Novel sulfonate analogues of combretastatin A-4

Gwaltney, Stephen L.; Imade, Hovis; Barr, Kenneth J.; Li, Qun; Gehrke, Laura; Credo, R.B.; Warner, Robert B.; Lee, Jang Yun; Kovar, Peter; Wang, Jieyi; Nukkala, Michael A.; Zielinski, Nicolette A.; Frost, David J.; Ng, Shi Chung; Sham, Hing L.

doi:10.1016/s0960-894x(01)00098-1

Cited by 53 publications

(31 citation statements)

References 17 publications

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“…It shows potent cytotoxicity against a broad spectrum of human cancer cell lines, including those of MDR-positive lines (9). CA-4P (disodium combretastatin-A-4 -3-O-phosphate), a water-soluble prodrug, is a novel antitumor vascular targeting agent and is the first combretastatin analog to enter clinic trials (10,11).…”

Section: Introductionmentioning

confidence: 99%

BPR0L075, a Novel Synthetic Indole Compound with Antimitotic Activity in Human Cancer Cells, Exerts Effective Antitumoral Activityin Vivo

Kuo¹,

Hsieh

Pan³

et al. 2004

Cancer Research

195

187

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Section: Introductionmentioning

confidence: 99%

BPR0L075, a Novel Synthetic Indole Compound with Antimitotic Activity in Human Cancer Cells, Exerts Effective Antitumoral Activityin Vivo

Kuo¹,

Hsieh

Pan³

et al. 2004

Cancer Research

195

187

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“…Previous studies showed that sulfonate analogues of CA-4 bind to the colchicine binding domain of tubulin. [26] In contrast, the compounds synthesized in this study bind to the vinblastine, but not the colchicines, domain. Among known tubulin polymerization inhibitors, vinblastine and colchicine binding sites, as well as their mechanisms of action of these compound, have been studied thoroughly.…”

Section: Discussionmentioning

confidence: 59%

“…Among antimitotic CA-4 analogues, Gwaltney et al [26] synthesized a series of CA-4-like sulfonates by introducing a sulfonate functional group as a tether between the two aryl rings (3-5, Figure 1), which are structural features of CA-4. Many of the sulfonates were reported to have excellent antitumor activities as well as inhibitory effects against tubulin polymerization.…”

Section: Introductionmentioning

confidence: 99%

Novel 2‐Substituted Quinolin‐4‐yl‐benzenesulfonate Derivatives: Synthesis, Antiproliferative Activity, and Inhibition of Cellular Tubulin Polymerization

Kakadiya¹,

Wu²,

Dong³

et al. 2011

ChemMedChem

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A series of 2-substituted quinolin-4-yl-benzenesulfonate derivatives were synthesized for the purpose of evaluating antiproliferative activity. Structure-activity relationships of the newly synthesized compounds against human lymphoblastic leukemia and various solid tumor cell growths in culture are discussed. Of these derivatives, 2-phenyl-6-pyrrolidinyl-4-quinoline sulfonate analogues 10 f, 10 g, and 10 k, and 4'-nitrophenyl sulfonate 10 m exhibit superior cytotoxicity over other sulfonates. The antiproliferative activities of these compounds correlate well with their abilities to induce mitotic arrest and apoptosis. Mechanistic studies indicate that they target the vinblastine binding site of tubulin and inhibit cellular tubulin polymerization. Hence, these compounds induce the formation of aberrant mitotic spindles and mitotic arrest, resulting in intensive apoptosis. The tested compounds were shown to be poor substrates for membrane multidrug resistance transporters. The present studies suggest that these newly synthesized compounds are promising tubulin polymerization inhibitors and are worthy of further investigation as antitumor agents.

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“…P-gp is the most characterized member of the ABC family. It is well established from numerous sources that the combretastatins are not substrates for the P-gp and thus offer a therapeutic advantage over other clinically used MTAs such as the taxanes and the vinca alkaloids, which are known P-gp substrates (Shirai et al, 1998;Gwaltney et al, 2001;Xu et al, 2008;Greene et al, 2010;Lee et al, 2010;Romagnoli et al, 2012;Penthala et al, 2013). Similarly, the combretastatins demonstrated potent activity in cancer cells overexpressing BCRP .…”

Section: Cell Survival/resistancementioning

confidence: 99%

Combretastatins: More Than Just Vascular Targeting Agents?

Greene

Meegan

Zisterer

2015

J Pharmacol Exp Ther

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Several prodrugs of the naturally occurring combretastatins have undergone extensive clinical evaluation as vascular targeting agents (VTAs). Their increased selectivity toward endothelial cells together with their innate ability to rapidly induce vascular shutdown and inhibit tumor growth at doses up to 10-fold less than the maximum tolerated dose led to the clinical evaluation of combretastatins as VTAs. Tubulin is well established as the molecular target of the combretastatins and the vast majority of its synthetic derivatives. Furthermore, tubulin is a highly validated molecular target of many direct anticancer agents routinely used as front-line chemotherapeutics. The unique vascular targeting properties of the combretastatins have somewhat overshadowed their development as direct anticancer agents and the delineation of the various cell death pathways and anticancer properties associated with such chemotherapeutics. Moreover, the ongoing clinical trial of OXi4503 (combretastatin-A1 diphosphate) together with preliminary preclinical evaluation for the treatment of refractory acute myelogenous leukemia has successfully highlighted both the indirect and direct anticancer properties of combretastatins. In this review, we discuss the development of the combretastatins from nature to the clinic. The various mechanisms underlying combretastatin-induced cell cycle arrest, mitotic catastrophe, cell death, and survival are also reviewed in an attempt to further enhance the clinical prospects of this unique class of VTAs.

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Novel sulfonate analogues of combretastatin A-4

Cited by 53 publications

References 17 publications

BPR0L075, a Novel Synthetic Indole Compound with Antimitotic Activity in Human Cancer Cells, Exerts Effective Antitumoral Activityin Vivo

BPR0L075, a Novel Synthetic Indole Compound with Antimitotic Activity in Human Cancer Cells, Exerts Effective Antitumoral Activityin Vivo

Novel 2‐Substituted Quinolin‐4‐yl‐benzenesulfonate Derivatives: Synthesis, Antiproliferative Activity, and Inhibition of Cellular Tubulin Polymerization

Combretastatins: More Than Just Vascular Targeting Agents?

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