Lipase-catalyzed preparation of chromomycin A₃ analogues and biological evaluation for anticancer activity.
Several acyl derivatives of the aureolic acid chromomycin A(3) were obtained via lipase-catalyzed acylation. Lipase B from Candida antarctica (CAL-B) was found to be the only active biocatalyst, directing the acylation regioselectively towards the terminal secondary hydroxyl group of the aglycone side chain. All new chromomycin A(3) derivatives showed antitumor activity at the micromolar or lower level concentration. Particularly, chromomycin A(3) 4'-vinyladipate showed 3-5 times higher activity against the four tumor cell lines assayed as compared to chromomycin A(3).
Entrechem, SL, Edificio Científico Tecnológico, Campus El Cristo, Oviedo 33006, Spain.
Javier
J
González-Sabín
Luz Elena
LE
Núñez
Nuria
N
Menéndez
Alfredo F
AF
Braña
Carmen
C
Méndez
José A
JA
Salas
Vicente
V
Gotor
Francisco
F
Morís
D000215:Acylation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D055162:Biocatalysis; D002175:Candida / Q000201:enzymology; D045744:Cell Line, Tumor; D014128:Chromomycin A3 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008049:Lipase / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D014128:Chromomycin A3; D008049:Lipase