Syntheses and biological activity of amamistatin B and analogs.
Amamistatins A and B, natural products isolated from a strain of Nocardia, showed growth inhibition against three human tumor cell lines (IC(50) 0.24-0.56 microM). Structurally related mycobactins affect the growth of both mycobacterial and human cells through interference with iron chelation. To further probe the biological activity of this class of compounds, the total syntheses of amamistatin B and two analogs were completed, and the synthetic samples were screened for tumor cell growth inhibition, HDAC inhibition, and Mycobacterium tuberculosis growth inhibition. Amamistatin B (15) and diastereomer 18 were both active against MCF-7 cells (IC(50) 0.12-0.20 microM), and less so against PC-3 cells (IC(50) 8-13 microM). Amamistatin B only moderately inhibited the growth of M. tuberculosis (MIC 47 microM) but showed growth promotion of Mycobacterium smegmatis and other bacteria.
Fennell
Kelley A
KA
Department of Chemistry and Biochemistry and Walther Cancer Center, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Möllmann
Ute
U
Miller
Marvin J
MJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D020128:Inhibitory Concentration 50; D050296:Microbial Viability / Q000187:drug effects; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D009842:Oligopeptides; D010080:Oxazoles; C520142:amamistatin B