Nurten ALTANLAR, Ayhan Gülgün KILCIGİL, Canan KUŞ

Antimicrobial activity of some thiadiazolyl-and triazolylbenzimidazoles

Bu çalışmada,1-[(substitue tiyokarbamoilhidrazinkarbonil)metil]-2-fenil-lH-benzimidazoles, Ia- 13a, N-l(2-fenilbenz.imidazol-I-il metil)-[1,3,4]-tiyadiazol-2-il]-sübstitüe fenil amin, lb-13b, ve 5-(2-fenil benzimidazol-1-il- metil)-4-sübstitüe fenil-4H-l,2,4-triazoI-3-tiyon, lc-13c, türevi 39 adet bileşiğin antimikrobiyal aktiviteleri incelenmiştir. Bileşiklerin Minimum Inhibitor Konsantrasyon (MIK) değerleri Gram pozitif bakteriler olarak Staphylococcus aureus ve Bacillus subtilis, Gram negatif bakteri olarak Escherichia coli ve maya-benzeri funguslar olarak da Candida albicans, Candida krusei ve Candida parapsilosis'e karşı tüp diliisyoıı metodu kullanılarak saptanmıştır. Bileşiklerin hepsi S. aııreus, C. krusei ve C. parapsilosis'e karşı etkisiz bulunmuşlardır. 5b, 9a ve 13a bileşikleri C. albicans'a karşı 12.5 $mu$g/ml MIC değeriyle iyi antifungal aktivite göstermişlerdir.

Bazı tiyadiazolil- ve triazolilbenzimidazol türevlerinin antimikrobiyal aktiviteleri

In this study, thirty nine benzimidazole derivatives namely 1-[(substituted thiocarbamoylhydrazine carbonyl)methylI-2-phenyl- 1H-benzimidazoles la-13a, N-[(2-phenylhenzimidazol-1-yl methyl)-[1,3,4]-thiadiazole-2-yl]-substituted phenyl amines 1b-13b, and 5-(2-phenyl benzimidazol-1-yl-methyl)-4-substituted phenyl-4H-1,2,4-triazole-3-thiones lc-13c were screened for their antimicrobial activities. Minimum Inhibitory Concentration (MlC) values of the compounds were determined by the tube dilution method using Staphylococcus aureus and Bacillus subtilis as Gram positive, Escherichia coli as Gram negative bacteria and Candida albicans, Candida krusei and Candida parapsilosis as yeast-like fungi. All of the compounds were inactive against S. aureits, C. krusei and C. parapsilosis Compounds 5b, 9a and 13a (12.5 $mu$g/ml) showed good inhibitors activity against C. albicans.

PDF

___

1. Abdel-Rahman, A. E., Mahmoud, A. M., El-Naggar, G. M. and El-Sherief, H. A., “Synthesis and Biological Activity of Some New Benzimidazolyl-azetidin-2-ones and Thiazolidin-4-ones” Pharmazie, 38, 589-590 (1983).
2. Coburn, R. A., Clark, M. T., Evans, R. T. and Genco, R. J. “Substituted 2-(2-hydroxy- phenyl)benzimidazoles as Potential Agents for the Control of Periodontal Diseases” J. Med. Chem., 30, 205-208 (1987).
3. Göker, H., Tunçbilek, M., Ayhan, G. and Altanlar, N. “Synthesis and antimicrobial activity of some new benzimidazole carboxylates and carboxamides” Farmaco, 53, 415-420 (1998).
4. Kılcıgil, G. A., Tunçbilek, M., Altanlar, N. and Göker, H. “Synthesis of some new benzimidazole-carboxamides and evaluation of their antimicrobial activity”, Farmaco, 54, 562-565 (1999).
5. Soliman, F. S. G., Rida, S. M., Badawey, E. A. M and Kappe, T. “Synthesis of Substituted 3-Hydroxy-1H,5H-pyrido[1,2-a]benzimidazol-1-ones as Possible Antimicrobial and Antineoplastic Agents” Arch. Pharm., 317, 951-958 (1984).
6. Habib, N. S., Abdel-Hamid, S. and El-Hawash, M. “Synthesis of Benzimidazole Derivatives as Potential Antimicrobial Agents” Farmaco, 44, 1225-1232 (1989).
7. Khairnar, V. L., Lockhande, S. R., Patel, M. R. and Khadse, B. G. “Synthesis and Screening for Antitubercular Activity of Substituted-S-(pyrimidyl or quinolyl)-2-(thio or sulfonyl)- benzimidazoles” Bull. Haffkine Inst. 8 (1980) 67-70: Chemical Abstract, 95, 203833h (1981).
8. Islam, I., Skibo, E. B., Dorr, R. T. and Alberts, D. S. “Structure-Activity Studies of Antitumor Agents Based on Pyrrolo[1,2-a]benzimidazoles: New Reductive Alkylating DNA Cleaving Agents” J. Med. Chem., 34, 2954-2961 (1991).
9. Kruse, L. I., Ladd, D. L., Harrsch, P. B., McCabe, F. L., Mong, S. M., Faucette, L. and Johnson, R. “Synthesis, Tubulin Binding, Antineoplastic Evaluation, and Structure-Activity Relationships of Oncodazole Analogues” J. Med. Chem., 32, 409-417 (1989).
10. Habernickel, V. J. “Alkyl-5-heterocyclic-benzimidazolyl-carbamate Derivatives” Drugs made in Germany, 35, 97 (1992).
11. Fukuda, T., Morimoto, Y., Iemura, R., Kawashima, T., Tsukamoto, G. and Ito, K. “Efffects of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)-benzimidazole difumarate (KB-2413), a new antiallergic, on chemical mediators” Arzneim.-Forsch./Drug Res., 34, 801-805 (1984).
12. Fukuda, T., Saito, T., Tajima, S., Shimohara, K. and Ito, K. “Antiallergic effect of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)-benzimidazole difumarate (KB-2413)” Arzneim.-Forsch./Drug Res., 34, 805-810 (1984). Ankara Ecz. Fak. Derg., 33 (1) 1-6, 2004 9
13. Nakano, H., Inoue, T., Kawasaki, N., Miyataka, H., Matsumoto, H., Taguchi, T., Inagaki, N., Nagai, H. and Satoh, T. “Synthesis of benzimidazole derivatives as antiallergic agents 5-lipoxygenase inhibiting action” Chem. Pharm. Bull., 47, 1573-1578 (1999).
14. Nakano, H., Inoue, T., Kawasaki, N., Miyataka, H., Matsumoto, H., Taguchi, T., Inagaki, N., Nagai, H. and Satoh, T. “Synthesis and biological activities of novel antiallergic agents with 5-lipoxygenase inhibiting action” Bioorg. Med. Chem., 8, 373-380 (2000).
15. Can-Eke, B., Puskullu, M. O., Buyukbingol, E. and Iscan, M. “A study on the antioxidant capacities of some benzimidazoles in rat issues” Chemico-Biological Interactions, 113, 65-77 (1998).
16. Boschelli, D. H., Connor, D. T., Bornemeier, D. A., Dyer, R. D., Kennedy, J. A., Kuipers, P. J., Okonkwo, G. C., Schrier, D. J. and Wright, C.D. “1,3,4-Oxadiazole, 1,3,4-thiadiazole, and 1,2,4-triazole analogs of the fenamates: In vitro inhibition of cyclooxygenase and 5-lipoxygenase activities” J. Med. Chem., 36, 1802-1810 (1993).
17. Shams El-Dine, S. A. and Hazzaa, A. A. B. “Synthesis of compounds with potential fungicidal activity” Pharmazie, 29, 761-763 (1974).
18. Tsotinis, A., Varvaresou, A., Calogeropoulou, T., Siatra-Papastaikoudi, T. and Tiligada, A. “Synthesis and antimicrobial evaluation of indole containing derivatives of 1,3,4-thiadiazole, 1,2,4-triazole and their open-chair counterparts” Arzneim.-Forsch./Drug Res., 47, 307-310 (1997).
19. Witkowski, J. T., Robins, R. K., Khare, G. P. and Sidwell, R. W. “Synthesis and Antiviral Activity of 1,2,4-Triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides” J. Med. Chem., 16, 935-937 (1973).
20. Andreadou, I., Tasouli, A., Bofilis, E., Chrysselis, M., Rekka, E., Tsantili-Kakoulidou, A., Iliodromitis, E., Siatra, T. and Kremastinos, D. T. “Antioxidant activity of novel indole derivatives and protection of the myocardial damage in rabbits” Chem. Pharm. Bull., 50, 165-168 (2002).
21. Sahm, D. F., Washington, J. A., “Antibacterial Suspectibility Tests, Dilution Methods” in Am.Soc.Microbiol., Balowes, A. W. J., Hausler, K., Hermann, L., Shadomy, H. D. (Eds), Washington 5.Ed. 1105 (1991).
22. Kuş C, Ayhan-Kılcıgil G, Can-Eke B, and İşcan M, Synthesis and antioxidant properties of some novel benzimidazole derivatives on lipid peroxidation in the rat liver, Archives of Pharmacal Research (yayına kabul edildi).