Synthesis, antibacterial and antifungal activities of some carbazole derivatives

Moellering, 2007, Am. J. Med., 120, 4, 10.1016/j.amjmed.2007.04.001 Morin, 2005, Macromol. Rapid. Commun., 26, 761, 10.1002/marc.200500096 Kim, 2007, Tetrahedron, 63, 1913, 10.1016/j.tet.2006.12.082 Zhou, 2009, Sci. China, Ser. B, 52, 415, 10.1007/s11426-009-0103-2 Zhou, 2009, Sci. China, Ser. B, 39, 208 Knölker, 2002, Chem. Rev., 102, 4303, 10.1021/cr020059j Knölker, 2003, Eur. J. Org. Chem., 4, 740, 10.1002/ejoc.200390116 Hagiwara, 2000, Tetrahedron, 56, 5807, 10.1016/S0040-4020(00)00543-3 Cuong, 2008, Nat. Prod. Res., 22, 1428, 10.1080/14786410802006033 Rajakumar, 2009, Eur. J. Med. Chem., 44, 3040, 10.1016/j.ejmech.2008.07.031 Rajakumar, 2008, Bioorg. Med. Chem. Lett., 18, 4416, 10.1016/j.bmcl.2008.06.047 Mi, 2007, Chin. J. Antibiot., 32, 587 Cai, 2009, Chin. J. New Drugs, 18, 598 Bai, 2007, Chem. Res. Appl., 19, 721 Güven, 2007, Bioorg. Med. Chem. Lett., 17, 2233, 10.1016/j.bmcl.2007.01.061 Luo, 2009, Arch. Pharm. Chem. Life Sci., 342, 386, 10.1002/ardp.200800221 Muroi, 2004, Bioorg. Med. Chem., 12, 583, 10.1016/j.bmc.2003.10.046 (a) Kadi, A. A.; El-Brollosy, N. R.; Al-Deeb, O. A.; Habib, E. E.; Ibrahim, T. M.; El-Emam, A. A. Eur. J. Med. Chem. 2007, 42, 235; (b) Özbek, N.; Katırcıoğlu, H.; Karacan, N.; Baykal, T. Bioorg. Med. Chem. 2007, 15, 5105. Experimental determination of antibacterial and antifungal activities. The minimal inhibitory concentrations (MICs) of the title compounds were determined in vitro by the modified microbroth dilution method according to the methods defined by the National Committee for Clinical Laboratory Standards. The test strains were provided by the School of Pharmaceutical Sciences, Southwest University. Fluconazole and chloramphenicol obtained from their respective manufacturers served as controls. The prepared compounds 1–5 were evaluated for their antibacterial activity against S. aureus ATCC 29213, MRSA N 315 and B. subtilis ATCC 21216 as Gram-positive, E. coli ATCC 25922, P. aeruginosa ATCC 27853 and B. proteus ATCC 49027 as Gram-negative bacteria. The bacterial suspension was adjusted with sterile saline to a concentration of 1×105 CFU. The test compounds were dissolved in dimethyl sulfoxide (DMSO) to prepare the stock solutions. The test compounds and reference drugs were prepared in Mueller–Hinton broth (Guangdong huaikai microbial sci. & tech co., Ltd, Guangzhou, Guangdong, China) by twofold serial dilution to obtain the required concentrations of 512, 256, 128, 64, 32, 16, 8, 4, 2, 1, 0.5μg/mL. These dilutions were inoculated and incubated at 37°C for 24h. To ensure that the solvent had no effect on bacterial growth, a control test was performed with test medium supplemented with DMSO at the same dilutions as used in the experiment. The new compounds were evaluated for their antifungal activity against C. albicans ATCC 76615 and A. fumigatus ATCC 96918. A spore suspension in sterile distilled water was prepared from 1-day old culture of the fungi growing on Sabouraud agar (SA) media. The final spore concentration was 1−5×103sporemL−1. From the stock solutions of the tested compounds and reference antifungal fluconazole, dilutions in sterile RPMI 1640 medium (Neuronbc Laboraton Technology CO., Ltd, Beijing, China) were made resulting in eleven wanted concentrations (0.5–512μg/mL) of each tested compound. These dilutions were inoculated and incubated at 35°C for 24h. The drug MIC50 was defined as the first well with an approximate 50% reduction in growth compared to the growth of the drug-free well. The minimum inhibitory concentration (MIC50) values (in μg/mL) were summarized in Table 1. Yun, 2003, J. Org. Chem., 68, 2467, 10.1021/jo0263519 Chang, 2004, Anal. Chem., 76, 4490, 10.1021/ac049510s