土壌微生物代謝産物からの細胞接着阻害物質の探索 Research of macrosphelide, a novel inhibitor of cell-cell adhesion molecule, from microbial orgainisms in soil
Potent anti-adherent activity was detected in fermentation extracts of microbial strain FO-5050. Active compounds designated macrosphelide A, B was isolated and determined to be 16-membered macrolide antibiotics possessing three ester bonds in the ring structure. Macrosphelide A dose-dependently inhibited the adhesion of HL-60 cells to LPS-activated HUVEC monolayer (IC<SUB>50</SUB>, 2.5 μM); macrosphelide B also inhibited HL-60 adhesion but to a lesser extent (IC<SUB>50</SUB>, 36 μM). Macrosphelide A showed no any antimicrobial and cytocidal activities at the concentration of 1000 μg/ml and 100 μg/ml, respectively.<BR> Macrosphelide is the newly discovered anti-cell adhesion substance, which is, but not peptide or antibody, a low molecular weight and unique 16-membered macrolide antibiotics possessing three ester bonds. Therefore, it is of interest to examine the mode of action of macrosphelide inhibiting cell-cell adhesion molecule and the availability for the therapy against refractory disease such as tumor invasion and metastasis or chronic inflammatory disease.
日本薬理学雑誌 106, 143-146, 1995-09-01