Identification of a melampomagnolide B analog as a potential lead molecule for treatment of acute myelogenous leukemia.

ABSTRACT: A series of carbamate derivatives of the antileukemic sesquiterpene melampomagnolide B (MMB) has been synthesized utilizing a 1,2,4-triazole carbamate conjugate of MMB as an intermediate synthon. Five imidazole- and benzimidazole-carbamate analogs of MMB (8a-8e) were prepared and evaluated for anti-leukemic activity against cultured M9 ENL1 AML cells. All the analogs exhibited improved anti-leukemic activity (EC₅₀=0.90-3.93μM) when compared to parthenolide and the parent sesquiterpene, MMB (EC₅₀=7.0μM and 15.5μM, respectively). The imidazole carbamate analog, 8a (EC₅₀=0.9μM), was 16 times more potent than MMB. The comparative bioavailabilities of 8a and MMB were determined in BALB/c mice following oral dosing of these compounds. It has been demonstrated tha

SUBMITTER: Albayati ZAF 

PROVIDER: S-EPMC5291787 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature