Synthesis of new carbon‐11‐labeled 7‐aroyl‐aminoindoline‐1‐sulfonamides as potential PET agents for imaging of tubulin polymerization in cancers

Wang, Min; Gao, Mingzhang; Miller, Kathy D.; Sledge, George W.; Hutchins, Gary D.; Zheng, Qi‐Huang

doi:10.1002/jlcr.1462

Cited by 14 publications

(3 citation statements)

References 19 publications

(13 reference statements)

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“…The two most potent compounds (Figure ), J30 and its counterpart with a 2‐furyl ring, displayed strong cytotoxic activity, even against MDR‐overexpressing cell lines, and vascular disrupting activity due to binding at the colchicine site (TPI IC 50 is 1.1 µM) . In addition, J30 has potential as PET probe and MPT0B271 has shown an additional mechanism of action through STAT3 phosphorylation inhibition …”

Section: The Sulfonamidesmentioning

confidence: 99%

Antitubulin sulfonamides: The successful combination of an established drug class and a multifaceted target

Vicente‐Blázquez

González

Álvarez

et al. 2018

Medicinal Research Reviews

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Tubulin, the microtubules and their dynamic behavior are amongst the most successful antitumor, antifungal, antiparasitic, and herbicidal drug targets. Sulfonamides are exemplary drugs with applications in the clinic, in veterinary and in the agrochemical industry. This review summarizes the actual state and recent progress of both fields looking from the double point of view of the target and its drugs, with special focus onto the structural aspects. The article starts with a brief description of tubulin structure and its dynamic assembly and disassembly into microtubules and other polymers. Posttranslational modifications and the many cellular means of regulating and modulating tubulin's biology are briefly presented in the tubulin code. Next, the structurally characterized drug binding sites, their occupying drugs and the effects they induce are described, emphasizing on the structural requirements for high potency, selectivity, and low toxicity. The second part starts with a summary of the favorable and highly tunable combination of physical-chemical and biological properties that render sulfonamides a prototypical example of privileged scaffolds with representatives in many therapeutic areas. A complete description of tubulin-binding sulfonamides is provided, covering the different species and drug sites. Some of the antimitotic sulfonamides have met with very successful Med Res Rev. 2019;39:775-830. wileyonlinelibrary.com/journal/med © 2018 Wiley Periodicals, Inc. | 775applications and others less so, thus illustrating the advances, limitations, and future perspectives of the field.All of them combine in a mechanism of action and a clinical outcome that conform efficient drugs. K E Y W O R D S molecular mechanisms, sulfonamides, tubulin binding drugs, tubulin binding sites 1 | INTRODUCTION Drugs targeting tubulin and the microtubules (tubulin binding drugs [TBDs]) are amongst the most successful antitumor, antifungal, antiparasitic, and herbicidal agents with applications in the clinic, in veterinary and in the agrochemical industry. Recently, the combination of computational methods, medicinal chemistry, biochemistry, structural biology, and cell biology is starting to unravel the intricacies of tubulin binding drugs and of the microtubules themselves, thus paving the way towards new and better TBDs. New methodological advances such as the high resolution cryo-electron microscopy, the imaging of individual microtubule dynamics, and the achievement of recombinant tubulin, altogether with more established methodologies for the study of the microtubules have combined to provide a sharper view of the structure and function of these essential cell components and their interactions with clinically important drugs. The sulfonamides are a prototypical example of privileged scaffolds, with representatives in many therapeutic areas, due to a combination of favorable and highly tunable physical-chemical and biological properties. The early discovery of the dinitroaniline herbicides, and mainly the seminal discovery o...

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Section: The Sulfonamidesmentioning

confidence: 99%

Antitubulin sulfonamides: The successful combination of an established drug class and a multifaceted target

Vicente‐Blázquez

González

Álvarez

et al. 2018

Medicinal Research Reviews

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“…The mini-PEG approach has recently been shown to separate dye and ligand sufficiently for preserved receptor affinity. , Our first approach to modify ligand 5 is outlined in Scheme . 4-(Benzyloxy)benzenesulfonyl chloride was synthesized from commercially available sodium-4-hydroxybenzenesulfonate 6 in two steps, as reported by Wang et al, in 72% overall yield. The resulting arylsulfonyl chloride 8 was coupled with N -β-Boc- l -2,3-diaminopropionic acid methyl ester 9 to yield compound 10 .…”

Section: Resultsmentioning

confidence: 99%

Fluorescent Non-peptidic RGD Mimetics with High Selectivity for α_Vβ₃vs α_IIbβ₃Integrin Receptor: Novel Probes for in Vivo Optical Imaging

Alsibai¹,

Hahnenkamp²,

Eisenblätter

et al. 2014

J. Med. Chem.

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Integrins are heterodimeric transmembrane protein receptors consisting of different α and β subunits. α(v)β(3) integrins are overexpressed on many tumor cells and tumor-associated angiogenic vessels, whereas α(IIb)β(3) is a receptor for, e.g., fibrinogen and mediates platelet aggregation. In this study, a near-infrared fluorescent imaging probe has been designed and synthesized by conjugating fluorescent dyes to a non-peptidic, pharmacophore-based ligand, based on a molecular modeling design approach. Affinity values were determined, and in vitro cell binding assays and preliminary in vivo xenograft studies in nude mice were performed to evaluate target binding. Competition assays revealed excellent binding and selectivity to α(v)β(3) compared to that for α(IIb)β(3). In vitro, the probe showed high target binding on α(v)β(3)-positive M-21 cells and negligible binding to α(v)β(3)-negative MCF-7 cells. In vivo, the tracer is able to image target expression in U-87 xenografts with a maximum signal-to-noise ratio (SNR) of 2.5:1 at 24 h after injection.

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“…Using protic acid (HBr) instead of the literature method Lewis acid (BBr 3 ) 1 as the desmethylating reagent, it significantly improved the yield of desmethylation reaction, because protic acid promoted the desmethylation reaction of phenolic methoxy aminoalkylindole derivatives to easily form phenolic hydroxyl precursor and CH 3 Br. 17,18 As shown in Scheme 2, the reduction of compound 3 with LiAlH 4 gave the standard 5 in 49% yield. Careful workup by adjusting appropriate pH to 5 improved the yield of the reduction from 18% to 49%.…”

mentioning

confidence: 98%

Synthesis of carbon-11-labeled aminoalkylindole derivatives as new candidates of cannabinoid receptor radioligands for PET imaging of alcohol abuse

Gao

Wang

et al. 2014

Bioorganic & Medicinal Chemistry Letters

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Synthesis of new carbon‐11‐labeled 7‐aroyl‐aminoindoline‐1‐sulfonamides as potential PET agents for imaging of tubulin polymerization in cancers

Cited by 14 publications

References 19 publications

Antitubulin sulfonamides: The successful combination of an established drug class and a multifaceted target

Antitubulin sulfonamides: The successful combination of an established drug class and a multifaceted target

Fluorescent Non-peptidic RGD Mimetics with High Selectivity for α_Vβ₃vs α_IIbβ₃Integrin Receptor: Novel Probes for in Vivo Optical Imaging

Synthesis of carbon-11-labeled aminoalkylindole derivatives as new candidates of cannabinoid receptor radioligands for PET imaging of alcohol abuse

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Synthesis of new carbon‐11‐labeled 7‐aroyl‐aminoindoline‐1‐sulfonamides as potential PET agents for imaging of tubulin polymerization in cancers

Cited by 14 publications

References 19 publications

Antitubulin sulfonamides: The successful combination of an established drug class and a multifaceted target

Antitubulin sulfonamides: The successful combination of an established drug class and a multifaceted target

Fluorescent Non-peptidic RGD Mimetics with High Selectivity for αVβ3vs αIIbβ3Integrin Receptor: Novel Probes for in Vivo Optical Imaging

Synthesis of carbon-11-labeled aminoalkylindole derivatives as new candidates of cannabinoid receptor radioligands for PET imaging of alcohol abuse

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Fluorescent Non-peptidic RGD Mimetics with High Selectivity for α_Vβ₃vs α_IIbβ₃Integrin Receptor: Novel Probes for in Vivo Optical Imaging