Structural feature evolution – from fluids to the solid phase – and crystal morphology study of LASSBio 1601: a cyclohexyl-N-acylhydrazone derivative

Costa, Fanny N.; Silva, Tiago Fiorini da; Silva, Eduardo Miguez B.; Barroso, R.C.; Braz, Delson; Barreiro, Eliezer J.; Lima, Lı́dia Moreira; Punzo, Francesco; Ferreira, Fábio Furlan

doi:10.1039/c5ra02696b

Cited by 7 publications

(4 citation statements)

References 72 publications

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“…The only exception was the N ′-cyclopentanecarbohydrazides 6h and 7h that in carbon and proton NMR spectra exhibited two set of resonance signals. Following the findings of Ferreira and co-workers [ 50 ], we assumed that the observed doubled signals refer to the presence of both the cis / E and trans / E amide conformers. For example, in the 13 C NMR spectrum of 6h , the signals at 172.5 ppm and 177.8 ppm referred to the carbon atoms of the amide C=O group of the cis and trans conformers, while the 1 H NMR spectrum of 6h revealed the presence of two separate singlets at 11.67 ppm and 11.42 ppm attributable to the protons of the amide C(O)–NH group.…”

Section: Resultsmentioning

confidence: 77%

“…Literature reports for N -acyl- and N -aroylhydrazones derived from aryl- and heteroaryl aldehydes indicate that these compounds may exist both in DMSO- d 6 solution [ 39 , 40 , 41 , 42 ] and solid phase [ 43 , 44 , 45 , 46 ] in the form of E -geometrical isomers. Other studies revealed the presence of the mixtures of two forms: cis and trans amide conformers of N -acyl- [ 39 , 40 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ] and N -aroylhydrazones [ 52 , 53 ] in solution.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis, Structure, Chemical Stability, and In Vitro Cytotoxic Properties of Novel Quinoline-3-Carbaldehyde Hydrazones Bearing a 1,2,4-Triazole or Benzotriazole Moiety

et al. 2018

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A small library of novel quinoline-3-carbaldehyde hydrazones (Series 1), acylhydrazones (Series 2), and arylsulfonylhydrazones (Series 3) bearing either a 1,2,4-triazole or benzotriazole ring at position 2 was prepared, characterized by elemental analyses and IR, NMR, and MS spectra, and then subjected to in vitro cytotoxicity studies on three human tumor cell lines: DAN-G, LCLC-103H, and SISO. In general, compounds 4, 6, and 8 substituted with a 1,2,4-triazole ring proved to be inactive, whereas the benzotriazole-containing quinolines 5, 7, and 9 elicited pronounced cancer cell growth inhibitory effects with IC50 values in the range of 1.23–7.39 µM. The most potent 2-(1H-benzotriazol-1-yl)-3-[2-(pyridin-2-yl)hydrazonomethyl]quinoline (5e) showed a cytostatic effect on the cancer cell lines, whereas N′-[(2-(1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-benzohydrazide (7a) and N′-[(2-1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-naphthalene-2-sulfonohydrazide (9h) exhibited selective activity against the pancreas cancer DAN-G and cervical cancer SISO cell lines. Based on the determined IC50 values, the compound 5e seems to be leading compound for further development as anticancer agent.

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Section: Resultsmentioning

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Synthesis, Structure, Chemical Stability, and In Vitro Cytotoxic Properties of Novel Quinoline-3-Carbaldehyde Hydrazones Bearing a 1,2,4-Triazole or Benzotriazole Moiety

et al. 2018

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“…Atherosclerosis can lead to different cardiac diseases responsible for more than 17.3 million deaths annually worldwide [ 2 ]. Nowadays, CIP is commercially available for oral formulations as tablets and capsules (100 mg) [ 3 ], and patients report several side effects such as headaches, nausea, and diarrhea [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Ciprofibrate-Loaded Nanoparticles Prepared by Nanoprecipitation: Synthesis, Characterization, and Drug Release

et al. 2021

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Ciprofibrate (CIP) is a highly lipophilic and poorly water-soluble drug, typically used for dyslipidemia treatment. Although it is already commercialized in capsules, no previous studies report its solid-state structure; thus, information about the correlation with its physicochemical properties lacking. In parallel, recent studies have led to the improvement of drug administration, including encapsulation in polymeric nanoparticles (NPs). Here, we present CIP’s crystal structure determined by PDRX data. We also propose an encapsulation method for CIP in micelles produced from Pluronic P123/F127 and PEO-b-PCL, aiming to improve its solubility, hydrophilicity, and delivery. We determined the NPs’ physicochemical properties by DLS, SLS, ELS, and SAXS and the loaded drug amount by UV-Vis spectroscopy. Micelles showed sizes around 10–20 nm for Pluronic and 35–45 nm for the PEO-b-PCL NPs with slightly negative surface charge and successful CIP loading, especially for the latter; a substantial reduction in ζ-potential may be evidenced. For Pluronic nanoparticles, we scanned different conditions for the CIP loading, and its encapsulation efficiency was reduced while the drug content increased in the nanoprecipitation protocol. We also performed in vitro release experiments; results demonstrate that probe release is driven by Fickian diffusion for the Pluronic NPs and a zero-order model for PEO-b-PCL NPs.

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“…Reação geral de formação de uma hidrazona Ao longo dos anos tem sido descrito na literatura, para a classe de compostos orgânicos em questão, um expressivo número de atividades biológicas, tais como: atividade antiviral, anticonvulsivante, antituberculose, antifúngica, antibacteriana, antioxidante, anti-inflamatória, antitumoral, antidepressiva, dentre muitas outras. 4, [13][14][15][16][17] Neste contexto, esta revisão sistemática foi realizada com o objetivo de descrever as atividades biológicas que estão sendo avaliadas e descritas para hidrazonas obtidas sinteticamente nos últimos anos, no período entre 2006 e 2016, e assim avaliar se compostos contendo esse grupo funcional podem ser considerados promissores candidatos a protótipos de novos fármacos.…”

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Biological Potential of Synthetic Hydrazones in the Last Decade: A Systematic Review

Guimarães¹,

Rolim²,

Gonsalves³

et al. 2017

Rev. Virtual Quim.

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Abstract:Hydrazones are a class of organic compounds with the general structure -C=N-NH-, resulting from the condensation of carbonylated substances with amines. The synthesis of this functional group generally occurs by the condensation of hydrazines or hydrazides with aldehydes and ketones. In recent years, the functional group hydrazone has been gaining prominence in medicinal chemistry, due mainly to its wide spectrum of applications and chemical and biological properties, as well as its structural versatility. Thus, this systematic review is aimed to investigate the biological potential of hydrazones obtained synthetically in the last decade.Among the papers included in this study, over 80% of them exhibit promising results for the evaluation activity, and less than 15% of these had unimpressive results. In addition, the relationship and importance of the coordination properties of the hydrazonic derivatives for the evaluated activities became apparent. Moreover, synthetic hydrazones are promising organic substances for the research and development of new chemical prototypes for the discovery of new drugs.Keywords: Hydrazones; Synthesis; Biological activity; Metallic complexes; Coordination. ResumoHidrazonas são uma classe de compostos orgânicos com estrutura geral -C=N-NH-, resultantes da condensação de substâncias carboniladas com aminas. A obtenção deste grupo funcional geralmente ocorre pela condensação de hidrazinas ou hidrazidas com aldeídos e cetonas. Nos últimos anos, o grupo funcional hidrazona vem ganhando destaque na química medicinal, devido principalmente a seu amplo espectro de aplicações e propriedades químicas e biológicas, assim como pela sua versatilidade estrutural. Deste modo, esta revisão sistemática teve como objetivo a investigação do potencial biológico de hidrazonas obtidas sinteticamente na última década. Entre os artigos científicos incluídos neste trabalho, mais de 80% deles apresentaram resultados promissores para a atividade avaliada, e menos de 15% destes exibiram resultados inexpressivos. Em adição, tornou-se perceptível a relação e a importância das propriedades de coordenação dos derivados hidrazônicos para as atividades avaliadas. E ainda, podemos afirmar que as hidrazonas sintéticas são substâncias orgânicas promissoras para a pesquisa e desenvolvimento de novos protótipos químicos visando a descoberta de novos fármacos.

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Structural feature evolution – from fluids to the solid phase – and crystal morphology study of LASSBio 1601: a cyclohexyl-N-acylhydrazone derivative

Cited by 7 publications

References 72 publications

Synthesis, Structure, Chemical Stability, and In Vitro Cytotoxic Properties of Novel Quinoline-3-Carbaldehyde Hydrazones Bearing a 1,2,4-Triazole or Benzotriazole Moiety

Synthesis, Structure, Chemical Stability, and In Vitro Cytotoxic Properties of Novel Quinoline-3-Carbaldehyde Hydrazones Bearing a 1,2,4-Triazole or Benzotriazole Moiety

Ciprofibrate-Loaded Nanoparticles Prepared by Nanoprecipitation: Synthesis, Characterization, and Drug Release

Biological Potential of Synthetic Hydrazones in the Last Decade: A Systematic Review

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