We recently described a synthesis of 16 desmethyl dihydrodictyostatins and found a few agencies that compared with 6 epi dictyostatin retained nanomolar action in mobile microtubule bundling assays but showed cross resistance to paclitaxel in cells with mutations in beta tubulin. Extending these Icotinib 610798-31-7 studies, we applied the new, very convergent activity to create 6 epi 25,26 dihydrodictyostatin and 25,26 dihydrodictyostatin. Both compounds were effective microtubule perturbing agents that induced mitotic arrest and microtubule assembly in vitro and in whole cells. In vitro radioligand binding studies showed that 25,26 dihydrodictyostatin and its C 6 epimer could displace paclitaxel and epothilone W from microtubules with potencies similar to dictyostatin and discodermolide. Both compounds inhibited the growth of paclitaxel and epothilone W resistant cell lines at reduced nanomolar concentrations, synergized with paclitaxel carcinoid syndrome in MDA MB 231 human breast cancer cells, and had antiangiogenic activity in transgenic zebrafish larvae. The data determine 25,26 dihydrodictyostatin and 6 epi 25,26 dihydrodictyostatin as candidates for scale up further pre-clinical development and synthesis. Microtubules are a vital part in cell division and mitosis. Interference with MT dynamics causes a block in cell cycle progression and ultimately programmed cell death, desirable outcomes for managing rapidly dividing cancer cells. MT perturbing agencies such as taxanes, epothilones, or vinca alkaloids, which stabilize or destabilize MTs, are successfully used in the treatment of stable or hematologic malignancies. The achievements of these anticancer brokers have made MTs one of the most validated molecular cancer targets. Recent, FDA approved MT stabilizing agents would be the taxanes paclitaxel, docetaxel, cabazitaxel, an albumin bound type of paclitaxel, and a semi-synthetic analog of epothilone B, ixabepilone. Despite their success, the development of drug resistance decreases the efficiency Bosutinib ic50 of the agents, resulting in a ongoing attempt to produce novel MT perturbing agents. Many MT stabilizing agents are currently under investigation as potential anticancer therapies. An especially promising adviser, discodermolide, a potent microtubule backing with action superior to paclitaxel, entered into Phase I clinical trials, but disappointingly failed due to pulmonary toxicity. Formerly over-shadowed by discodermolide, dictyostatin, a closely related compound, has gained attention as a possible anti-cancer agent. Ten years after isolation, the complex structure was finally resolved, and two whole syntheses provided enough sample to get a detailed characterization.