Synthesis and Photophysical Characterization of Fluorescent Naphtho[2,3-<i>d</i>]thiazole-4,9-Diones and Their Antimicrobial Activity against <i>Staphylococcus</i> Strains
Masayori Hagimori,
Fumiko Hara,
Naoko Mizuyama,
Shinya Takada,
Saki Hayashi,
Tamami Haraguchi,
Yoshiro Hatanaka,
Toshihiro Nagao,
Shigemitsu Tanaka,
Miki Yoshii,
Miyako Yoshida
Affiliations
Masayori Hagimori
Department of Analitical Chemistry, Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien 9-Bancho, Nishinomiya City 663-8179, Hyogo, Japan
Fumiko Hara
Department of Analitical Chemistry, Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien 9-Bancho, Nishinomiya City 663-8179, Hyogo, Japan
Naoko Mizuyama
Division of Medical Innovation, Translational Research Center for Medical Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Hyogo, Japan
Shinya Takada
Department of Analitical Chemistry, Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien 9-Bancho, Nishinomiya City 663-8179, Hyogo, Japan
Saki Hayashi
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien 9-Bancho, Nishinomiya City 663-8179, Hyogo, Japan
Tamami Haraguchi
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien 9-Bancho, Nishinomiya City 663-8179, Hyogo, Japan
Yoshiro Hatanaka
Osaka Research Institute of Industrial Science and Technology, 1-6-50 Morinomiya, Joto-ku, Osaka City 536-8553, Osaka, Japan
Toshihiro Nagao
Osaka Research Institute of Industrial Science and Technology, 1-6-50 Morinomiya, Joto-ku, Osaka City 536-8553, Osaka, Japan
Shigemitsu Tanaka
Osaka Research Institute of Industrial Science and Technology, 1-6-50 Morinomiya, Joto-ku, Osaka City 536-8553, Osaka, Japan
Miki Yoshii
Osaka Research Institute of Industrial Science and Technology, 1-6-50 Morinomiya, Joto-ku, Osaka City 536-8553, Osaka, Japan
Miyako Yoshida
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien 9-Bancho, Nishinomiya City 663-8179, Hyogo, Japan
The chemical reaction of 2-(methylsulfinyl)naphtho[2,3-d]thiazole-4,9-dione (3) using different amines, including benzylamine (4a), morpholine (4b), thiomorpholine (4c), piperidine (4d), and 4-methylpiperazine (4e), produced corresponding new tricyclic naphtho[2,3-d]thiazole–4,9–dione compounds (5a–e) in moderate-to-good yields. The photophysical properties and antimicrobial activities of these compounds (5a–e) were then characterized. Owing to the extended π-conjugated system of naphtho[2,3-d]thiazole–4,9–dione skeleton and substituent effect, 5a–e showed fluorescence both in solution and in the solid state. The introduction of nitrogen-containing heterocycles at position 2 of the thiazole ring on naphtho[2,3-d]thiazole-4,9-dione led to large bathochromic shifts in solution, and 5b–e exhibited orange-red fluorescence with emission maxima of over 600 nm in highly polar solvents. Staphylococcus aureus (S. aureus) is a highly pathogenic bacterium, and infection with its antimicrobial-resistant pathogen methicillin-resistant S. aureus (MRSA) results in serious clinical problems. In this study, we also investigated the antimicrobial activities of 5a–e against S. aureus, MRSA, and S. epidermidis. Compounds 5c with thiomorpholine group and 5e with 4-methylpiperazine group showed potent antimicrobial activity against these bacteria. These results will lead to the development of new fluorescent dyes with antimicrobial activity in the future.
