Taner KARAOĞLU, Berrin ÖZÇELİK, Semra UTKU, Ningur NOYANALPAN, Mehtap GÖKÇE, Erdoğan BERÇİN

Synthesis and in vitro antimicrobial and cytotoxicity activities of 2-[(2-nitro-1-phenylalkyl) thio] benzoic acid derivaties

In this research 14 compounds were tested for their antimicrobial activity. The synthesis of 7 compounds corresponding to 2-[(2-nitro-1-phenyl-propyl)thio]benzoic acids 4 has not been reported before and 7 compounds corresponding to 2-[(2-nitro-1-phenyl-ethyl) thio]benzoic acid 3 were reported by our research group. The antibacterial activity of the title compounds was evaluated by 2 Gram (+) (Staphylococcus aureus, Bacillus subtilis) and 2 Gram (-)(Pseudomonas aeruginosa, Escherichia coli) microorganisms. The antifungal activity of the compounds was also determined against yeast-like fungi (Candida albicans, C. krusei). For antibacterial activity, ampicillin and for antifungal activity, fluconazole and ketoconazole have been used as reference compounds. All of the 2-[(2-nitro-1-phenyl-ethyl)thio]benzoic acid 3 derivatives were more active than the reference compound ketoconazole in the antifungal activity test. The title compounds were also screened by consecutive dilution to explore their toxicity to a Vero cell line. Except for 3d and 3e all of the compounds 3 exhibited lower toxicity than ketoconazole.

PDF

___

1.F. Schöfer and M. Schooh, Arzneimmittel-Forsch., 8, 374-376 (1948).
2.O. Schales and H.A. Grafee, J. Am. Chem. Soc. 74, 4486-4490 (1952).
3.A.D. Xorge and S.S. Jorge, J. Am. Chem. Soc. 75, 4581-4582 (1953).
4.L.F. Cason, US, 3,376,340(CL. 260-562)02 Apr. 1968, Appl. 23 Nov. 1965; 3pp. Ref. Chem Abst. 70, 3507b(1968).
5.P. Messinger, Arch. Pharm. (Weinheim, Ger) 30(6), 458-462 (1973).
6.T.A. Lies and J.W. Clapp., US 4, 038, 288 (Cl. 260-329S;C07D333/00), 26 Jul 1977, Appl 127, 825, 24 Mr1971; 16pp. Ref. Chem. Abst., 87 167565w (1977).
7.E. Berçin, M. Gökçe, U. Abbasoğlu and N. Noyanalpan, J. Fac. Pharm. Gazi, 12(2) 117-128 (1995).
8.E. Berçin, M. Gökçe, B. Özçelik, M. Yurtsever and N. Noyanalpan, J. Fac. Pharm. Gazi, 12(2) 173-187(1995).
9.E. Berçin and M. Gökçe, J. Fac. Pharm. Gazi, 13(1) 33-44 (1996).
10.E. Berçin and S. Özgüçlü, J. Fac. Pharm. Gazi, 13(2) 133-142 (1996).
11.S. Özgüçlü, M. Gökçe, E. Berçin, B. Özçelik, T. Karaoğlu and N. Noyanalpan, Archiv Der Pharmazie,submitted.
12.M. Gökçe, B. Özçelik, G. Bakır, T. Karaoğlu, E. Berçin, and N. Noyanalpan, Arzneim-Forsch., in press.
13.V. Climesova, J. Koci, M. Pour, J. Stachel, K. Waisser and J. Kaustova, Eur. J. Pharm. Chem,, 37, 409-418(2002).
14.J. Valdez, R. Cedillo, A. Hernandez-Campos, L.Yepez, F. Hernandez-Luis, G. Navarrete-Vazquez, A.Tapia, R.Cortes, M.Hernandez and R.Castillo, Bioorganic &; Medicinal Chem. Letters, 12, 2221-2224 (2002).
15.T.C. Kühler., M. Swanson, B. Christenson, C.A. Klintenberg, B. Lamm, J. Fagerhag, G. Roberto, M. Olwegard-Halvarsson, V. Shcherbuchin, T. Elebring and J.E. Sjöström, J. Med. Chem., 45, 4282-4299 (2002).
16.M. Andrzejewska, L. Yepez-Mulia, A. Tapia, R. Cedillo-Rivera, A.E. Laudy, B.J. Starosciak and Z. Kazimier-czuk, Eur. J. Pharm. Chem., 21, 323-329 (2004).
17.M. Gökçe, E. Berçin, J. Fac. Pharm. Gazi, 13(2) 153-160 (1996).
18.D.E. Worral, Organic Synthesis, Coll. Volume 1, 413-415 (1941).
19.M. Koremura, H. Oku, T. Shono, T. Nakanishi, Takamine Kenkyusho Nempo, 13, 198-204 (1961).
20.a) C. Thornsberry, J. Anhalt, A.L. Barry, L. Cotton, E.H. Gerlachö, R.N. Jones, R.A. Norton, NCCLS, 5,583-590 (1985). b) National Committee for Clinical Laboratory Standards: method for broth dilution antifungal susceptibility testing yeast; approved standard, M27-A, 15, NCCLS, 10, VA Medical Center, Tuscon (1996).
21.W.E. Walker, B.A. Waisbren, R.R. Martins, G.E. Bataiyas, Am. Clin. Path. 56, 687-692 (1971).
22.A. Hensten-Pettersen, Int. End. J., 21, 89-99 (1988).
23.J.M.T. Hamilton-Miller, International Journal of Antimicrobial Agents, 23, 209-212 (2004).
24.M.E. Jones, J.A. Karlowsky, D.C.Draghi, C. Thornsberry, D.F. Sahm and D. Nathwani, International Journal of Antimicrobial Agents, 23, 240-246 (2004).
25.G. Fadda, T. Spanu, F. Ardito , C. Taddei , R. Santangelo , A. Siddu, D. Ciccaglione, International Journal of Antimicrobial Agents, 23, 254-261 (2004).
26.Z. Wang, T. Jian , L.T. Phan and Y.S. Or, Bioorganic &: Medicinal Chemistry Letters, 14, 519-521 (2004)
27.J.A. Dromigny, B. Ndoye, E.A. Macondo, P. Nabeth, T. Siby and J. D.Perrier-Gros-Claude, Diagnostic Microbiology and Infectious Disease, 47, 595-600 (2003).
28.A.D. Russell, The Lancet Infectious Diseases, 3, 794-803 (2003).
29.H. Hanaki, Y. Yamaguchi, S. Nomura, I Haraga, A. Nagayama, K. Sunakawa, International Journal of Antimicrobial Agents, 23, 1-5 (2004).
30.H.V. Melckebeke, C. Vreuls, P. Gans, P. Filee, G. Liabres, B. Joris, and J.P. Simorre, Journal of Molecular Biology, 333, 711-720 (2003).
31.T. Korpimaki, J. Kurittu, M. Karp, Journal of Microbiological Methods, 53, 37-42 (2003).
32.L.E. Nunez, C. Mendez, A.F. Brana, G. Blanco and J.A. Salas, Chemistry &; Biology, 10, 301-311(2003).
33.S.K. Bouchillon, D.J. Hoban, J.L. Johnson, B.M. Johnson, D.L. Butler, K.A. Saunders, L.A. Miller, and J.A.Poupard, International Journal of Antimicrobial Agents, 23, 181-196 (2004).
34.P. Butaye, A. Cloeckaert and S. Schwarz, International Journal of Antimicrobial Agents, 22, 205-210(2003).
35.U. Odakowska-Jedynak, L. Paczek, M. Krawczyk, K. Zieniewicz, P. Nckowski, J. Pawlak, W. Patkowski, A.Skwarek and A. Paczkowska, Transplantation Proceedings, 35, 2304-2306 (2003).
36.Yee Y.C., Clinical Microbiology Newsletter, 25, 9-16 (2003).
37.M.A. Abraham, P.P. Thomas, G.T. John, V. Job, Shankar V., Jacob C. K., Transplantation Proceedings,35, 215-216 (2003).
38.E.M. Abdel-Moety, F.I. Khattab, K.M. Kelani and A.M. AbouAl-Alamein, II Farmaco, 57, 931-938 (2003).
39.Bonhomme-Faivre L., Forestier F., Auchere D., Soursac M., Orbach- Arbouys S., Farinotti R., International Journal of Pharmaceutics, 238, 133-137 (2002).
40.D. Cordoba-Diaz, M. Cordoba-Diaz, S. Awad,and M. Cordoba-Borrego, International Journal of Pharmaceutics, 226, 61-68 (2001).
41.J.R. Cupp-Vickery, C. Garcia, A. Hofacre, K. McGee-Estrada, Journal of Molecular Biology, 311, 101-110(2001).
42.M.E. Carroll, U. C. Campbell and P. Heideman, Experimental and Clinical Psychopharmacology, 9,307-316 (2001).