Butitaxel analogues: Synthesis and structure-activity relationships

Syed M. Ali, Michael Z. Hoemann, Jeffrey Aubé, Gunda I. Georg, Lester A. Mitscher, Lalith R. Jayasinghe

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

N-Acyl analogues 8, 9, and 12-26 of butitaxel (3) were prepared in one or two steps from amines 5 and 6 through Schotten-Baumann acylation. Seventeen novel analogues, consisting of aliphatic carbamates, alicyclic amides, and heteroaromatic amides, were synthesized. They were evaluated for their in vitro ability to stimulate the formation of microtubules, their cytotoxicity toward B16 melanoma cells, and their solubility in water. The most potent analogue found in this study was N-debenzoyl-N-(2- thenoyl)butitaxel (20), possessing ca. 2-fold better tubulin assembly properties and cytotoxic activity against B16 melanoma cells than paclitaxel. Compound 20 was ca. 25 times more water soluble than paclitaxel.

Original languageEnglish (US)
Pages (from-to)236-241
Number of pages6
JournalJournal of Medicinal Chemistry
Volume40
Issue number2
DOIs
StatePublished - Jan 17 1997

Fingerprint

Dive into the research topics of 'Butitaxel analogues: Synthesis and structure-activity relationships'. Together they form a unique fingerprint.

Cite this