Novel sulfonate Derivatives: potent antimitotic agents

Gwaltney, Stephen L.; Imade, Hovis; Li, Qun; Gehrke, Laura; Credo, R.B.; Warner, Robert B.; Lee, Jang Yun; Kovar, Peter; Frost, David J.; Ng, Shi-Chung; Sham, Hing L.

doi:10.1016/s0960-894x(01)00279-7

Cited by 26 publications

(19 citation statements)

References 8 publications

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“…The antitumor efficacy of ER-34410 (given intravenously at 50 mg/kg) was comparable to that of E7010 (given orally at 400 mg/kg) [6]. Structure-activity relationship studies of these two series of antimitotic sulfonamides (of types 21 and 22, respectively), showed that the para-methoxybenzenesulfonamide moiety was optimal for antitumor activity [6,[38][39][40][41][42][43].…”

Section: E7010/e7070 -Antitumor Sulfonamides In Advanced Clinical Trialsmentioning

confidence: 99%

Anticancer and Antiviral Sulfonamides

Scozzafava

Owa²,

Mastrolorenzo³

et al. 2003

CMC

684

334

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The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti- carbonic anhydrase, diuretic, hypoglycemic and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial antitumor activity in vitro and in vivo. Although they have a common chemical motif of aromatic/heterocyclic or amino acid sulfonamide, there are a variety of mechanisms of their antitumor action, such as carbonic anhydrase inhibition, cell cycle perturbation in the G1 phase, disruption of microtubule assembly, functional suppression of the transcriptional activator NF-Y, and angiogenesis (matrix metalloproteinase, MMP) inhibition among others. Some of these compounds selected via elaborate preclinical screenings or obtained through computer-based drug design, are currently being evaluated in clinical trials. The review summarizes recent classes of sulfonamides and related sulfonyl derivatives disclosed as effective tumor cell growth inhibitors, or for the treatment of different types of cancer. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Thus, at least two clinically used HIV protease inhibitors possess sulfonamide moieties in their molecules, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with less toxicity or activity against drug-resistant viruses. Several non nucleoside HIV reverse transcriptase or HIV integrase inhibitors containing sulfonamido groups were also reported. Another approach to inhibit the growth of retroviruses, including HIV, targets the ejection of zinc ions from critical zinc finger viral proteins, which has as a consequence the inhibition of viral replication in the absence of mutations leading to drug resistance phenotypes. Most compounds with antiviral activity possessing this mechanism of action incorporate in their molecules primary sulfonamide groups. Some small molecule chemokine antagonists acting as HIV entry inhibitors also possess sulfonamide functionalities in their scaffold.

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Section: E7010/e7070 -Antitumor Sulfonamides In Advanced Clinical Trialsmentioning

confidence: 99%

Anticancer and Antiviral Sulfonamides

Scozzafava

Owa²,

Mastrolorenzo³

et al. 2003

CMC

684

334

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“…ABT-751 preferentially binds the b 3 isotype with a Ki of 3.3 μM in a competitive colchicine-binding assay [1,2] and inhibits tubulin polymerization at a similar concentration [3]. Exposure to ABT-751 in vitro leads to a block in the cell cycle at the G2M phase [2], and may result in apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of ABT-751 against childhood cancer models in vivo

et al. 2007

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“…ABT-751 is not a multidrug resistance substrate (12). In preclinical studies, ABT-751 inhibited cellular proliferation of a broad range of human tumor cell lines and xenograft models (9,13), including those that are paclitaxel and doxorubicin resistant due to the multidrug-resistant phenotype.…”

mentioning

confidence: 99%

Phase 1 Study of ABT-751, a Novel Microtubule Inhibitor, in Patients with Refractory Hematologic Malignancies

Yee

Hagey

Verstovšek

et al. 2005

Clinical Cancer Research

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Purpose: ABT-751is anoral antimitotic agent that binds to the colchicine site on h-tubulin. A phase 1study was conducted to determine the maximum tolerated dose and toxicities of ABT-751in patients with advanced myelodysplastic syndrome and relapsed or refractory acute leukemias. Study Design: Thirty-two patients were treated: nine with 100 (n = 3), 125 (n = 3), or 150 mg/m 2 (n = 3) of ABT-751 given orally once daily for 7 days every 3 weeks and 23 with 75 (n = 3), 100 (n = 3), 125 (n = 5), 150 (n = 5), 175 (n = 3), or 200 mg/m 2 (n = 4) of ABT-751 given orally once daily for 21 days every 4 weeks. Consenting patients had pharmacogenetic sampling and enumeration of circulating endothelial cells (CEC). Results: Dose-limiting toxicity consisted of ileus in one patient at 200 mg/m 2 , with a subsequent patient developing grade 2 constipation at the same dose level. One patient with relapsed acute myelogenous leukemia achieved a complete remission that was sustained for 2 months. Four other patients had transient hematologic improvements, consisting of a decrease in peripheral blood blasts and improvements in platelet counts. CEC number was reduced in three patients with a concomitant reduction in peripheral blasts. A previously undescribed nonsynonymous single nucleotide polymorphism, encoding Ala 185

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Novel sulfonate Derivatives: potent antimitotic agents

Cited by 26 publications

References 8 publications

Anticancer and Antiviral Sulfonamides

Anticancer and Antiviral Sulfonamides

Evaluation of ABT-751 against childhood cancer models in vivo

Phase 1 Study of ABT-751, a Novel Microtubule Inhibitor, in Patients with Refractory Hematologic Malignancies

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