Structures and biological activities of novel 4 '-acetylated analogs of chrysomycins A and B

• Published in: Journal of antibiotics Vol. 70; no. 11; pp. 1078 - 1082
• Main Authors: Wada, Shun-ichi, Sawa, Ryuichi, Iwanami, Fumiki, Nagayoshi, Miho, Kubota, Yumiko, Iijima, Kiyoko, Hayashi, Chigusa, Shibuya, Yuko, Hatano, Masaki, Igarashi, Masayuki, Kawada, Manabu
• Format: Journal Article
• Language: English
• Published: TOKYO Japan Antibiotics Research Assoc 01.11.2017; Nature Publishing Group
• Subjects: Acetylation; Actinomycetes; Aminoglycosides - administration & dosage; Aminoglycosides - chemistry; Aminoglycosides - pharmacology; Analogs; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Anticancer properties; Antiinfectives and antibacterials; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor agents; Bacteria; Biotechnology & Applied Microbiology; Cancer; Cell Line, Tumor; Cytotoxicity; Drug resistance; Gram-positive bacteria; Gram-Positive Bacteria - drug effects; Humans; Immunology; Inhibitory Concentration 50; Life Sciences & Biomedicine; Metabolites; Microbial Sensitivity Tests; Microbiology; Pharmacology & Pharmacy; Physicochemical properties; Science & Technology; Spectrometry; Spectrum Analysis; Toxicity; Tumor cell lines; GILVOCARCIN-V; DNA; VIRENOMYCIN; ELSAMITRUCIN; RAVIDOMYCIN; CHEMISTRY; ANTI-TUMOR ANTIBIOTICS; PHASE-II; ANTITUMOR-ACTIVITY
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/ja.2017.99

Two new 4'-acetylated analogs of chrysomycin were discovered during the screening for antitumor agents from the metabolites of actinomycetes. Their structures and physicochemical properties were determined by standard spectrometric analyses. Their cytotoxicities and antimicrobial activities were evaluated against a panel of cancer cell lines and microbes. While acetylation reinforced the cytotoxicity of chrysomycin B, it weakened the activity of chrysomycin A. Chrysomycin A and its acetylated analog showed high cytotoxicity toward most of the cancer cells with IC(50)s less than 10 ng ml(-1). The 4'-acetyl-chrysomycin A was predominantly observed in nuclei at concentrations where the autofluorescence was observable. Chrysomycins were effective toward Gram-positive bacteria. The 4'-acetylated-chrysomycin A and B had MICs of 0.5-2 mu g ml(-1) and 2 to greater than 64 mu g ml(-1), respectively, toward Gram-positive bacteria including MRSA and VRE.