Inhibition of platelet aggregation by medermycin and it's related isochromanequinone antibiotics.

During the course of screening inhibitors from microorganisms for platelet aggregation, we found that an isochromanequinone antibiotic medermycin isolated from the cultured broth of Streptomyces sp. KM-1 1749 possessed a potent anti-platelet activity. In this paper, we wish to describe the fermentation, isolation, and in vitro and in vivo anti-platelet activities of medermycin and its related antibiotics such as frenolicins, nanaomycins, kalafungin and mederrhodin. The platelet aggregation inhibitor was screened by incubation of platelet rich plasma (PRP) from rabbit blood with fermentation broth in a 24-well plate using thrombin or adenosine diphosphate (ADP) as a platelet aggregation agent, as reported in a previous paper,1»2) The seed culture of Streptomyces sp. KM-11749 was inoculated in a Sakaguchi flask containing 100 ml of production medium (starch 2.0%, soybean meal 1.0%, NaCl 0.3%, CaCO3 0.3%, pH 7.0 prior to sterilization) and then cultured for 72 hours at 27°C with agitation (250 rpm). The cultured broth (3 liters) was extracted twice with EtOAc. After evaporation of the extract, the residue (190 mg) was chromatographed on a silica gel column (developer: CHC13 MeOH, 50 : 1 to 10 : 1) to obtain a crude powder. The powder