Tohoku J. Exp. Med., 2004, 203(1)

Phenoxazine Compounds Produced by the Reactions with Bovine Hemoglobin Show Antimicrobial Activity Against Non-tuberculosis Mycobacteria

SHIGETAKA SHIMIZU, MAMORU SUZUKI, AKIO TOMODA,¹ SADAO ARAI,² HARUHIKO TAGUCHI,³ TOMOKO HANAWA3 AND SHIGERU KAMIYA³

Department of Otorhinolaryngology and Research Institute of Immunological Treatment, Tokyo Medical University, Tokyo 160-0032, ¹Department of Biochemistry and Research Institute of Immunological Treatment, ²Department of Chemistry, Tokyo Medical University, Tokyo 160-0022, and ³Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611

We studied the anti-microbial effects of phenoxazines produced by the reaction of o-aminophenol or its derivatives with bovine hemoglobin, on seven species of mycobacteria such as Mycobacterium tuberculosis, Mycobacterium marinum, Mycobacterium intracellulare, Mycobacterium scrofulaceum, Mycobacterium fortuitum, Mycobacterium kansasii and Mycobacterium smegmatis and some bacteria such as Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica serovar Typhimurium, Staphylococcus aureus, Listeria monocytogeneses. These phenoxazines, including 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxzine-3-one (Phx-1),3-amino-1,4α-dihydro-4α,8-dimethyl-2H-phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3-one (Phx-3), prevented the proliferation of four non-tuberculosis mycobacteria including M. scrofulaceum, M. kansasii, M. marinum, and M. intracellulare dose-dependently, though the inhibitory effects of these phenoxazines differed according to the species of mycobacteria. However these phenoxazines failed to prevent the proliferation of M. tuberculosis, M. fortuitum, and M. smegmatis, and the concerned bacteria other than mycobacteria. The present results may contribute to development of novel antibiotics against non-tuberculolsis mycobacteria.

keywords —— phenoxazines; antimicrobial effects; Mycobacterium

© 2004 Tohoku University Medical Press

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Address for reprints: Akio Tomoda, Department of Biochemistry, Tokyo Medical University, 6-1-1 Shinjuku, Shinkuku-ku, Tokyo 160-0022, Japan.

e-mail: tomoda@tokyo-med.ac.jp

Abbreviations: Phx-1,2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one; Phx-2,3-amino-1,4α-dihydro-4α,8-dimethyl-2H-phenoxazine-2-one; Phx-3,2-aminophenoxazine-3-one; MIC, minimum inhibitory concentration.