Synthesis and biological evaluation of fluorescently labeled epothilone analogs for tubulin binding studies

Ganesh, Thota; Schilling, Jennifer K.; Palakodety, Radha Krishna; Ravindra, Rudravajhala; Shanker, Natasha; Bane, Susan; Kingston, David G. I.

doi:10.1016/j.tet.2003.10.024

Cited by 26 publications

(10 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The diene precursor 7 could be derived from fragments 8 and 9 in a convergent manner. Fragment 8 has previously been synthesized by us employing Nicolaou's method 16 as an intermediate in the synthesis of fluorescently labeled epothilone analogues 17. The alternative diene precursor 10 could be synthesized from fragments 9 and 11 .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Design, synthesis and biological evaluation of bridged epothilone D analogues

et al. 2008

Self Cite

View full text Add to dashboard Cite

Six epothilone D analogues with a bridge between the C4-methyl and the C12-methyl carbons were prepared in an attempt to constrain epothilone D to its proposed tubulin-binding conformation. Ring-closing metathesis (RCM) was employed as the key step to build the C4-C26 bridge. In antiproliferative assays in the human ovarian cancer (A2780) and prostate cancer (PC3) cell lines, and also in tubulin assembly assay, all these compounds proved to be less active than epothilone D.

show abstract

Section: Resultsmentioning

confidence: 99%

“…The synthesis of fragment 8 was carried out as previously described 16,17. Ketone 9 was prepared as shown in Scheme 2.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis and biological evaluation of bridged epothilone D analogues

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…Whereas β-epoxides and their analogs are entirely inactive, inversion of the configuration only at C12, corresponding to a C12, C13-trans configuration, retains activity. 180 Last but not least, replacement of the lactone group of epothilone B, D, and F by a lactam reduces cytotoxic activity and tubulin binding slightly, while other properties such as the therapeutic window or p.o. 4,108,109 The C12 methyl is extremely important for high activity of the epothilone B series.…”

Section: Structure-activity Relationshipsmentioning

confidence: 99%

Epothilone, a Myxobacterial Metabolite with Promising Antitumor Activity

Reichenbach¹,

Höfle²

2005

Anticancer Agents From Natural Products

View full text Add to dashboard Cite

“…The synthesis of the labeled epothilone D analog 11 was achieved as shown in Scheme . The advanced precursor 8 , prepared by a known macrolactonization strategy, was used as the starting material. Stannane 9 was prepared from 2,4‐dibromothiazole by the two‐step procedure described previously, substituting trideuteromethyl triflate for the methyl triflate used previously .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of isotopically labeled epothilones

Ganesh

Brodie

Banerjee

et al. 2013

Labelled Comp Radiopharmac

Self Cite

View full text Add to dashboard Cite

The epothilones, including epothilones B and D, are macrocyclic lactones which have potent cytotoxicities and which promote the polymerization of tubulin to mictotubules by binding to and stabilizing the tubulin polymer. They have a very similar mechanism of action to paclitaxel (Taxol®). The determination of the microtubule-binding conformation of the epothilones is an important piece of information in designing improved analogs for possible clinical use, and internuclear distance information that will assist the determination of this conformation can be obtained by REDOR NMR studies of microtubule-bound epothilones with appropriate stable isotope labels. Analogs of epothilone B and epothilone D with [2H3] and [19F] labels were prepared from an advanced precursor for potential use in REDOR NMR studies to determine internuclear distances in tubulin-bound ligand.

show abstract

Synthesis and biological evaluation of fluorescently labeled epothilone analogs for tubulin binding studies

Cited by 26 publications

References 22 publications

Design, synthesis and biological evaluation of bridged epothilone D analogues

Design, synthesis and biological evaluation of bridged epothilone D analogues

Epothilone, a Myxobacterial Metabolite with Promising Antitumor Activity

Synthesis of isotopically labeled epothilones

Contact Info

Product

Resources

About