Kosinostatin, a Quinocycline Antibiotic with Antitumor Activity from Micromonospora sp. TP-A0468

Abstract

Kosinostatin, a quinocycline antibiotic was isolated from the culture broth of an actinomycete strain TP-A0468 along with isoquinocycline B. The producing strain was isolated from the seawater sample collected in Toyama Bay and identified as Micromonospora sp. based on the taxonomic study. Kosinostatin was obtained from the culture fluid by solvent extraction and ODS column chromatography. Kosinostatin inhibited the growth of Gram-positive bacteria strongly (MIC=0.039μg/ml) and Gram-negative bacteria and yeasts moderately (MIC=1.56-12.5μg/ml). It showed cytotoxicity against various cancer cell lines with the IC₅₀ of 0.02-0.6μM and inhibited human DNA topoisomerase IIα with the IC₅₀ of 3-10μM.