The Impact of [C16Pyr][Amp] on the Aggressiveness in Breast and Prostate Cancer Cell Lines

Breast (BrCa) and prostate (PCa) cancers are the most common malignancies in women and men, respectively. The available therapeutic options for these tumors are still not curative and have severe side effects. Therefore, there is an urgent need for more effective antineoplastic agents. Herein, BrCa, PCa, and benign cell lines were treated with two ionic liquids and two quinoxalines and functional experiments were performed—namely cell viability, apoptosis, cytotoxicity, and colony formation assays. At the molecular level, an array of gene expressions encompassing several molecular pathways were used to explore the impact of treatment on gene expression. Although both quinoxalines and the ionic liquid [C2OHMIM][Amp] did not show any effect on the BrCa and PCa cell lines, [C16Pyr][Amp] significantly decreased cell viability and colony formation ability, while it increased the apoptosis levels of all cell lines. Importantly, [C16Pyr][Amp] was found to be more selective for cancer cells and less toxic than cisplatin. At the molecular level, this ionic liquid was also associated with reduced expression levels of CPT2, LDHA, MCM2, and SKP2, in both BrCa and PCa cell lines. Hence, [C16Pyr][Amp] was shown to be a promising anticancer therapeutic agent for BrCa and PCa cell lines.     

Development of new dyeing photoinitiators based on 6H-indolo[2,3-b]quinoxaline skeleton

The series of new dyes, which structures are based on 6H-indolo[2,3-b]quinoxaline skeleton that possess characteristic electronic absorption band at a boundary of UV and visible light were tested as potential light absorbing chromophores for photoinitiated polymerization.The studied dyes can be classified into two different groups. The first is the group, so called ‘the branched dyes’, which structures possess the part of molecule that can rotate without restraints and are characterized by low photoinitiation ability. The second, planar and rigid group of molecules provides another chromophores, which possess quite different properties in comparison to that observed for the branched dyes. Their photoinitiation ability is comparable to that observed for many commercially available photoinitiating systems.The location of electronic absorption spectra at a boundary of UV and visible light makes the tested dyes the good candidates for the photoinitiating system applied in dental restorative materials. Their high molar absorption coefficient allows to decrease the dyes concentration in dental formulation in comparison to commonly used camphorquinone.     

TBHP-Mediated Intermolecular Radical Coupling and Intramolecular Cyclization Cascade: Access to Furo[2,3-b]quinoxalines and Their Photophysical Study

A cascade one-pot strategy to construct 31 examples of furo-fused quinoxalines in up to 88% yields has been devised from readily accessible β-ketothioamides and quinoxalin-2-ones in open flask at room temperature under TBHP mediated conditions. Mechanistic studies revealed that the overall reactivity relies on the seamless integration of intermolecular radical coupling and intramolecular cyclization via desulfhydration of C=S bond cleavage. Generation of H₂S as the only by-product makes this process highly attractive. Furthermore, the photophysical behavior of the furo-fused quinoxalines has also been studied.     

Structure–Activity Relationships of Quinoxaline‐Based 5‐HT3A and 5‐HT3AB Receptor‐Selective Ligands

Until recently, discriminating between homomeric 5‐HT₃A and heteromeric 5‐HT₃AB receptors was only possible with ligands that bind in the receptor pore. This study describes the first series of ligands that can discriminate between these receptor types at the level of the orthosteric binding site. During a recent fragment screen, 2‐chloro‐3‐(4‐methylpiperazin‐1‐yl)quinoxaline (VUF10166) was identified as a ligand that displays an 83‐fold difference in [³H]granisetron binding affinity between 5‐HT₃A and 5‐HT₃AB receptors. Fragment hit exploration, initiated from VUF10166 and 3‐(4‐methylpiperazin‐1‐yl)quinoxalin‐2‐ol, resulted in a series of compounds with higher affinity at either 5‐HT₃A or 5‐HT₃AB receptors. These ligands reveal that a single atom is sufficient to change the selectivity profile of a compound. At the extremes of the new compounds were 2‐amino‐3‐(4‐methylpiperazin‐1‐yl)quinoxaline, which showed 11‐fold selectivity for the 5‐HT₃A receptor, and 2‐(4‐methylpiperazin‐1‐yl)quinoxaline, which showed an 8.3‐fold selectivity for the 5‐HT₃AB receptor. These compounds represent novel molecular tools for studying 5‐HT₃ receptor subtypes and could help elucidate their physiological roles.     

超高效液相色谱-四极杆/静电场轨道阱高分辨率质谱法测定鸡肉中8种喹噁啉类药物及其代谢产物

目的 建立超高效液相色谱串联四极杆/静电场轨道离子阱高分辨率质谱法同步测定鸡肉中8喹噁种喹啉类药物及其代谢物的分析方法.方法 鸡肉样品分别经过1％甲酸乙腈提取5种喹噁啉类原药和1 mol/L盐酸溶液提取3种代谢物,超声、振荡处理及高速离心后,分别用多重基质吸附填料和Oasis HLB固相萃取柱净化并收集,氮气吹干,用0...     

新型喹噁啉类药物在水产养殖中的有效性及安全性研究进展

喹噁啉类药物是一类人工合成的具有抗菌、促进生长作用的动物专用药, 曾被广泛应用于畜禽和水产养殖业。本类早期品种喹乙醇与卡巴氧被证明有较强的毒副作用, 已被不同程度地限制或禁止使用。近年来研制成功的新型喹噁啉类药物降低了毒性, 保留了抗菌及促生长活性, 已在畜禽养殖中广泛使用。本文对新型喹噁啉类药物的种类、有效性及安全性、代谢动力学及残留消除规律、代谢途径及标识残留物进行了综述, 为该类药物在水产养殖生产中的安全合理应用提供参考。     

Synthetic strategies for thiazoloquinoxalines and their applications

The current review article represents a survey of the literature covering the synthetic strategies leading to thiazoloquinoxalines for the first time. The review is divided into four parts discussing four groups of thiazoloquinoxalines classified based on the type of fusion between the thiazole and quinoxaline nuclei.     

Natural vs. Synthetic Phosphate as Efficient Heterogeneous Compounds for Synthesis of Quinoxalines

Natural phosphate (NP) and synthetic fluorapatite phosphate (SFAP) were proposed as stable, inexpensive, readily available and recyclable catalysts for the condensation of 1,2-diamines with 1,2-dicarbonyls in methanol to afford quinoxaline at room temperature. NP provided as high as 92–99% yield for quinoxalines in short reaction times (i.e., 1–45 min), while SFAP created quinoxalines with 87–97% yield in 60–120 min. From the chemical analyses, X-ray fluoresecency, X-ray diffraction, energy dispersive X-ray and Fourier-transform infrared spectroscopy methods, two main phases (CaO, P₂O₅) appeared in NP together with other low content phases (SiO₂, Fe₂O₃). Compared to other phases, apatite (CaO and P₂O₅ as Ca10(PO₄)₆) played a major role in the catalytic activity of NP. SFAP with similar Ca/P atomic ratio showed a relatively lower catalytic activity than NP for the condensation of 1,2-diamine with 1,2-dicarbonyl in methanol at ambient temperature. To investigate the recyclability of catalysts, the surface properties of NP and 6-recycled NP were investigated using scanning electron microscopy, energy dispersive X-ray and Brunauer–Emmett–Teller and Barrett–Joyner–Halenda methods. Some differences were observed in NP and 6-recycled NP’s particle size, surface area, the volume and size of pores, and the content of elements; nevertheless, the use–reuse process did not noticeably change the catalytic property of NP.     

室温下氨基磺酸催化合成喹(噁)啉衍生物

用廉价、无毒、易得的氨基磺酸作为催化剂,以二氯甲烷为溶剂,用芳香、杂环及脂肪1,2-二酮分别与1,2-二胺在室温下进行缩合反应得到喹噁啉衍生物。考察了溶剂、催化剂用量、反应时间对产物收率的影响,优化的工艺条件为:n(二酮)∶n(二胺)∶n(氨基磺酸)=1∶1∶0.15,反应温度25℃,反应时间6 h,产物最终收率均超过75%。该反应放大200倍后,即在1 L溶剂中,用1 mol的反应物反应时,在优化的工艺条件下产率仍然可以达到70%。氨基磺酸可以循环使用5次而产率保持稳定。     

An efficient synthesis of quinoxalinone derivatives as potent inhibitors of aldose reductase

A novel and facile synthesis of quinoxalinone derivatives was developed in which a wide range of 3-chloroquinoxalin-2(1H)-ones as key intermediates can be generated chemo- and regioselectively in good yields from corresponding quinoxaline-2,3(1H,4H)-diones. This new protocol is arguably superior, as it allows the design and preparation of a variety of bioactive quinoxaline-based compounds, which are particularly effective in the treatment of diabetes and its complications. Through this procedure, a new class of quinoxalinone-based aldose reductase inhibitors were synthesized successfully. Most of the inhibitors, with an N1-acetic acid head group and a substituted C3-phenoxy side chain, proved to be potent and selective. Their IC(50) values ranged from 11.4 to 74.8 nM. Among them, 2-(3-(4-bromophenoxy)-7-fluoro-2-oxoquinoxalin-1(2H)-yl)acetic acid and 2-(6-bromo-3-(4-bromophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid were the most active. Structure-activity relationship and molecular docking studies highlighted the importance of the ether spacer in the C3-phenoxy side chains, and provided clear guidance on the contribution of substitutions both at the core structure and the side chain to activity.