Novel Straight-chained Sulfanyl Members of Arylamino-1,4-naphthoquinones: Synthesis and Characterization

Abstract

The aim of this paper is to describe the synthesis and characterization of new members of straight-chained sulfanyl derivatives of arylamino-1,4-naphthoquinones. 2-(4-(trifluoromethyl)phenylamino)-3-chloronaphthalene-1,4-dione (3a) and 2-(3-(trifluoromethyl)phenylamino)-3-chloronaphthalene-1,4-dione (3b) compounds which prepared by means of nucleophilic substitution reactions between 2,3-dichloro-1,4-naphthoquinone (1) and arylamines containing trifluoro group at meta and para positions (2a, 2b) were used as building blocks for straight-chained sulfanyl arylamino-1,4-naphthoquinones. The structures of all the novel compounds (5a-f) were established by spectroscopic evidence including IR, ¹H NMR, ¹³C NMR, and MS data.

Keywords

• Sulfanyl 1,4-naphthoquinone,Arylamine,Trifluoromethyl group

References

1. 1. Cole ST. Who will develop new antibacterial agents? Philos T R Soc B. 2014;369(1645).
2. 2. Tandon VK, Maurya HK, Mishra NN, Shukia PK. Design, synthesis and biological evaluation of novel nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents. Eur J Med Chem. 2009;44(8):3130-7.
3. 3. Kumagai Y, Shinkai Y, Miura T, Cho AK. The Chemical Biology of Naphthoquinones and Its Environmental Implications. Annu Rev Pharmacol. 2012;52:221-47.
4. 4. Salas CO, Faundez M, Morello A, Maya JD, Tapia RA. Natural and Synthetic Naphthoquinones Active Against Trypanosoma Cruzi: An Initial Step Towards New Drugs for Chagas Disease. Curr Med Chem. 2011;18(1):144-61.
5. 5. Pinto AV, de Castro SL. The Trypanocidal Activity of Naphthoquinones: A Review. Molecules. 2009;14(11):4570-90.
6. 6. Klaus V, Hartmann T, Gambini J, Graf P, Stahl W, Hartwig A, et al. 1,4-Naphthoquinones as inducers of oxidative damage and stress signaling in HaCaT human keratinocytes. Arch Biochem Biophys. 2010;496(2):93-100.
7. 7. Kim TJ, Yun YP. Antiproliferative activity of NQ304, a synthetic 1,4-naphthoquinone, is mediated via the suppressions of the PI3K/Akt and ERK1/2 signaling pathways in PDGF-BB-stimulated vascular smooth muscle cells. Vasc Pharmacol. 2007;46(1):43-51.
8. 8. Ryu CK, Shim JY, Chae MJ, Choi IH, Han JY, Jung OJ, et al. Synthesis and antifungal activity of 2/3-arylthio- and 2,3-bis(arylthio)-5-hydroxy-/5-methoxy-1,4-naphthoquinones. Eur J Med Chem. 2005;40(5):438-44.

9. 9. Brimble MA, Duncalf LJ, Nairn MR. Pyranonaphthoquinone antibiotics - isolation, structure and biological activity. Nat Prod Rep. 1999;16(3):267-81.
10. 10. Qabaja G, Jones GB. Annulation strategies for benzo[b]fluorene synthesis: Efficient routes to the kinafluorenone and WS-5995 antibiotics. J Org Chem. 2000;65(21):7187-94.
11. 11. Uno H. Synthesis of Naturally-Occurring Quinones .17. Allylation of 2-Alkanoyl 1,4-Quinones with Allylsilanes and Allylstannanes - Efficient Synthesis of Pyranonaphthoquinone Antibiotics. J Org Chem. 1986;51(3):350-8.
12. 12. Benites J, Valderrama JA, Bettega K, Pedrosa RC, Calderon PB, Verrax J. Biological evaluation of donor-acceptor aminonaphthoquinones as antitumor agents. Eur J Med Chem. 2010;45(12):6052-7.
13. 13. Samant BS, Chakaingesu C. Novel naphthoquinone derivatives: Synthesis and activity against human African trypanosomiasis. Bioorg Med Chem Lett. 2013;23(5):1420-3.
14. 14. Druzhinin SV, Balenkova ES, Nenajdenko VG. Recent advances in the chemistry of alpha,beta-unsaturated trifluoromethylketones. Tetrahedron. 2007;63(33):7753-808.
15. 15. Tandon VK, Maurya HK, Yadav DB, Tripathi A, Kumar M, Shukla PK. Naphtho[2,3-b][1,4]-thiazine-5,10-diones and 3-substituted-1,4-dioxo-1,4-dihydronaphthalen-2-yl-thioalkanoate derivatives: Synthesis and biological evaluation as potential antibacterial and antifungal agents. Bioorg Med Chem Lett. 2006;16(22):5883-7.
16. 16. Tandon VK, Maurya HK, Tripathi A, ShivaKeshava GB, Shukla PK, Srivastava P, et al. 2,3-Disubstituted-1,4-naphthoquinones, 12H-benzo[b]phenothiazine-6, 11-diones and related compounds: Synthesis and Biological evaluation as potential antiproliferative and antifungal agents. Eur J Med Chem. 2009;44(3):1086-92.
17. 17. Bayrak N, Yildirim H, Tuyun AF, Kara EM, Celik BO, Gupta GK. Synthesis, Biological, and Computational Study of Naphthoquinone Derivatives Containing Heteroatoms. J Chem Soc Pakistan. 2016;38(6):1211-21.
18. 18. Bhasin D, Chettiar SN, Etter JP, Mok M, Li PK. Anticancer activity and SAR studies of substituted 1,4-naphthoquinones. Bioorg Med Chem. 2013;21(15):4662-9.
19. 19. Bayrak N, Yildirim H, Tuyun AF, Kara EM, Celik BO, Gupta G.K, Ciftci H, Fujita M, Otsuka M., Nasiri H.R. Synthesis, Computational Study, and Evaluation of in vitro Antimicrobial, Antibiofilm, and Anticancer Activities of New Sulfanyl Aminonaphthoquinone Derivatives. Lett Drug Des Discov. In press, DOI: 10.2174/1570180813666161020164931
20. 20. Tuyun AF, Bayrak N, Yildirim H, Onul N, Kara EM, Celik BO. Synthesis and In Vitro Biological Evaluation of Aminonaphthoquinones and Benzo[b]phenazine-6,11-dione Derivatives as Potential Antibacterial and Antifungal Compounds. J Chem. 2015.
21. 21. Buu-Hoi NPR, R.; Hubert-Habart, M., Empêchement stérique dans la réaction des amines sur les quinones halogénées. Recl Trav Chim Pay B. 1954;73:188-92.
22. 22. Mital AS, M.; Bindal, S.; Mahlavat, S.; Negi, V., Substituted 1,4-naphthoquinones as a new class of antimycobacterial agents Der Pharma Chem 2010;2:63-73.