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.
One-pot synthesis of novel substituted quinoxaline piperazine derivatives and their antimicrobial activities
Abdel-Hafez, Shams H.,Fahmy, Heba Mohamed,Hessien, Mahmoud M.,Narasimha Reddy, Y.,Reddy G, Nagaraja,Reddy Mardi, Radhakrishna,Reddy T, Sreenivasulu,Seku, Kondaiah,Shalan, Ahmed Esmail
, (2022/01/06)
The present investigation reports the preparation of 1-(4-(tolyl quinoxaline-2-yl) piperazine-1-yl) derivatives catalyzed via polymer supported reagents. We have developed novel quinoxaline piperazine derivatives from 2,3-dichloroquinoxaline, wherein one chloro group is substituted with an aryl group, and the other is substituted by alkyl and aryl piperazine derivatives, through aromatic nucleophilic substitution reaction, and Suzuki coupling reactions to substituted quinoxaline-piperazine derivatives (5a-5g) compounds. The synthesized compounds were identified using FTIR, 1H NMR, 13C NMR and LC-MS. The synthesized compounds were examined for their antimicrobial activity. The results indicated that 5d, 5f and 5 g compounds have exhibited well to moderate antibacterial activity with the zone of inhibition of 18, 22 and 21 mm for Escherichia coli (40 μg/mL), and 17, 19 and 17 mm for Staphylococcus aureus (40 μg/mL). Besides, 5f compound showed respectable results to moderate antifungal activity with the zone of inhibition of 21 mm for Aspergillus niger (40 μg/mL) and 19 mm for Candida albicans (40 μg/mL). The established synthetic route is beneficial to develop various key intermediates as well as active pharmaceutical ingredients for pharmaceutical applications.
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.
Design, synthesis, and molecular docking studies of new [1,2,4]triazolo[4,3-a]quinoxaline derivatives as potential A2B receptor antagonists
Ezzat, Hany G.,Bayoumi, Ashraf H.,Sherbiny, Farag F.,El-Morsy, Ahmed M.,Ghiaty, Adel,Alswah, Mohamed,Abulkhair, Hamada S.
, p. 291 - 306 (2020/03/24)
Abstract: Many shreds of evidence have recently correlated A2B receptor antagonism with anticancer activity. Hence, the search for an efficient A2B antagonist may help in the development of a new chemotherapeutic agent. In this article, 23 new derivatives of [1,2,4]triazolo[4,3-a]quinoxaline were designed and synthesized and its structures were confirmed by different spectral data and elemental analyses. The results of cytotoxic evaluation of these compounds showed six promising active derivatives with IC50 values ranging from 1.9 to 6.4?μM on MDA-MB 231 cell line. Additionally, molecular docking for all synthesized compounds was performed to predict their binding affinity toward the homology model of A2B receptor as a proposed mode of their cytotoxic activity. Results of molecular docking were strongly correlated with those of the cytotoxic study. Finally, structure activity relationship analyses of the new compounds were explored. Graphic abstract: [Figure not available: see fulltext.]
