Cytotoxic activities of new jadomycin derivatives.
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.
Zheng
Jian-Ting
JT
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100080, PR. China.
Rix
Uwe
U
Zhao
Lixia
L
Mattingly
Cynthia
C
Adams
Val
V
Chen
Quan
Q
Rohr
Jürgen
J
Yang
Ke-Qian
KQ
D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000633:toxicity; D013302:Streptomyces / Q000187:drug effects; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D007546:Isoquinolines; C081750:jadomycin B