Discovery of Novel 2‐<i>N</i>‐Aryl‐Substituted Benzenesulfonamidoacetamides: Orally Bioavailable Tubulin Polymerization Inhibitors with Marked Antitumor Activities

Liu, Zulong; Zhou, Zuyu; Tian, Wei; Fan, Xing; Duan, Xue; Yu, Liping; Yu, Qiang; Long, Ya‐Qiu

doi:10.1002/cmdc.201100529

Cited by 17 publications

(10 citation statements)

References 36 publications

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“…Changes in the mechanism of action have also been observed for less‐potent series . Larger more polar substitutions showed reduced potencies …”

Section: The Sulfonamidesmentioning

confidence: 87%

“…Bridge reversal has modest effects but sulfonamide nitrogen methylation enhances potency . Simultaneous removal of the methoxy groups on both rings results in dramatic potency losses . Replacement of the hydroxy group at the 3 position of the B ring by an amino group maintains the potency, but substitution of the p‐ methoxy group by methyl, amino, or acetamido groups decreases cytotoxicity .…”

Section: The Sulfonamidesmentioning

confidence: 99%

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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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“…Changes in the mechanism of action have also been observed for less‐potent series . Larger more polar substitutions showed reduced potencies …”

Section: The Sulfonamidesmentioning

confidence: 87%

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 acetamide functional group is responsible for antimicrobial [25, 26], antioxidant [27, 28], narcolepsy treatment [29], anti-inflammatory [30, 31], platelet aggregation inhibitory [32], and urease inhibitory activities [33]. The acetamides and their analogues are also well studied as chemotherapeutic agents [34, 35].…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and biological evaluation of novel N4-substituted sulfonamides: acetamides derivatives as dihydrofolate reductase (DHFR) inhibitors

et al. 2019

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Background Sulfonamide derivatives are of great attention due to their wide spectrum of biological activities. Sulfonamides conjugated with acetamide fragments exhibit antimicrobial and anticancer activities. The inhibition dihydrofolate reductase (DHFR) is considered as one of the most prominent mechanism though which sulfonamide derivatives exhibits antimicrobial and antitumor activities. Results In this study, a new series of 2-(arylamino)acetamides and N -arylacetamides containing sulfonamide moieties were designed, synthesized, characterized and assessed for their antimicrobial activity and screened for cytotoxic activity against human lung carcinoma (A-549) and human breast carcinoma (MCF-7) cell lines. A molecular docking study was performed to identify the mode of action of the synthesized compounds and their good binding interactions were observed with the active sites of dihydrofolate reductase (DHFR). Conclusion Most of the synthesized compounds showed significant activity against A-549 and MCF-7 when compared to 5-Fluorouracil (5-FU), which was used as a reference drug. Some of these synthesized compounds are active as antibacterial and antifungal agents. Electronic supplementary material The online version of this article (10.1186/s13065-019-0603-x) contains supplementary material, which is available to authorized users.

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“…[24][25][26] Research efforts have been directed towards the development analogues of E7010 as inhibitors of tubulin polymerization in cancer drug discovery programs. [27][28] …”

mentioning

confidence: 98%

Design and synthesis of cis-restricted benzimidazole and benzothiazole mimics of combretastatin A-4 as antimitotic agents with apoptosis inducing ability

Ashraf

Shaik

Malik

et al. 2016

Bioorganic & Medicinal Chemistry Letters

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Discovery of Novel 2‐N‐Aryl‐Substituted Benzenesulfonamidoacetamides: Orally Bioavailable Tubulin Polymerization Inhibitors with Marked Antitumor Activities

Cited by 17 publications

References 36 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

Design, synthesis, and biological evaluation of novel N4-substituted sulfonamides: acetamides derivatives as dihydrofolate reductase (DHFR) inhibitors

Design and synthesis of cis-restricted benzimidazole and benzothiazole mimics of combretastatin A-4 as antimitotic agents with apoptosis inducing ability

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