Antitumor properties of novel sesquiterpene lactone analogs as NFκB inhibitors that bind to the IKKβ ubiquitin-like domain (ULD).

ABSTRACT: Melampomagnolide B (MMB, 3) is a parthenolide (PTL, 1) based sesquiterpene lactone that has been used as a template for the synthesis of a plethora of lead anticancer agents owing to its reactive C-10 primary hydroxyl group. Such compounds have been shown to inhibit the IKKβ subunit, preventing phosphorylation of the cytoplasmic IκB inhibitory complex. The present study focuses on the synthesis and in vitro antitumor properties of novel benzyl and phenethyl carbamates of MMB (7a-7k). Screening of these MMB carbamates identified analogs with potent growth inhibition properties against a panel of 60 human cancer cell lines (71% of the molecules screened had GI₅₀ values < 2 μM). Two analogs, the benzyl carbamate 7b and the phenethyl carbamate7k, were the most active compounds. Lead

SUBMITTER: Penthala NR 

PROVIDER: S-EPMC8511328 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature