Re-evaluation of the Fijianolide/Laulimalide Chemotype Suggests an Alternate Mechanism of Action for C-15/C-20 Analogs.

ABSTRACT: Herein, we report on naturally derived microtubule stabilizers with activity against triple negative breast cancer (TNBC) cell lines, including paclitaxel, fijianolide B/laulimalide (3), fijianolide B di-acetate (4), and two new semisynthetic analogs of 3, which include fijianolide J (5) and fijianolide L (6). Similar to paclitaxel, compound 3 demonstrated classic microtubule stabilizing activity with potent (GI₅₀ = 0.7-17 nM) antiproliferative efficacy among the five molecularly distinct TNBC cell lines. Alternatively, compounds 5 or 6, generated from oxidation of C-20 or C-15 and C-20 respectively, resulted in a unique profile with reduced potency (GI₅₀ = 4-9 μM), but improved efficacy in some lines, suggesting

SUBMITTER: Morris JD 

PROVIDER: S-EPMC8928504 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature