Synthesis and Biological Evaluation of 20(S)-Substituted FL118 Conjugates as Novel Antitumor Agents.

ABSTRACT: Fourteen 20(S)-substituted FL118 hybrids coupled with non-steroidal anti-inflammatory drugs (NSAIDs) or amino acids (AA) were synthesized and characterized. Most of them exhibited excellent antitumor activity against the four types of human cancer cell lines (A549, HepG2, HeLa and HCT116). FL118-NSAID derivatives(6a-6d) showed insoluble and lactone increased stability, and could not release FL118 as esterase-triggered prodrugs. FL118-AA (9a-9j) showed better water-soluble and could release the parental compound FL118 as prodrugs in both PBS and human plasma. The antitumor activity in vivo of the FL118-AA 9c, 9i and 9j were consistent with their Topo I inhibitory activity in vitro. The FL118-NSAID 6c could not release FL1

SUBMITTER: Lai J 

PROVIDER: S-EPMC11563187 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature