2213-63-0Relevant articles and documents
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Kuhn et al.
, p. 1843 (1968)
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Functionalization of gold nanoparticles with two aminoalcohol-based quinoxaline derivatives for targeting phosphoinositide 3-kinases (PI3Kα)
Araújo, Janine,Menezes, Fabrício G.,Silva, Heloiza F. O.,Vieira, Davi S.,Silva, Sergio R. B.,Bortoluzzi, Adailton J.,Sant'Anna, Celso,Eugenio, Mateus,Neri, Jannyely M.,Gasparotto, Luiz H. S.
, p. 1803 - 1811 (2019)
Quinoxaline derivatives have attracted considerable attention due to their vast range of applications that includes electroluminescence and biomedicine. Concerning the latter, the literature has shown that compounds with a quinoxaline motif bind quite efficiently to phosphatidylinositol-4,5-bisphosphate 3-kinases (PI3Ks), which are enzymes found to be overexpressed in some types of neoplasms. In the present study, gold nanoparticles (AuNPs) were easily functionalized with 2,3-diethanolminoquinoxaline (DEQX) and 2-(2,3-dihydro-[1,4]oxazino[2,3-b]quinoxalin-4-yl)ethanol (OAQX). We made use of glycerol in alkaline media as reducing agent and the quinoxalines served as capping ligands to stabilize the AuNPs. This is the first report on the modification of a nanostructure with quinoxalines. Functionalization confers nanoparticles the required specificity to target only cancer cells, which opens possibilities for phototherapy since the modified AuNPs would concentrate in the tumor tissue as a consequence of PI3Kα overexpression. Molecular dynamics simulations have shown that DEQX and OAQX are potential inhibitors of PI3Kα since they bind to the active site of the enzyme in a way similar to other known inhibitors.
Synthesis, biological evaluation, and molecular docking of new series of antitumor and apoptosis inducers designed as VEGFR-2 inhibitors
Abdallah, Abdallah E.,Abo-Saif, Mariam A.,Al Ward, Maged Mohammed Saleh,Alesawy, Mohamed S.,Eissa, Sally I.,El-Feky, Ola A.,El-Zahabi, Mohamed Ayman,Elkaeed, Eslam B.,Mabrouk, Reda R.,Mehany, Ahmed B. M.
, p. 573 - 591 (2022/01/20)
Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15a, 15b, and 15d showed IC50 from 17.39 to 47.10 μM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15d which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 μM against aforementioned cell lines, respectively. Furthermore, Compound 15d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15d showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively.
Novel molecular targeting anti-tumor aza-steroid derivative based on lipid toxicity and preparation and application thereof
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Paragraph 0178; 0180; 0192; 0205; 0224, (2021/08/19)
The invention provides a novel molecular targeting anti-tumor aza-steroid derivative based on lipid toxicity and a preparation method and application thereof, and belongs to the field of chemical medicines. The derivative is a compound as shown in a formula I, or a salt thereof, or a stereoisomer thereof. The compound is low in toxicity or basically non-toxic to normal cells, has an obvious inhibition effect to tumor cell lines, particularly has good lipid toxicity selectivity to tumor cells such as liver cancer, lung cancer and the like in vivo, and has an obvious inhibition effect; meanwhile, the compound can effectively activate SREBP1 and PPAR gamma, inhibit lipid transport MTTP, cause lipid aggregation in tumor cells and cause lipid toxicity of the tumor cells. The compound can be used for treating liver cancer, lung cancer and the like in a molecular targeting manner, is low in toxicity or even non-toxic, and has a good application prospect.
Triazolo[4,3-a] quinoxaline and [1,2,4]triazolo[4,3- a] quinoxaline-1-thiol-derived DNA intercalators: Design, synthesis, molecular docking, in silico ADMET profiles and anti-proliferative evaluations
El-Adl, Khaled,El-Helby, Abdel-Ghany A.,Sakr, Helmy,Elwan, Alaa
, p. 881 - 897 (2021/01/25)
In view of their DNA intercalation activities as anticancer agents, 17 novel [1,2,4]triazolo[4,3-a]quinoxaline derivatives have been designed, synthesized and evaluated against HepG2, HCT-116 and MCF-7 cells. Molecular docking studies were performed to investigate the binding modes of the proposed compounds with the DNA active site. The data obtained from biological testing highly correlated with those obtained from the molecular modeling studies. MCF-7 was found to be the most sensitive cell line to the influence of the new derivatives. In particular, compound 12d was found to be the most potent derivative of all the tested compounds against the three HepG2, HCT116 and MCF-7 cancer cell lines, with IC50 = 22.08 ± 2.1, 27.13 ± 2.2 and 17.12 ± 1.5 μM, respectively. Although this compound displayed nearly one third of the activity of doxorubicin (IC50 = 7.94 ± 0.6, 8.07 ± 0.8 and 6.75 ± 0.4 μM, respectively), it may be useful as a template for future design, optimization, and investigation to produce more potent anticancer analogs. Compounds 12a, 10c and 10d displayed very good anticancer activities against the three HepG2, HCT116 and MCF-7 cancer cell lines, with IC50 = 31.40 ± 2.8, 28.81 ± 2.4 and 19.72 ± 1.5 μM for 12a, 33.41 ± 2.9, 29.96 ± 2.5 and 24.78 ± 1.9 μM for 10c, and 37.55 ± 3.3, 30.22 ± 2.6 and 25.53 ± 2.0 μM for 10d. The most active derivatives, 10c, 10d, 10h, 12a, 12b and 12d, were evaluated for their DNA binding activities. Compound 12d displayed the highest binding affinity. This compound potently intercalates DNA at a decreased IC50 value (35.33 ± 1.8 μM), which is nearly equipotent to that of doxorubicin (31.27 ± 1.8 μM). Compounds 12a and 10c exhibited good DNA-binding affinities, with IC50 values of 39.35 ± 3.9 and 42.35 ± 3.9 μM, respectively. Finally, compounds 10d, 10h and 12b showed moderate DNA-binding affinities, with IC50 values of 50.35 ± 3.9, 57.08 ± 3.3 and 59.35 ± 3.2 μM, respectively.
