase and α-glucosidase inhibitory activities and potential constituents of Canarium tramdenum bark. Molecules 2019;24(3):1-14.
• [23] Kim JS, Kwon CS, Son KH. Inhibition of alpha-glucosidase and amylase by luteolin, a flavonoid. Biosci Biotechnol Biochem 2000;64(11):2458-2461.
• [24] Gora M, Czopek A, Rapacz A, Dziubina A, Gluch Lutwin M, Mordyl B, Obniska J. Synthesis, anticonvulsant and antinociceptive activity of new hybrid compounds: Derivatives of 3-(3-Methylthiophen-2-yl)-pyrrolidine-2,5-dione. Int J Mol Sci 2020;21:1-21.
• [25] Arias F, Franco Montalban F, Romero M, Carrion MD, Camacho ME. Synthesis, bioevaluation and docking studies of new imidamide derivatives as nitric oxide synthase inhibitors. Bioorg Med Chem 2021;44:1-11.
• [26] Tok F, Koçyiğit Kaymakçıoğlu B. Design, synthesis and biological screening of novel 1,5-diphenyl-3-(4- (trifluoromethyl)phenyl)-2-pyrazoline derivatives. Acta Chim Slov 2020;67:1139-1147
• [27] Sıcak Y. Design and antiproliferative and antioxidant activities of furan-based thiosemicarbazides and 1,2,4-triazoles: their structure-activity relationship and SwissADME predictions. Med Chem Res 2021;30:1557-1568.
• [28] Sıcak Y. Synthesis, predictions of drug-kikeness and pharmacokinetic properties of some chiral thioureas as potent enzyme inhibition agents. Turk J Chem 2022; doi:10.3906/kim2107-27