Jute (Corchorus olitorius) endophytic fungi Grammothele lineata SDL-CO-2015-1 was found to produce epothilone B, a well-reported anticancer compound. Both the genome and RNA-seq data of G. revealed presence gene clusters. In silico mining using NaPDoS (Natural Product Domain Seeker) identified four genes matching with cluster (Epo D). Epothilone extracted from extracellular extract this fungus ...

An unusual reaction with Grubbs' catalyst during the synthesis of bridged epothilones yielded five-membered internal lactones instead of the expected metathesis products. Three of the lactones have activities comparable to epothilone D.

The epothilones are macrolide compounds that have been shown to stabilize microtubules. The epothilones are strong promoters of tubulin polymerization in vitro and have significant antitumor activity against human cancer cells that are taxane resistant, express the multidrug resistance gene MDR-1 (ABCB1), and have acquired tubulin mutations. Several epothilones have been evaluated in clinical t...

Although microtubule interacting agents inhibit spindle dynamics, thereby leading to a block in mitosis, we report that low concentrations of these drugs result in differential mitotic effects. Microtubule-stabilizing agents including Taxol, epothilone B, and discodermolide produce aneuploid populations of A549 cells in the absence of a mitotic block. Such aneuploid populations are diminished i...

BMS-247550 is a methyl, semi-synthetic analog of the natural product epothilone B. Provided to the National Cancer Institute (NCI) by Bristol-Myers Squibb, BMS-247550 was chosen for clinical development because it demonstrated antitumor activity in paclitaxel (Taxol)-sensitive, paclitaxel-insensitive, and paclitaxel-resistant human tumor models. The first NCI-sponsored clinical trial of BMS-247...

Microtubules (MTs) are cytoskeletal components whose structural integrity is mandatory for the execution of many basic cell functions. Utilizing parental and drug-resistant ovarian carcinoma cell lines that have acquired point mutations in -tubulin and p53, we studied the level of expression and modification of proteins involved in apoptosis and MT integrity. Extending previous results, we demo...