7712-28-9Relevant articles and documents
Design, synthesis, antiproliferative evaluation, and molecular docking study of new quinoxaline derivatives as apoptotic inducers and EGFR inhibitors
Fayed, Eman A.,Ammar, Yousry A.,Saleh, Marwa A.,Bayoumi, Ashraf H.,Belal, Amany,Mehany, Ahmed B.M.,Ragab, Ahmed
, (2021)
A new series of quinoxaline derivatives synthesized and pharmacologically evaluated against (HepG-2, HCT-116, and MCF-7) cell lines. Seven compounds were found to possess the highest activities against the examined cell lines with IC50 values ranging from (7.57 to 28.44 μM). To further analyze its apoptotic potential in MCF-7 cells, the most active 3a, 3b, 6, 7b, 7c, 7d, and 7f members have been selected. Interestingly, it found that the Bcl-2 level decreased by 1.95–3.99 folds, and the BAX level increased by 7.2-10.6 folds relative to the control. They also increased the active Caspase-3 level by 5.77-10.69 folds compared to untreated cells. WI38 cells were treated with these compounds to estimate the cytotoxicity level of those compounds in non-tumorigenic cells, and they displayed higher IC50 values (142.21-335.03μM), suggesting may less toxic effect on the normal ones. Further studies on the mechanism of the most promising compounds 3a, 6, 7b and 7d, revealed that it increases apoptotic cells and induced cell cycle arrest at pre-G1 and G2/M phases. Besides, both wild EGFRWT and mutant EGFRL858R-TK inhibitory activity for these derivatives showed that these derivatives had IC50 values ranging from 0.075-1.547 μM versus wild EGFRWT and 63.70-87.34 nM versus the mutant type. Erlotinib was used as a standard reference with IC50 values of 0.0656 μM and 59.56 nM versus both types. Finally, the molecular docking study of most potent quinoxaline derivatives exhibited a good binding inside the active site of EGFR (1M17), with binding energy ranged between (-15.86 to -16.97) compared to Erlotinib (-17.84) kcal/mol. Also, by applying Lipinski's parameters, it was found that these derivatives showed no violations and indicated promiscuity to formulate orally.
Design, synthesis and biological evaluation of quinoxaline compounds as anti-HIV agents targeting reverse transcriptase enzyme
Estrin, Darío,Fabian, Lucas,Gómez, Natalia,Moglioni, Albertina,Salvatori, Melina,Taverna Porro, Marisa,Turk, Gabriela
, (2019/12/30)
Infection by human immunodeficiency virus still represents a continuous serious concern and a global threat to human health. Due to appearance of multi-resistant virus strains and the serious adverse side effects of the antiretroviral therapy administered, there is an urgent need for the development of new treatment agents, more active, less toxic and with increased tolerability to mutations. Quinoxaline derivatives are an emergent class of heterocyclic compounds with a wide spectrum of biological activities and therapeutic applications. These types of compounds have also shown high potency in the inhibition of HIV reverse transcriptase and HIV replication in cell culture. For these reasons we propose, in this work, the design, synthesis and biological evaluation of quinoxaline derivatives targeting HIV reverse transcriptase enzyme. For this, we first carried out a structure-based development of target-specific compound virtual chemical library of quinoxaline derivatives. The rational construction of the virtual chemical library was based on previously assigned pharmacophore features. This library was processed by a virtual screening protocol employing molecular docking and 3D-QSAR. Twenty-five quinoxaline compounds were selected for synthesis in the basis of their docking and 3D-QSAR scores and chemical synthetic simplicity. They were evaluated as inhibitors of the recombinant wild-type reverse transcriptase enzyme. Finally, the anti-HIV activity and cytotoxicity of the synthesized quinoxaline compounds with highest reverse transcriptase inhibitory capabilities was evaluated. This simple screening strategy led to the discovery of two selective and potent quinoxaline reverse transcriptase inhibitors with high selectivity index.
Quinoxaline derivatives with MMP (matrix metalloproteinase) inhibitory activity as well as preparation method and application thereof
-
Paragraph 0100; 0101; 0102, (2019/01/08)
The invention discloses quinoxaline derivatives with MMP (matrix metalloproteinase) inhibitory activity as well as a preparation method and application thereof. In the invention, a series of quinoxaline derivatives with specific MMP-9 and/or MMP-13 inhibitory activity are synthesized, and the type of compounds can serve as a specific MMP-9 and/or MMP-13 inhibitor, so that a clinical drug with higher therapeutic index is formed, and the problems in the prior art that drugs for treating osteoarthritis, osteoarthritis, osteoporosis and periodontitis are fewer in type and are not exact in curativeeffect, etc. are solved.
