Received: April 3, 2005 / Accepted: May 24, 2005
© Japan Antibiotics Research Association
Abstract Cytotoxic activities of jadomycin B and five new jadomycin derivatives against four cancer cell lines (HepG2, IM-9, IM-9/Bcl-2 and H460) were evaluated. Jadomycin S was most potent against HepG2, IM-9 and IM-9/Bcl-2 while jadomycin F was most potent against H460. Their potencies correlated with the degrees of apoptosis induced. Structure-activity-relationship analyses clearly demonstrate that the side chains of the oxazolone ring derived from the incorporated amino acids make a significant impact on biological activity. Therefore, jadomycin offers an ideal scaffold to manipulate structure and could be exploited to make many novel bioactive compounds with altered activities.
Keywords jadomycin, derivative, Streptomyces venezuelae, cytotoxic
K.-Q. Yang (Corresponding author), J.-T. Zheng: State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100080, P.R. China and Graduate School of the Chinese Academy of Sciences, E-mail: firstname.lastname@example.org
J. Rohr (Corresponding author), U. Rix: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, Kentucky 40536-0082, U.S.A., E-mail: email@example.com
Q. Chen (Corresponding author), L. Zhao: Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, P.R. China, E-mail: firstname.lastname@example.org
C. Mattingly, V Adamsd: Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, Kentucky 40536-0082, U.S.A.