Discovery of 4-Amino and 4-Hydroxy-1-aroylindoles as Potent Tubulin Polymerization Inhibitors

Liou, Jing Ping; Wu, Zi Yi; Kuo, Ching Chuan; Chang, Chin-Chih; Lu, Pei Yi; Chen, Chi Ming; Hsieh, Hsing Pang; Chang, Jang Yang

doi:10.1021/jm800150d

Cited by 66 publications

(31 citation statements)

References 33 publications

(21 reference statements)

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“…1-Aroylindole, 1-aroylindoline, 1-aroyl-1,2,3,4-tetrahydroquinoline, and 2-, 3-, 4-, 5-, 6-, 7-, 8-aroylquinolines were synthesized and evaluated for anticancer activity as CA-4 derivatives (82,83). Among these substituents, 1-aroylindoles with C4-amino ( 85 ) and C4-hydroxy ( 86 ) substituents exhibited antitubulin activity superior or comparable to that of colchicine and CA-4 with IC 50 values of 0.9 and 0.6 μM, respectively.…”

Section: Reported Cbsi In Preclinical Studiesmentioning

confidence: 99%

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

et al. 2012

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Tubulin dynamics is a promising target for new chemotherapeutic agents. The colchicine binding site is one of the most important pockets for potential tubulin polymerization destabilizers. Colchicine binding site inhibitors (CBSI) exert their biological effects by inhibiting tubulin assembly and suppressing microtubule formation. A large number of molecules interacting with the colchicine binding site have been designed and synthesized with significant structural diversity. CBSIs have been modified as to chemical structure as well as pharmacokinetic properties, and tested in order to find a highly potent, low toxicity agent for treatment of cancers. CBSIs are believed to act by a common mechanism via binding to the colchicine site on tubulin. The present review is a synopsis of compounds that have been reported in the past decade that have provided an increase in our understanding of the actions of CBSIs.

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Section: Reported Cbsi In Preclinical Studiesmentioning

confidence: 99%

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

et al. 2012

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“…Helquinoline is a potent tetrahydroquinoline-derived antibiotic that has been extracted from Janibecter limosus [47]. In particular, tetrahydroquinoline exhibits a wide range of biological activities, for example, anti-HIV [48], antitrypanosomal [49], psychotropic [50], anti-inflammatory [51], antibacterial [52], antimalarial [53], antifungal [54] and antitumor activities [55]. The incorporation of a functional group into a pharmacophore is an attractive approach to the design and synthesis of new bioactive compounds.…”

Section: Introductionmentioning

confidence: 99%

One-Pot Multicomponent Synthesis and Bioevaluation of Tetrahydroquinoline Derivatives as Potential Antioxidants, α-Amylase Enzyme Inhibitors, Anti-Cancerous and Anti-Inflammatory Agents

et al. 2020

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Mankind has always suffered from multiple diseases. Therefore, there has been a rigorous need in the field of medicinal chemistry for the design and discovery of new and potent molecular entities. In this work, thirteen tetrahydroquinoline derivatives were synthesized and evaluated biologically for their antioxidant, α-amylase enzyme inhibitory, anti-proliferative and anti-inflammatory activities. SF8 showed the lowest IC50 of 29.19 ± 0.25 µg/mL by scavenging DPPH free radicals. SF5 showed significant antioxidant activity in total antioxidant capacity (TAC) and total reducing power (TRP) assays. SF5 and SF9 showed the maximum inhibition of α-amylase enzyme i.e., 97.47% and 89.93%, respectively, at 200 µg/mL concentration. Five compounds were shortlisted to determine their anti-proliferative potential against Hep-2C cells. The study was conducted for 24, 48 and 72 h. SF8 showed significant results, having an IC50 value of 11.9 ± 1.04 µM at 72 h when compared with standard cisplatin (IC50 value of 14.6 ± 1.01 µM). An in vitro nitric oxide (NO) assay was performed to select compounds for in vivo anti-inflammatory activity evaluation. SF13 scavenged the NO level to a maximum of 85% at 50 µM concentration, followed by SF1 and SF2. Based on the NO scavenging assay results, in vivo anti-inflammatory studies were also performed and the results showed significant activity compared to the standard, acetylsalicylic acid (ASA).

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“…Introducing active groups of natural products is an effective and important method for the discovery of new agrochemicals [ 7 , 8 ]. 1,2,3,4-tetrahydroquinoline (THQ), widely existing in natural products [ 9 , 10 ], has been often reported for its favorable bioactivities, such as anticancer [ 11 , 12 ], antibacterial [ 13 , 14 ], antifungal [ 15 , 16 ] activities, and so on. For example, aspernigerin (Fig.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and fungicidal activity of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline

Lei

Zhang

Yan

et al. 2016

Chemistry Central Journal

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BackgroundTake-all of wheat, caused by the soil-borne fungus Gaeumannomyces graminis var. tritici, is one of the most important and widespread root diseases. Given that take-all is still hard to control, it is necessary to develop new effective agrochemicals. Pyrazole derivatives have been often reported for their favorable bioactivities. In order to discover compounds with high fungicidal activity and simple structures, 1,2,3,4-tetrahydroquinoline, a biologically active group of natural products, was introduced to pyrazole structure. A series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were synthesized, and their fungicidal activities were evaluated.ResultsThe bioassay results demonstrated that the title compounds displayed obvious fungicidal activities at a concentration of 50 μg/mL, especially against V. mali, S. sclerotiorum and G. graminis var. tritici. The inhibition rates of compounds 10d, 10e, 10h, 10i and 10j against G. graminis var. tritici were all above 90 %. Even at a lower concentration of 16.7 μg/mL, compounds 10d and 10e exhibited satisfied activities of 100 % and 94.0 %, respectively. It is comparable to that of the positive control pyraclostrobin with 100 % inhibition rate.ConclusionA series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were synthesized and their structures were confirmed by 1H NMR, 13C NMR, IR spectrum and HRMS or elemental analysis. The crystal structure of compound 10g was confirmed by X-ray diffraction. Bioassay results indicated that all title compounds exhibited obvious fungicidal activities. In particular, compounds 10d and 10e showed comparable activities against G. graminis var. tritici with the commercial fungicide pyraclostrobin at the concentration of 16.7 μg/mL.Graphical abstractA series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were designed and synthesized. Bioassay results indicated that all these compounds exhibited obvious fungicidal activities.Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-016-0186-8) contains supplementary material, which is available to authorized users.

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Discovery of 4-Amino and 4-Hydroxy-1-aroylindoles as Potent Tubulin Polymerization Inhibitors

Cited by 66 publications

References 33 publications

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

One-Pot Multicomponent Synthesis and Bioevaluation of Tetrahydroquinoline Derivatives as Potential Antioxidants, α-Amylase Enzyme Inhibitors, Anti-Cancerous and Anti-Inflammatory Agents

Synthesis and fungicidal activity of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline

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