Development of New Meridianin/Leucettine-Derived Hybrid Small Molecules as Nanomolar Multi-Kinase Inhibitors with Antitumor Activity.

ABSTRACT: Although the sea ecosystem offers a broad range of bioactivities including anticancer, none of the FDA-approved antiproliferative protein kinase inhibitors are derived from a marine source. In a step to develop new marine-inspired potent kinase inhibitors with antiproliferative activities, a new series of hybrid small molecules (5a-5g) was designed and synthesized based on chemical moieties derived from two marine natural products (Meridianin E and Leucettamine B). Over a panel of 14 cancer-related kinases, a single dose of 10 µM of the parent hybrid 5a possessing the benzo[d][1,3]dioxole moiety of Leucettamine B was able to inhibit the activity of FMS, LCK, LYN, and DAPK1 kinases with 82.5 ± 0.6, 81.4 ± 0.6, 75.2 ± 0.0, and 55 ± 1.1%, respectively. Further optimizatio

SUBMITTER: Elsherbeny MH 

PROVIDER: S-EPMC8468039 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature