Synthesis of esters derived from 2,3,4,6-tetra-O-acetyl-1-[4-(2-hydroxyethyl)-1H-1,2,3-triazol-1-yl]-β-D-glucopyranose

Pinto, Tiago Dinis; Silva, Marília; Cunha, Sílvia; Oliveira‐Campos, Ana M. F.; Rodrigues, Lígia M.; Hrdina, Radim; Esteves, Ana Paula

doi:10.5155/eurjchem.4.1.64-69.735

Cited by 2 publications

(2 citation statements)

References 32 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The synthetic process for the target compounds was initiated with a trial to prepare the furoxan moiety from allyl ether precursors 3a-d. As depicted in Scheme 1, the phenolic derivatives 2a-h were prepared from alkylidyne malononitrile, through a multi-step reaction, with reasonable yields [42]. Compounds 2a-d were alkylated, using allyl bromide, to obtain the allyloxy derivatives 3a-d [42][43][44][45]. Upon treating compounds 3a-d with sodium nitrite, an electrophilic aromatic substitution reaction took place at the ortho position to an allyloxy group, wherein the carbons were more shielded, thus providing the nitrated derivatives 5a-d, rather than the desired compound 4 [46].…”

Section: Chemistrymentioning

confidence: 99%

“…After 15 min of reflux, another equivalent of sodium hydroxide was added, and the reflux was continued for another 30 min (TLC monitoring). After cooling, the precipitated solid was filtered, washed with ethanol, dried, and recrystallized from acetonitrile to yield the allyloxy derivatives 3a-d [43][44][45].…”

Section: General Procedures For Preparation Of Allyloxy Derivatives (...mentioning

confidence: 99%

See 1 more Smart Citation

Design, Synthesis, and Biological Evaluation of a Novel VEGFR-2 Inhibitor Based on a 1,2,5-Oxadiazole-2-Oxide Scaffold with MAPK Signaling Pathway Inhibition

et al. 2022

View full text Add to dashboard Cite

Over the past few decades, the development of broad-spectrum anticancer agents with anti-angiogenic activity has witnessed considerable progress. In this study, a new series of pyrazolo[3 ,4-d]pyrimidines based on a phenylfuroxan scaffold were designed, synthesized, and evaluated, in terms of their anticancer activities. NCI-60 cell one-dose screening revealed that compounds 12a–c and 14a had the best MGI%, among the tested compounds. The target fluorinated compound 12b, as the most active one, showed better anticancer activity compared to the reference drug sorafenib, with IC50 values of 11.5, 11.6, and 13 µM against the HepG-2, A2780CP, and MDA-MB-231 cell lines, respectively. Furthermore, compound 12b (IC50 = 0.092 µM) had VEGFR-2-inhibitory activity comparable to that of the standard inhibitor sorafenib (IC50 = 0.049 µM). Furthermore, the ability of compound 12b in modulating MAPK signaling pathways was investigated. It was found to decrease the level of total ERK and its phosphorylated form, as well as leading to the down-regulation of metalloproteinase MMP-9 and the over-expression of p21 and p27, thus leading to subG1 cell-cycle arrest and, thus, the induction of apoptosis. Additionally, compound 12b decreased the rate of wound healing in the absence of serum, in comparison to DMSO-treated cells, providing a significant impact on metastasis inhibition. The quantitative RT-PCR results for E-cadherin and N-cadherin showed lower expression of the neuronal N-cadherin and increased expression of epithelial E-cadherin, indicating the ability of 12b to suppress metastasis. Furthermore, 12b-treated HepG2 cells expressed a low level of anti-apoptotic Bcl-2 and over-expressed proapoptotic Bax genes, respectively. Using the DAF-FM DA fluorescence probe, compound 12b produced NO intracellularly as efficiently as the reference drug JS-K. In silico molecular docking studies showed a structural similarity through an overlay of 12b with sorafenib. Interestingly, the drug-likeness properties of compound 12b met the expectations of Pfizer’s rule for the design of new drug candidates. Therefore, this study presents a novel anticancer lead compound that is worthy of further investigation and activity improvement.

show abstract

Section: Chemistrymentioning

confidence: 99%

Section: General Procedures For Preparation Of Allyloxy Derivatives (...mentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of a Novel VEGFR-2 Inhibitor Based on a 1,2,5-Oxadiazole-2-Oxide Scaffold with MAPK Signaling Pathway Inhibition

et al. 2022

View full text Add to dashboard Cite

show abstract

Design and synthesis of pyrazolo[3,4- d ]pyrimidines: Nitric oxide releasing compounds targeting hepatocellular carcinoma

Elshaier

Shaaban

Hamid

et al. 2017

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

Synthesis of esters derived from 2,3,4,6-tetra-O-acetyl-1-[4-(2-hydroxyethyl)-1H-1,2,3-triazol-1-yl]-β-D-glucopyranose

Cited by 2 publications

References 32 publications

Design, Synthesis, and Biological Evaluation of a Novel VEGFR-2 Inhibitor Based on a 1,2,5-Oxadiazole-2-Oxide Scaffold with MAPK Signaling Pathway Inhibition

Design, Synthesis, and Biological Evaluation of a Novel VEGFR-2 Inhibitor Based on a 1,2,5-Oxadiazole-2-Oxide Scaffold with MAPK Signaling Pathway Inhibition

Design and synthesis of pyrazolo[3,4- d ]pyrimidines: Nitric oxide releasing compounds targeting hepatocellular carcinoma

Contact Info

Product

Resources

About