İlker AVAN, Alaattin GÜVEN, Kıymet GÜVEN

Synthesis and antimicrobial investigation of some 5H-pyridazino[4,5-b]indoles

Synthesis and in vitro antimicrobial activities are reported for a series of 1,3,5-substituted 4-oxo-3,4-dihydro-5H-pyridazino[4,5-b]indole derivatives. Corresponding pyridazino[4,5-b]indoles were prepared from ethyl 3-formyl-1H-indole-2-carboxylate precursors and the functional group in question was installed with hydrazine and its derivatives. The purity and primary structures of pyridazino[4,5-b]indole were confirmed by IR, 1 H NMR, and 13C NMR spectroscopy and elemental analyses. All of the indoles were tested for in vitro antimicrobial activity against 8 isolates of bacteria and a fungus including Staphylococcus aureus NRRL B-767, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Proteus vulgaris NRRL-B123, Salmonella typhimurium NRRL B-4420, Bacillus subtilis NRRL 744, Listeria monocytogenes ATCC 7644, and Candida albicans by using broth microdilution test. All of the isolates showed moderate sensitivity against tested indoles and B. subtilis NRRL 744 was the most sensitive.

Anahtar Kelimeler:

Pyridazino[4, 5-b]indole, antimicrobial activity, b -carboline, indole

Synthesis and antimicrobial investigation of some 5H-pyridazino[4,5-b]indoles

Keywords:

Pyridazino[4, 5-b]indole, antimicrobial activity, b -carboline, indole,

PDF

___

(a) Sundberg, R. J. Indoles, Academic Press, San Diego, 1996; (b) Kochanowska-Karamyan, A. J.; Hamann, M. T. Chem. Rev. 2010, 110, 4489–4497; (c) Shiri, M. Chem. Rev. 2012, 112, 3508–3549.
(a) Monge, A.; Parrado, P.; Font, M.; Fernandez-Alvarez, E. J. Med. Chem. 1987, 30, 1029–1035; (b) Monge, A.; Aldana, I.; Alvarez, T.; Font, M.; Santiago, E.; Latre, J. A.; Bermejillo, M. J.; Lopez-Unzu, M. J.; FernandezAlvarez, E. J. Med. Chem. 1991, 34, 3023–3029; (c) El-Gendy, A.; El-Banna, H. Arch. Pharm. Res. 2001, 24, 21–
Monge, A.; Font, M.; Parrado, P.; Fernandez-Alvarez, E. Eur. J. Med. Chem. 1988, 23, 547–552.
Monge, A.; Aldana, I.; Losa, M. J.; Font, M.; Cenarruzabeitia, E.; Castiella, E.; Frechilla, D.; Santiago, E.; Deirujo, J. J. M.; Alberdi, E.; Lopez-Unzu, M. J. Arzneimittel-Forsch. 1993, 43-2, 1175–1180.
Font, M.; Monge, A.; Cuartero, A.; Elorriaga, A.; Martinez-Irujo, J. J.; Alberdi, E.; Santiago, E.; Prieto, I.; Lasarte, J. J.; Sarobe, P.; Borras, F. Eur. J. Med. Chem. 1995, 30, 963–971.
Li, R. D.; Zhai, X.; Zhao, Y. F.; Gong, P. Chinese Chem. Lett. 2007, 18, 1191–1194.
(a) Krajsovszky, G.; Matyus, P.; Riedl, Z.; Csanyi, D.; Hajos, G. Heterocycles 2001, 55, 1105–1111; (b) El-Kashef, H.; Farghaly, A. A. H.; Floriani, S.; Haider, N. Arkivoc 2003, 198–209.
(a) Lopez-de Cerain, A.; Garcia, E.; Gullon, A.; Alvarez, T.; Losa, M. J.; Monge, A. Arzneimittel-Forsch. 1994, 44-1, 310–312; (b) Picada, J. N.; daSilva, K. V. C. L.; Erdtmann, B.; Henriques, A. T.; Henriques, J. A. P. Mutat. Res.-Fund. Mol. M. 1997, 379, 135–149; (c) Cao, R. H.; Peng, W. L.; Wang, Z. H.; Xu, A. L. Curr. Med. Chem. 2007, 14, 479–500; (d) Chen, J.; Dong, X.; Liu, T.; Lou, J.; Jiang, C.; Huang, W.; He, Q.; Yang, B.; Hu, Y. Bioorg. Med. Chem. 2009, 17, 3324–3331.
Li, R. D.; Zhai, X.; Zhao, Y. F.; Yu, S.; Gong, P. Arch. Pharm. 2007, 340, 424–428.
Vin, V.; Leducq, N.; Bono, F.; Herbert, J. M. Biochem. Bioph. Res. Co. 2003, 310, 785–790.
Papadopoulos, V.; Baraldi, M.; Guilarte, T. R.; Knudsen, T. B.; Lacap`ere, J. J.; Lindemann, P.; Norenberg, M. D.; Nutt, D.; Weizman, A.; Zhang, M. R.; Gavish, M. Trends Pharmacol. Sci. 2006, 27, 402–409.
Hiremath, S. P.; Ullagaddi, A.; Shivaramayya, K.; Purohit, M. G. Indian J. Heterocycl. Chem. 1994, 3, 145–8.
(a) Kurumi, M.; Sasaki, K.; Takata, H.; Nakayama, T. Heterocycles 2000, 53, 2809–2819; (b) Nogrady, T.; Morris, L. Can. J. Chem. 1969, 47, 1999–2002; (c) Huntress, E. H.; Hearon, W. M. J. Am. Chem. Soc. 1941, 63, 2762– 2766; (d) Monge, A.; Aldana, I.; Lezamiz, I.; Fern´ andez-Alvarez, E. Synthesis 1984, 160–161.
(a) Dajka-Halasz, B.; Monsieurs, K.; Elias, O.; Karolyhazy, L.; Tapolcsanyi, P.; Maes, B. U. W.; Riedl, Z.; Hajos, G.; Dommisse, R. A.; Lemiere, G. L. F.; Kosmrlj, J.; Matyus, P. Tetrahedron 2004, 60, 2283–2291; (b) Franck, P.; Hostyn, S.; Dajka-Halasz, B.; Polonka-Balint, A.; Monsieurs, K.; Matyus, P.; Maes, B. U. W. Tetrahedron 2008, 64, 6030–6037.
(a) Tapolcsanyi, P.; Krajsovszky, G.; Ando, R.; Lipcsey, P.; Horvath, G.; Matyus, P.; Riedl, Z.; Hajos, G.; Maes, B. U. W.; Lemiere, G. L. F. Tetrahedron 2002, 58, 10137–10143; (b) Krajsovszky, G.; Karolyhazy, L.; Dunkel, P.; Boros, S.; Grillo, A.; Matyus, P. Arkivoc 2011, 229–253; (c) Matyus, P.; Maes, B. U. W.; Riedl, Z.; Hajos, G.; Lemiere, G. L. F.; Tapolcsanyi, P.; Monsieurs, K.; Elias, O.; Dommisse, R. A.; Krajsovszky, G. Synlett 2004, 1123–1139.
(a) Seitz, G.; Mohr, R. Chem. Ztg. 1987, 111, 81–82; (b) Haider, N.; Wanko, R. Heterocycles 1994, 38, 1805–1811; (c) Daly, K.; Nomak, R.; Snyder, J. K. Tetrahedron Letters 1997, 38, 8611–8614; (d) Nomak, R.; Snyder, J. K. Tetrahedron Letters 2001, 42, 7929–7933.
(a) Monge, A.; Palop, J. A.; Goni, T.; Fernandez-Alvarez, E. J. Heterocyclic Chem. 1986, 23, 141–144; (b) Ali, M. I. E. S. A. A.; Abdel-Fattah, A. M.; El-Reedy, A. M. Indian J. Chem. 1977, 15B, 64–66; (c) Monge Vega, A.; Palop, J. A.; Martinez, M. T.; Fernandez-Alvarez, E. J. Heterocyclic Chem. 1980, 17, 249–256; (d) Monge, A.; Palop, J. A.; Tabar, P.; Alvarez, E. F. J. Heterocyclic Chem. 1984, 21, 397–400.
Wolfe, J. P.; Li, J. J. In Tetrahedron Org. Chem. Series; Li, J. J.; Gordon, G., Eds.; Elsevier, Amsterdam, 2007. Monge Vega, A.; Palop, J. A.; Martinez, M. T.; Fernandez Alvarez, E. J. Heterocyclic Chem. 1980, 17, 249–256. Murakami, Y.; Yokoyama, Y.; Miura, T.; Hirasawa, H.; Kamimura, Y.; Izaki, M. Heterocycles 1984, 22, 1211–1216. Kabalka, G. W.; Varma, R. S. Org. Prep. Proced. Int. 1987, 19, 283–328.
Blatter, H. M.; Lukaszewski, H.; De Stevens, G. Org. Synth. 1963, 43, 58–59.
Guven, A.; Jones, R. A. J. Chem. Res.-S 1993, (9), 362–363.
Johnson, J. R.; Hasbrouck, R. B.; Dutcher, J. D.; Bruce, W. F. J. Am. Chem. Soc. 1945, 67, 423–430.
Kuuloja, N.; Tois, J.; Franz´en, R. Tetrahedron: Asymmetry 2011, 22, 468–475.
Samsoniya, S. A.; Kalatozishvili, A. Z.; Chikvaidze, I. S.; Stolz, D.; Kazmaier, U. Sakartvelos Mecnierebata Akad. Macne, Kimiis Ser. 2009, 35, 162–166.
Guven, A.; Jones, R. A. Tetrahedron 1993, 49, 11145–11154.
Schwalbe, R.; Steele-Moore, L.; Goodwin, A. C. Antimicrobial Susceptibility Testing Protocols, CRC Press, Boca Raton, FL, USA, 2007.