During a phase I trial of EC145 (a folate-targeted vinca alkaloid conjugate), constipation was identified as the dose-limiting toxicity, probably from a nonfolate receptor-related liver clearance process capable of releasing unconjugated vinca alkaloid from EC145 and shuttling it to the bile. Here, we report on the selective placement of novel carbohydrate segments (1-amino-1-deoxy-glucitolyl-γ...

On direct comparison by TLC and IR we established that the alkaloids A-5 and A-4, first isolated from Vinca herbacea W. K . 1 are identical to the oxindole alkaloid majdine (I), later isolated from Vinca major L. 2' 3 and with its isomer isomajdine (II), prepared by heating of (I) in acetic anhydride 2. Based upon some spectroscopic evidence it was claimed2, that majdine was a diastereomer of c...

Indole ahloids of Vinca species are valued greatly in medical sciences, one reason being for their use as powerful anticancer agents. There are four species of Vinca in Iran: V. rosea, V. major, V. minor and V. herbacea. In previous investigations, we found that these plants have considerable alkaloid similarity (58.8- 75%). Therefore, chromosomic and electrophuretic studies followed after i...

The most commonly reported reason for errors is that a syringe containing a vinca alkaloid is mistaken for a syringe containing an intrathecal medication. Very few medications, including chemotherapeutic agents, can be administered safely into the intrathecal space. Most intrathecal chemotherapy errors involve the accidental injection of vincristine; however, all of the vinca alkaloids (vinblas...

Vinca alkaloids are used extensively in the treatment of childhood acute lymphoblastic leukemia (ALL) and despite their usefulness, drug resistance remains a serious clinical problem. Vinca alkaloids bind to the beta-tubulin subunit of the alpha/beta-tubulin heterodimer and inhibit polymerization of microtubules. Recent studies have implicated altered beta-tubulin isotype expression and mutatio...

In two hamster cell lines that differed 100-fold in their vinblastine sensitivity, dissolution of the mitotic spindle by vinblastine in living cells correlated with cytotoxicity from vinblastine expressed as suppression of colony formation. The effect on the spindle apparatus occurred in 30 sec or less and thus provides a rapid assay for determining the cytotoxic effects of the Vinca alkaloids,...

Naturally occurring vinca alkaloids, vincristine and vinblastine, at micromolar concentrations enhanced the ornithine decarboxylase activity in a dose-response manner in primary cultures of Ehrlich ascites carcinoma cells. After 8 h of culture in the presence or absence of vinblastine, cycloheximide was added to the medium, a 4.5-fold increase in the half-life of the ornithine decarboxylase act...

Vinflunine is a novel Vinca alkaloid presently in Phase I clinical trials. In preclinical studies, it exhibited superior antitumor activity to that of other Vinca alkaloids, including vinorelbine from which it was synthetically derived. Vinca alkaloids appear to inhibit cell proliferation by affecting the dynamics of spindle microtubules. Here we have analyzed the effects of vinflunine and vino...

Vinflunine is a novel Vinca alkaloid presently in Phase I clinical trials. In preclinical studies, it exhibited superior antitumor activity to that of other Vinca alkaloids, including vinorelbine from which it was synthetically derived. Vinca alkaloids appear to inhibit cell proliferation by affecting the dynamics of spindle microtubules. Here we have analyzed the effects of vinflunine and vino...