Glutarimide: a carrier transporting drug through cell membranes

Michalska, Danuta; Morzyk, Barbara; Bieńko, Dariusz C.; Wojciechowski, W.

doi:10.1054/mehy.1999.0879

Cited by 14 publications

(10 citation statements)

References 18 publications

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“…Research into a small class of bipartite compounds of the glutarimide‐polyketide estate gained considerable momentum once the cell‐migration inhibition properties of migrastatin ( 3 ) had been recognized 1–4. Since this mode of action might ultimately translate into medication to prevent cancer metastasis, clinically viable cell migration inhibitors could form a second line of defense against cancer, complementing conventional chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Total Syntheses and Biological Reassessment of Lactimidomycin, Isomigrastatin and Congener Glutarimide Antibiotics

Micoine

Persich

Llaveria

et al. 2013

Chemistry A European J

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Lactimidomycin (1) was described in the literature as an exquisitely potent cell migration inhibitor. Encouraged by this claim, we developed a concise and scalable synthesis of this bipartite glutarimide-macrolide antibiotic, which relies on the power of ring-closing alkyne metathesis (RCAM) for the formation of the unusually strained 12-membered head group. Subsequent deliberate digression from the successful path to 1 also brought the sister compound isomigrastatin (2) as well as a series of non-natural analogues of these macrolides into reach. A careful biological re-evaluation of this compound collection showed 1 and progeny to be potently cytotoxic against a panel of cancer cell lines, even after one day of compound exposure; therefore any potentially specific effects on tumor cell migration were indistinguishable from the acute effect of cell death. No significant cell migration inhibition was observed at sub-toxic doses. Although these findings cannot be reconciled with some reports in the literature, they are in accord with the notion that lactimidomycin is primarily a ribosome-binder able to effectively halt protein biosynthesis at the translation stage.

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Section: Introductionmentioning

confidence: 99%

Total Syntheses and Biological Reassessment of Lactimidomycin, Isomigrastatin and Congener Glutarimide Antibiotics

Micoine

Persich

Llaveria

et al. 2013

Chemistry A European J

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“…The structural features and physiochemical properties of the glutarimide moiety is remarkably similar to the uracil derivatives. Therefore, it interacts with specific receptors involved in transport of uracil and thymine nucleosides across biological membranes [28,29]. Being a constituent of a large number of other important compounds, the glutarimide moeity possesses a broad spectrum of pharmacological and anticancer properties [2,30,31].…”

Section: Discussionmentioning

confidence: 99%

Chemical modification of L-glutamine to alpha-amino glutarimide on autoclaving facilitates Agrobacterium infection of host and non-host plants: A new use of a known compound

et al. 2011

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BackgroundAccidental autoclaving of L-glutamine was found to facilitate the Agrobacterium infection of a non host plant like tea in an earlier study. In the present communication, we elucidate the structural changes in L-glutamine due to autoclaving and also confirm the role of heat transformed L-glutamine in Agrobacterium mediated genetic transformation of host/non host plants.ResultsWhen autoclaved at 121°C and 15 psi for 20 or 40 min, L-glutamine was structurally modified into 5-oxo proline and 3-amino glutarimide (α-amino glutarimide), respectively. Of the two autoclaved products, only α-amino glutarimide facilitated Agrobacterium infection of a number of resistant to susceptible plants. However, the compound did not have any vir gene inducing property.ConclusionsWe report a one pot autoclave process for the synthesis of 5-oxo proline and α-amino glutarimide from L-glutamine. Xenobiotic detoxifying property of α-amino glutarimide is also proposed.

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“…Estudos recentes têm demonstrado que o grupo glutarimídico substituído em posição α ou β no anel, age como uma molécula carreadora, transportando biologicamente os substituintes ativos através das membranas celulares 91 .…”

Section: Aspectos Biológicosunclassified

Aspectos químicos e potencial terapêutico de imidas cíclicas: uma revisão da literatura

Filho¹,

Campos²,

Corrêa³

et al. 2003

Quím. Nova

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Recebido em 15/4/02; aceito em 19/7/02 CHEMICAL ASPECTS AND THERAPEUTIC POTENTIAL OF CYCLIC IMIDES: A REVIEW. Cyclic imides consists of an important family of organic compounds with therapeutic potential. In this review, emphasis will be given to the chemical and biological aspects of several sub-classes of this family, incluing maleimides, succinimides, glutarimides, naphtalimides, etc. Additionally, will be focused the contribution of our research group in this field.Keywords: cyclic imides; synthesis; biological activities. INTRODUÇÃOA necessidade do desenvolvimento de novos fármacos, que sejam efetivos contra algumas patologias ainda sem tratamento adequado, e que possam substituir os existentes, porém a custos menores e dotados de menores efeitos adversos, tem impulsionado a comunidade científica a novas e incessantes pesquisas nesta área. A síntese orgânica tem contribuído significativamente neste aspecto, sendo responsável por cerca de 75% dos fármacos existentes no mercado farmacêutico 1,2 . Cabe ressaltar, porém, que muitos destes fármacos são oriundos de protótipos advindos de produtos naturais, especialmente de plantas, que têm, ao longo dos anos, possibilitado a descoberta de inúmeras moléculas bio-ativas 3-6 .Muitas classes de compostos orgânicos têm demonstrado promissores efeitos biológicos e a literatura científica relata um crescimento significativo de novas moléculas com potência similar ou superior àquela de um fármaco, sendo que muitos deles encontram-se em estudos pré-clínicos e clínicos avançados e pormenorizados. Entre estas substâncias, pode-se inserir as imidas cíclicas, alvo desta revisão.As imidas cíclicas são compostos que contém o grupo -CO-N(R)-CO-, sendo R um átomo de hidrogênio, grupo alquila ou grupo arila. Tais compostos podem ser divididos em sub-classes, incluindo as maleimidas, succinimidas, glutarimidas, ftalimidas, naftalimidas, etc., e seus respectivos derivados. Em 1970, Hargreaves e colaboradores 7 publicaram uma revisão abordando vários aspectos químicos, industriais e biológicos das imidas cíclicas. Nos últimos anos, esta classe de compostos tem ressurgido e atraído a atenção da comunidade científica, devido, principalmente, às suas potencialidades terapêuticas. Como exemplo, podemos citar o caso da talidomida (1) que apesar dos significativos efeitos adversos do passado, ocasionando praticamente 100% de teratogenicidade, mesmo em doses clí-nicas modestas, sendo sua indicação específica para uso na gravidez 8 , os recentes estudos têm evidenciado um possível uso desta substância para o tratamento de várias patologias incluindo o câncer 9-11 .Os departamentos de Química e Farmacologia da UFSC e o Núcleo de Investigações Químico-Farmacêuticas da UNIVALI iniciaram os estudos com esta classe de compostos a partir da descoberta do alcalóide natural filantimida (2), isolado das partes aéreas do Phyllanthus sellowianus 12 . Este composto, derivado da glutarimida, apresentou moderado efeito antimicrobiano 13 , antiespasmódico 14 e analgésico 15,16 , sendo então usado como mode...

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Glutarimide: a carrier transporting drug through cell membranes

Cited by 14 publications

References 18 publications

Total Syntheses and Biological Reassessment of Lactimidomycin, Isomigrastatin and Congener Glutarimide Antibiotics

Total Syntheses and Biological Reassessment of Lactimidomycin, Isomigrastatin and Congener Glutarimide Antibiotics

Chemical modification of L-glutamine to alpha-amino glutarimide on autoclaving facilitates Agrobacterium infection of host and non-host plants: A new use of a known compound

Aspectos químicos e potencial terapêutico de imidas cíclicas: uma revisão da literatura

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