Synthesis of novel acridine-sulfonamide hybrid compounds as acetylcholinesterase inhibitor for the treatment of alzheimer’s disease
- 80 Downloads
In this study we report that amino acridine intermediates 7 and 8 were obtained from the reduction of nitro acridine derivatives 5 and 6 that were synthesized via the condensation of dimedone, p-nitrobenzaldehyde with various amine derivatives, respectively. Then acridine sulfonamide hybrid compounds (9–18) were synthesized by the reaction of amino acridine 7, 8 with sulfonyl chlorides. The new hybrid compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, and HRMS analyzes. The evaluation of in vitro anticholinesterase action of the synthesized compounds against AChE showed that some of them are potent inhibitors. Among them, compound 17 showed the most potent activity against AChE with an IC50 of 0.14 µM.
KeywordsAnticholinesterase activity Tacrine Acridine Sulfonamide
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- Antonini I, Polucci P, Kelland RL, Menta E, Pescalli N, Martelli S (1999) 2,3-dihydro-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7-trione derivatives, a class of cytotoxic agents active on multidrug-resistant cell lines: synthesis, biological evaluation, and structure−activity relationships. J Med Chem 42:2535–2541CrossRefPubMedGoogle Scholar
- Marco-Contelles J, León R, Ríos CL, Samadi A, Bartolini M, Andrisano V, Huertas O, Barril X, Luque FJ, Rodríguez-Franco MI, López B, López MG, García AG, Carreiras MC, Villarroya M (2009) Tacripyrines, the first tacrine−dihydropyridine hybrids, as multitarget-directed ligands for the treatment of alzheimer’s disease. J Med Chem 52:2724–2732CrossRefPubMedGoogle Scholar
- Slawinski J, Brzozowski Z, Zolnowska B, Szafranski K, Pogorzelska A, Vullo D, Supuran CT (2014a) Synthesis of a new series of N 4-substituted 4-(2-aminoethyl)benzenesulfonamides and their inhibitory effect on human carbonic anhydrase cytosolic isozymes I and II and transmembrane tumor-associated isozymes IX and XII. Eur J Med Chem 84:59–67CrossRefPubMedGoogle Scholar
- Slawinski J, Pogorzelska A, Zolnowska B, Brozewicz K, Vullo D, Supuran CT (2014b) Carbonic anhydrase inhibitors. Synthesis of a novel series of 5-substituted 2,4-dichlorobenzenesulfonamides and their inhibition of human cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII. Eur J Med Chem 82:47–55CrossRefPubMedGoogle Scholar
- Srivastava A, Nizamuddin C (2004) Synthesis and fungicidal activity of some acridine derivatives. Indian J Heterocycl Chem 13:261–264Google Scholar
- Supuran CT, Scozzafava A (2001) Carbonic anhydrase inhibitors. Curr Med Chem 1:61–97Google Scholar
- Tang ZQ, Chen Y, Liu CN, Cai KY, Tuc SJ (2010) A green procedure for the synthesis of 1,8-dioxodecahydroacridine derivatives under microwave irradiation in aqueous media without catalyst. J Heterocyclic Chem 47:363–367Google Scholar
- Zolnowska B, Slawinski J, Pogorzelska A, Chojnacki J, Vullo D, Supuran CT (2014) Carbonic anhydrase inhibitors. Synthesis, and molecular structure of novel series N-substituted N′-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl) guanidines and their inhibition of human cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII. Eur J Med Chem 71:135–147CrossRefPubMedGoogle Scholar