Design, synthesis and biological evaluation of 1,3-diaryltriazenesubstituted sulfonamides as antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitors

Year 2019, Volume: 6 Issue: 1, 63 - 70, 15.05.2019

Süleyman Akocak Mehmet Boga Nabih Lolak Muhammed Tuneg Rajesh K K Sanku

https://doi.org/10.18596/jotcsa.516444

Cited By: 15

Abstract

1,3-diaryltriazenes are one of the most useful and
important linkers for many pharmaceutical applications. Therefore, in the
current work, a series of 1,3-diaryltriazene sulfonamides 4(a-k) were synthesized by reacting diazonium salt of sulfanilamide
and substituted aromatic amine derivatives 3(a-k).
The obtained compounds were investigated for antioxidant properties by using
different methods such as a DPPH radical scavenging assay, ABTS radical
decolarization, cupric reducing antioxidant capacity (CUPRAC) and metal
chelating methods. The cholinesterase inhibition activities
(acetylcholinesterase and butyrylcholinesterase) of synthesized compounds were
also tested. In general, compounds showed weak antioxidant activity, except
compounds 4d (IC₅₀
=114.89 for DPPH activity), 4i (IC₅₀
=25.31 for ABTS activity), 4a (IC₅₀
= 86.33 for metal chelating activity), and 4k
(absorbance value 1.229 µM for CUPRAC). Some of the compounds showed great %
inhibition against both acetylcholinesterase and butyrylcholinesterase with %
inhibition values ranging from 11.54 to 93.67 and 62.24 to 98.47, respectively. 

Keywords

antioxidant, 1;3-diaryltriazene, sulfanylamide

References

• 1. Konda S, Srujana R, Bhaskar K, Munaganti RK, Gugloth V, Nagarapu L, Akkewar DM. Synthesis and antimicrobial activity of novel benzoxazine sulfonamide derivatives. Bioorg Med Chem Lett. 2015;25(7):1643.1646.
• 2. Durgun M, Turkmen H, Zengin G, Zengin H, Koyunsever M, Koyuncu I. Synthesis, characterization, in vitro cytotoxicity and antimicrobial investigation and evaluation of physicochemical properties of novel 4-(2-methylacetamide)benzenesulfonamide derivatives. Bioorg Chem. 2017;70:163-172.
• 3. Genc Y, Ozkanca R, Bekdemir Y. Antimicrobial activity of some sulfonamide derivatives on clinical isolates of Staphylococus aureus. Ann Clin Microbiol Antimicrob. 2008 Aug;(7):17-23.
• 4. Chandna N, Kumar S, Kaushik P, Kaushik D, Roy SK, Gupta GK, Jachak SM, Kapoor JK, Sharma PK. Synthesis of novel celecoxib analogues by bioisosteric replacement of sulfonamide as potent anti-inflammatory agents and cyclooxygenase inhibitors. Bioorg Med Chem. 2013;21(15):4581-4590.
• 5. Bano S, Javed K, Ahmad S, Rathish IG, Singh S, Alam MS. Synthesis and biological evaluation of some new 2-pyrazolines bearing benzene sulfonamide moiety as potential anti-inflammatory and anti-cancer agents. Eur J Med Chem. 2011;46(12):5763-5768.
• 6. Gocer H, Akincioglu A, Oztaskin N, Goksu S, Gulcin I. Synthesis, antioxidant, and antiacetylcholinesterase activities of sulfonamide derivatives of dopamine-related compounds. Arch Pharm. 2013 Oct;346(11):783-792.
• 7. Ning X, Guo Y, Ma X, Zhu R, Tian C, Zhang Z, Wang X, Ma Z, Liu J. Design, synthesis and pharmacological evaluation of (E)-3,4-dihydroxy styryl sulfonamides derivatives as multifunctional neuroprotective agents against oxidative and inflammatory injury. Bioorg Med Chem. 2013;21(17):5589-5597.
• 8. Garibov E, Taslimi P, Sujayev A, Bingol Z, Cetinkaya S, Gulcin I, Beydemir S, Farzaliyev V, Alwasel SH, Supuran CT. Synthesis of 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines and investigation of their acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I/II inhibitory and antioxidant activities. J Enzyme Inhib Med Chem. 2016;31:1-9.
• 9. Lu XY, Wang ZC, Ren SZ, Shen FQ, Man RJ, Zhu HL. Coumarin sulfonamides derivatives as potent and selective COX-2 inhibitors with efficacy in suppressing cancer proliferation and metastasis. Bioorg Med Chem Lett. 2016;26(15):3491-3498.
• 10. Akocak S, Alam MR, Shabana AM, Sanku RKK, Vullo D, Thompson H, Swenson ER, Supuran CT, Ilies MA. PEGylated Bis-sulfonamide carbonic anhydrase inhibitors can efficiently control the growth of several carbonic anhydrase IX-expressing carcinomas. J Med Chem 2016;59(10):5077-5088.
• 11. Lolak N, Akocak S, Bua S, Supuran CT. Design, synthesis and biological evaluation of novel ureido benzenesulfonamides incorporating 1,3,5-triazine moieties as potent carbonic anhydrase IX inhibitors. Bioorg Chem. 2019;82:117-122.
• 12. Casini A, Scozzafava A, Mastrolorenzo A, Supuran CT. Sulfonamides and sulfonylated derivatives as anticancer agents. Curr Cancer Drug Targetd. 2002;2(1):55-75.
• 13. Canakci D, Koyuncu I, Lolak N, Durgun M, Akocak S, Supuran CT. Synthesis and cytotoxic activities of novel copper and silver complexes of 1,3-diaryltriazene-substituted sulfonamides. J Enzyme Inh Med Chem. 2019;34(1):110-116.
• 14. Zhao C, Rakesh KP, Ravidar L, Fang WY, Qin HL. Pharmaceutical and medicinal significance of sulfur (SVI)-containing motifs for drug discovery: A critical review. Eur J Med Chem. 2019;162:679-734.
• 15. Akocak S, Lolak N, Nocentini A, Karakoc G, Tufan A, Supuran CT. Synthesis and biological evaluation of novel aromatic and heterocyclic bis-sulfonamide Schiff bases as carbonic anhydrase I, II, VII and IX inhibitors. Bioorg Med Chem. 2017;25(12):3093-3097.
• 16. Akocak S, Lolak N, Bua S, Turel I, Supuran CT. Synthesis and biological evaluation of novel N,N`-diaryl cyanoguanidines acting as potent and selective carbonic anhydrase II inhibitors. Bioorg Chem. 2018;77:245-251.
• 17. El-Gazzar MG, Nafie NH, Nocentini A, Ghorab MM, Heiba HI, Supuran CT. Carbonic anhydrase inhibition with a series of novel benzenesulfonamide-triazole conjugates. J Enzyme Inhib Med Chem. 2018;33(1):1565-1574.
• 18. Bag S, Tulsan R, Sood A, Cho H, Redjeb H, Zhou W, LeVine H, Torok B, Torok M. Sulfonamides as multifunctional agents for Alzheimer’s disease. Bioorg Med Chem Lett. 2015;25(3):626-630.
• 19. Rishton GM, Retz DM, Tempest PA, Novontny J, Kahn S, Treanor JJ, Lile JD, Ciltron M. Fencyhylamine sulfonamide inhibitors of amyloid beta peptide production by the gamma-secretase proteolytic pathway: potential small-molecule therapeutic agents for the treatment of Alzheimer’s disease. J Med Chem. 2000;43(12):2297-2299.
• 20. Wang J, Gu BJ, Masters CL, Wang YJ. A systemic view of Alzheimer disease-insights from amyloid-β metabolism beyond the brain. Nat Rev Neurol. 2017;13(10):612-623.
• 21. Swerdlow RH. Pathogenesis of Alzheimer’s disease. Clin Interv Aging. 2007;2(3):347-359.
• 22. Dong S, Duan Y, Hu Y, Zhao Z. Advances in the pathogenesis of Alzheimer’s disease: a re-evaluation of amyloid cascade hypothesis. Transl Neurodegener. 2012;1(1):1-18.
• 23. Greig NH, Lahiri DK, Sambamurti K. Butyrylcholinesterase: an important new target in Alzheimer’s disease therapy. Int Psychogeriatr. 2002;14:77-91.
• 24. Gulcin I, Scozzafav A, Supuran CT, Akincioglu H, Koksal Z, Turkan F, Alwasel S. The effect of caffeic acid phenethyl ester (CAPE) on metabolic enzymes including acetylcholinesterase, butyrylcholinesterase, glutathione S-transferase, lactoperoxidase, and carbonic anhydrase isozymes I, II, IX, and XII. J Enzyme Inhib Med Chem. 2016;31(6):1095-1101.
• 25. Oztaskin N, Cetinkaya Y, Taslimi P. Goksu S, Gulcin I. Antioxidant and acetylcholinesterase inhibition properties of novel bromophenol derivatives. Bioorg Chem. 2015;60:49-57.
• 26. Casey DA, Antimisiaris D, O’Brien J. Drugs for Alzheimer’s disease: are they effective?. P T. 2010;35(4):208-211.
• 27. Klatte ET, Scharre DW, Nagaraja HN, Davis RA, Reversdorf DQ. Combination therapy of donepezil and vitamin E in Alzheimer disease. Alzheimer Dis Assoc Disord. 2003;17(2):113-116.
• 28. Cai P, Fang SQ, Yang HL, Yang XL, Liu QH, Kong LY, Wang XB. Donepezil-butylated hydroxytoluene (BHT) hybrids as Anti-Alzheimer’s disease agents with cholinergic, antioxidant, and neuroprotective properties. Eur J Med Chem. 2018;5(157):161-176.
• 29. Lolak N, Akocak S, Bua S, Koca M, Supuran CT. Design and synthesis of novel 1,3-diaryltriazene-substituted sulfonamides as potent and selective carbonic anhydrase II inhibitors. Bioorg Chem. 2018;77:542-547.
• 30. Akocak S, Lolak N, Bua S, Supuran CT. Discovery of novel 1,3-diaryltriazene sulfonamides as carbonic anhydrase I, II, VII, and IX inhibitors. J Enzyme Inhib Med Chem. 2018;33(1):1575-1580.
• 31. Blois MS. Antioxidant determinations by the use of a stable free radical. Nature. 1958;181:1199-1200.
• 32. Pellegrini RRN, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying and improved ABTS radical cation decolorization assay. Free Rad Bio Med. 1999;26:1231-1237.
• 33. Dinis TCP, Maderia VMC, Almedia LM. Action of phenolic derivatives (acetoaminophen, salycilate and 5-aminosalycilate) as inhibitors of membrane lipid preoxidation and as preoxyl radical scavengers. Arc Biochem Biophy. 1994;315:161-169.
• 34. Apak R, Guclu K, Ozyurek M, Karademir SE. Novel total antioxidant capacity index for dietary polyphenols and vitamine C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. J Agric Food Chem. 2004;52:7970-7981.
• 35. Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88-95.