Preparation, structure elucidation, and antioxidant activity of new bis(thiosemicarbazone) derivatives

Schiff-base–bearing new bis(thiosemicarbazone) derivatives were prepared from terephthalaldehyde and various thiosemicarbazides. FT–IR, 1 H NMR, 13 C NMR, and UV–Vis spectroscopic methods and elemental analysis were used to elucidate the identification of the synthesized molecules. The in vitro antioxidant activity of the synthesized compounds was analysed with the 1,1-diphenyl-2-picryl hydrazyl free-radical–trapping process. The synthesized compounds exhibited lower antioxidant activity than the standard ascorbic acid. IC50 values of the synthesized molecules measured from 3.81 ± 0.01 to 29.05 ± 0.11 µM. Among the synthesized compounds, compound 3 had the best antioxidant activity. Moreover, this study explained the structure–activity relationship of the synthesized molecules with different substituents in radical trapping reactions

PDF

___

1. Aly MM, Mohamed YA, El-Bayouki KA, Basyouni WM, Abbas SY. Synthesis of some new 4(3H)-quinazolinone2-carboxaldehyde thiosemicarbazones and their metal complexes and a study on their anticonvulsant, analgesic, cytotoxic and antimicrobial activities–Part-1. European Journal of Medicinal Chemistry 2010; 45: 3365-3373.
2. Sriram D, Yogeeswari P, Thirumurugan R, Pavana RK. Discovery of new antitubercular oxazolyl thiosemicarbazones. Journal of Medicinal Chemistry 2006; 49: 3448-3450.
3. Pervez H, Saira N, Iqbal MS, Yaqub M, Khan KM. Synthesis and biological evaluation of some $N^4$-aryl-substituted5-fluoroisatin-3-thiosemicarbazones. Medicinal Chemistry Research 2013; 22: 5878-5889.
4. Stanojkovic TP, Kovala-Demertzi D, Primikyri A, Garcia-Santos I, Castineiras A et al. Zinc (II) complexes of 2-acetyl pyridine 1-(4-fluorophenyl)-piperazinyl thiosemicarbazone: synthesis, spectroscopic study and crystal structures–potential anticancer drugs. Journal of Inorganic Biochemistry 2010; 104: 467-476.
5. Güveli Ş, Turan K, Ülküseven B. Nickel(II)-PPh 3 complexes with ONS and ONN chelating thiosemicarbazones: synthesis and inhibition potential on influenza A viruses. Turkish Journal of Chemistry 2018; 42: 371-384.
6. Khandani M, Sedaghat T, Erfani N, Haghshenas MR, Khavasi HR. Synthesis, spectroscopic characterization, structural studies and antibacterial and antitumor activities of diorganotin complexes with 3-methoxysalicylaldehyde thiosemicarbazone. Journal of Molecular Structure 2013: 1037; 136-143.
7. Eğlence-Bakır S, Sacan O, Şahin M, Yanardag R, Ülküseven B. Dioxomolybdenum (VI) complexes with 3- methoxy salicylidene-N -alkyl substituted thiosemicarbazones. Synthesis, characterization, enzyme inhibition and antioxidant activity. Journal of Molecular Structure 2019; 1194: 35-41.
8. Muğlu H, Yakan H, Bakır T. Synthesis, spectroscopic studies, and antioxidant activities of novel thio/carbohydrazones and bis-isatin derivatives from terephthalaldehyde. Turkish Journal of Chemistry 2020; 44: 237-248.
9. Ateş D, Gulcan M, Gümüş S, Şekerci M, Özdemir S et al. Synthesis of bis(thiosemicarbazone) derivatives: definition, crystal structure, biological potential and computational analysis. Phosphorus, Sulfur, and Silicon and the Related Elements, 2018; 193: 14-22.
10. Muğlu H. Synthesis, characterization, and antioxidant activity of some new $N^4$-arylsubstituted-5-methoxyisatinβ -thiosemicarbazone derivatives. Research on Chemical Intermediates 2020; 46: 2083-2098.
11. Bingul M, Şenkuytu E, Saglam MF, Boga M, Kandemir H et al. Synthesis, photophysical and antioxidant properties of carbazole-based bis-thiosemicarbazones. Research on Chemical Intermediates 2019; 45: 4487-4499.
12. El Salam HAA, Yakout ESM, Nawwar GA, El-Hashash M, Mossa A-TH. Synthesis of some new 1,2,-triazoles containing olyl moiety and evaluation of their antimicrobial and antioxidant activities. Monatshefte für ChemieChemical Monthly 2017; 148: 291-304.
13. Mohan Sahoo B, Chandra Dinda S, Ravi Kumar B, Panda J, S Brahmkshatriya P. Design, green synthesis, and anti-inflammatory activity of Schiff base of 1,3,4-oxadiazole analogues. Letters in Drug Design & Discovery 2014; 11: 82-89.
14. Karekal MR, Mathada MBH. Synthesis, spectroscopic characterization, and biological screening of binuclear transition metal complexes of bicompartmental Schiff bases containing indole and resorcinol moieties. Turkish Journal of Chemistry 2013; 37: 775-795.
15. Aanandhi V, George S, Vaidhyalingam V. Synthesis and antimicrobial activities of 1-(5-substituted-2-oxo indolin3-ylidene)-4-(substituted pyridin-2-yl) thiosemicarbazide. Arkivoc 2008; 11: 187-194.
16. Zhu X, Wang C, Dang Y, Zhou H, Wu Z et al. The Schiff base N -salicylidene-O, S−dimethylthiophosphorylimine and its metal complexes: synthesis, characterization and insecticidal activity studies. Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry 2000; 30: 625-636.
17. Popp FD. Synthesis of potential anticancer agents. II. Some Schiff bases. Journal of Organic Chemistry 1961; 26: 1566-1568.
18. Solak N, Rollas S. Synthesis and antituberculosis activity of 2-(aryl/alkylamino)-5-(4-aminophenyl)-1,3,4-thiadiazoles and their Schiff bases. Arkivoc 2006; 12: 173-181.
19. Prakash CR, Raja S, Saravanan G. Synthesis, characterization and anticonvulsant activity of novel Schiff base of isatin derivatives. International Journal of Pharmacy and Pharmaceutical Sciences 2010; 2: 177-181.
20. Kıvrak A, Yılmaz C, Konuş M, Koca H, Aydemir S, Oagaz JA. Synthesis and biological properties of novel 1-methyl2-(2-(prop-2-yn-1-yloxy)benzylidene) hydrazine analogues. Turkish Journal of Chemistry 2018; 42: 306-316.
21. Dhar DN, Taploo C. Schiff-bases and their applications. Journal of Scientific & Industrial Research 1982; 41: 501-506.
22. Halliwell B, Gutteridge JM. Free radicals in biology and medicine. Oxford, UK: Oxford University Press, 2015.
23. Özyürek M, Bektaşoğlu B, Güçlü K, Apak R. Measurement of xanthine oxidase inhibition activity of phenolics and flavonoids with a modified cupric reducing antioxidant capacity (Cuprac) method. Analytica Chimica Acta 2009; 636: 42-50.
24. Tyagi YK, Kumar A, Raj HG, Vohra P, Gupta G et al. Synthesis of novel amino and acetyl amino-4-methylcoumarins and evaluation of their antioxidant activity. European Journal of Medicinal Chemistry 2005; 40: 413-420.
25. Zhang YM, Wang DD, Lin Q, Wei TB. Synthesis and anion recognition properties of thiosemicarbazone based molecular tweezers. Phosphorus, Sulfur, and Silicon and the Related Elements 2007; 183: 44-55.
26. Brand-Williams W, Cuvelier M-E, Berset C. Use of a free radical method to evaluate antioxidant activity. LWTFood Science and Technology 1995; 28: 25-30.
27. Naik N, Kumar HV, Vidyashree PB. Synthesis and evaluation of antioxidant potential of novel isatin analogues. Journal of Pharmacy Research 2011; 4: 2686-2689.
28. Çavuş MS, Yakan H, Muğlu H, Bakır T. Novel carbohydrazones including 5-substituted isatin: synthesis, characterization, and quantum-chemical studies on the relationship between electronic and antioxidant properties. Journal of Physics and Chemistry of Solids 2020; 140: 109362.
29. Er M, Ünver Y, Sancak K, Değirmencioğlu I, Karaoglu SA. Synthesis, characterization and cyclization reactions of some new bisthiosemicarbazones. Arkivoc 2009 ii: 149-167.
30. Kemp W. Organic spectroscopy. New York, NY, USA: Macmillan International Higher Education, 2017.
31. Williams D, Fleming I. RNA structure and NMR spectroscopy. Spectroscopic Methods in Organic Chemistry. New York, NY, USA: McGraw-Hill, 1996.
32. Sharma BK. Instrumental methods of chemical analysis. Meerut, India: Goel Publishing House Krishna Prakashan Media Ltd., 2005, pp. 124-130.
33. Reddy KHD, Lee S-M, Seshaiah K, Babu RK. Synthesis, characterization of thiosemicarabzone metal complexes and antioxidant activity in different in vitro model systems. Journal of the Serbian Chemical Society 2013; 78: 229-240.
34. Lu YH, Lu YW, Wu CL, Shao Q, Chen XL et al. UV–visible spectroscopic study of the salicyladehyde benzoylhydrazone and its cobalt complexes. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2006; 65(3-4): 695-701.
35. Subhashree GR, Haribabu J, Saranya S, Yuvaraj P, Krishnan DA et al. In vitro antioxidant, antiinflammatory and in silico molecular docking studies of thiosemicarbazones. Journal of Molecular Structure 2017; 1145: 160-169.
36. Božić A, Filipović N, Novakovic I, Bjelogrlić S, Nikolić J et al. Synthesis, antioxidant and antimicrobial activity of carbohydrazones. Journal of the Serbian Chemical Society 2017; 82: 495-508.
37. Bendary E, Francis RR, Ali HMG, Sarwat MI, El Hady S. Antioxidant and structure–activity relationships (SARs) of some phenolic and anilines compounds. Annals of Agricultural Sciences 2013; 58: 173-181.
38. Santos-Sánchez NF, Salas-Coronado R, Villanueva-Cañongo C, Hernández-Carlos B. Antioxidants. In: Emad Shalaby (editor). Antioxidant compounds and their antioxidant mechanism. IntechOpen 2019. doi: 10.5772/intechopen.85270
39. Mohammadpour M, Sadeghi A, Fassihi A, Saghaei L, Movahedian A et al. Synthesis and antioxidant evaluation of some novel ortho-hydroxypyridine-4-one iron chelators. Research in Pharmaceutical Sciences 2012; 7: 171-179.
40. Queiroz, MJR, Ferreira IC, Calhelha RC, Estevinho LM. Synthesis and antioxidant activity evaluation of new 7-aryl or 7-heteroarylamino-2,3-dimethylbenzo [ b ] thiophenes obtained by Buchwald–Hartwig C–N cross-coupling. Bioorganic Medicinal Chemistry 2007: 15; 1788-1794.
41. Zheng YZ, Deng G, Guo R, Chen DF, Fu ZM. Substituent effects on the radical scavenging activity of isoflavonoid. International Journal of Molecular Sciences 2019: 20; 397-407.
42. Lee CY, Sharma A, Semenya J, Anamoah C, Chapman KN, Barone V. Computational study of ortho-substituent effects on antioxidant activities of phenolic dendritic antioxidants. Antioxidants 2020: 9: 189-202.
43. Kiran G, Sarangapani M, Gouthami T, Narsimha Reddy AR. Synthesis, characterization, and antimicrobial and antioxidant activities of novel bis-isatin carbohydrazone derivatives. Toxicological Environmental Chemistry 2013; 95: 367-378.
44. Gudipati R, Reddy Anreddy, RN, Manda S. Synthesis, anticancer and antioxidant activities of some novel N - (benzo [d] oxazol-2-yl)-2-(7-or 5-substituted-2-oxoindolin-3-ylidene) hydrazinecarboxamide derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry 2011: 26; 813-818.
45. Sens L, Oliveira ASD, Mascarello A, Brighente I, Yunes RA et al. Synthesis, Antioxidant activity, acetylcholinesterase inhibition and quantum studies of thiosemicarbazones. Journal of the Brazilian Chemical Society 2018: 29; 343-352.