Abstract
Epothilones are extremely cytotoxic chemotherapeutic agents with epoxide, thiazole, and ketone groups that share equipotent kinetic similarity with taxol. The in vitro glycosylation catalyzed by uridine diphosphate glucosyltransferase (YjiC) from Bacillus licheniformis generated six novel epothilone A glycoside analouges including epothilone A 7-O-β-D-glucoside, epothilone A 7-O-β-D-galactoside, epothilone A 3,7-O-β-D-digalactoside, epothilone A 7-O-β-D-2-deoxyglucoside, epothilone A 7-O-β-L-rhamnoside, and epothilone A 7-O-β-L-fucoside. Epothilone A 7-O-β-D-glucoside was structurally elucidated by ultra-high performance liquid chromatography-photo diode array (UPLC-PDA) conjugated with high resolution quantitative time-of-flight-electrospray ionization mass spectroscopy (HR-QTOF ESI-MS/MS) supported by one-and two-dimensional nuclear magnetic resonance studies whereas other epothilone A glycosides were characterized by UPLC-PDA and HR-QTOF ESI-MS/MS analyses. The time dependent conversion study of epothilone A to epothilone A 7-O-β-D-glucoside found to be maximum (~26%) between 3 h to 5 h incubation.
Highlights
Epothilones are a class of polypeptide macrolides produced by a few strains of myxo-bacterium such as Sorangium cellulosum (Cheng et al 2008)
Different analogs of epothione (A–H) containing 29 variants have been reported in S. cellulosum but epothilone A and B are the major products with potential applications in therapy and cytotoxic effect in tumor cell lines (Hardt et al 2001)
We explored the macrolide epothilone A, as an aglycon substrate and different nucleotide diphosphate sugars (NDP-D/L-sugars) as sugar donors to generate novel epothilone A glycoside derivatives
Summary
Epothilones are a class of polypeptide macrolides produced by a few strains of myxo-bacterium such as Sorangium cellulosum (Cheng et al 2008). Epothilones were discovered in 1987 as antifungal agents (Hofle and Reichenbach 2005). Different analogs of epothione (A–H) containing 29 variants have been reported in S. cellulosum but epothilone A and B are the major products with potential applications in therapy and cytotoxic effect in tumor cell lines (Hardt et al 2001). 37 natural epothilone variants and related compounds were later isolated and confirmed from the same strain by Hofle and Reichenbach in 2001. Eothilones have been recognized as chemotherapeutic agents against different tumor cell lines including those affected by taxanes with manageable toxicity profiles demonstrated in both preclinical and clinical trials (Lee et al 2001; Thomas et al 2007). Eothilones are potent inducers of a microtubule stabilizing agent, which binds
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