38267-96-8Relevant articles and documents
UiO-66-NH2as an effective solid support for quinazoline derivatives for antibacterial agents against Gram-negative bacteria
Al Blooshi, Afra G.,Al Neyadi, Shaikha S.,Alnaqbi, Mohamed. A.,Nguyen, Ha L.
, p. 20386 - 20395 (2021/12/02)
Nanomaterials have been widely used as a class of antibacterial drugs. However, the bottlenecks of this class of materials are their significant aggregation and accumulation, as well as toxicity resulting from excessive metal leaching. Metal-organic frameworks (MOFs) have inspired researchers owing to their distinct characteristics of robust architecture and tunable pore structures, which may help overcome the above challenges. We, herein, synthesize UiO-66-NH2 and use it as a solid support for loading quinazoline derivatives that are specifically designed and active against Gram-negative bacteria. The quinazoline derivatives were adsorbed on UiO-66-NH2 nanoparticles to form new UiO-66-NH2-quinazoline formulations which have a large inhibitory zone against Gram-negative bacteria, compared to that of free quinazoline compounds. This work has the potential for increasing antibacterial activity while also broadening the antibacterial range, and thus opens a pathway for new medical applications using MOFs. This journal is
Discovery of quinazoline derivatives as a novel class of potent and in vivo efficacious LSD1 inhibitors by drug repurposing
Li, Zhonghua,Qin, Tingting,Li, Zhongrui,Zhao, Xuan,Zhang, Xinhui,Zhao, Taoqian,Yang, Nian,Miao, Jinxin,Ma, Jinlian,Zhang, Zhenqiang
, (2021/08/19)
Histone lysine-specific demethylase 1 (LSD1) is an important epigenetic modulator, and is implicated in malignant transformation and tumor pathogenesis in different ways. Therefore, the inhibition of LSD1 provides an attractive therapeutic target for cancer therapy. Based on drug repurposing strategy, we screened our in-house chemical library toward LSD1, and found that the EGFR inhibitor erlotinib, an FDA-approved drug for lung cancer, possessed low potency against LSD1 (IC50 = 35.80 μM). Herein, we report our further medicinal chemistry effort to obtain a highly water-soluble erlotinib analog 5k (>100 mg/mL) with significantly enhanced inhibitory activity against LSD1 (IC50 = 0.69 μM) as well as higher specificity. In MGC-803 cells, 5k suppressed the demethylation of LSD1, indicating its cellular activity against the enzyme. In addition, 5k had a remarkable capacity to inhibit colony formation, suppress migration and induce apoptosis of MGC803 cells. Furthermore, in MGC-803 xenograft mouse model, 5k treatment resulted in significant reduction in tumor size by 81.6% and 96.1% at dosages of 40 and 80 mg/kg/d, respectively. Our findings indicate that erlotinib-based analogs provide a novel structural set of LSD1 inhibitors with potential for further investigation, and may serve as novel candidates for the treatment of LSD1-overexpressing cancers.
Discovery of novel quinazoline derivatives as potent PI3Kδ inhibitors with high selectivity
Teng, Yu,Li, Xinyu,Ren, Shengnan,Cheng, Yu,Xi, Kun,Shen, Hongtao,Ma, Wenzhuo,Luo, Guoshun,Xiang, Hua
, (2020/10/02)
Inhibition of PI3Kδ has been proved to be an efficacious strategy for the treatment of hematological malignancies where the PI3K/Akt signaling pathway is hyperactive. Herein, a series of quinazoline derivatives bearing acrylamide fragment were prepared using skeleton-deconstruction strategy. The preliminary bioactivity evaluation resulted in the discovery of lead compound 15c. Compound 15c exhibited excellent enzyme activity against PI3Kδ (IC50 = 27.5 nM) compared with BEZ235 as well as the significant anti-proliferation activities. With the high selectivity over other PI3K isoforms and potent effects on PI3K/Akt pathway, 15c can be identified as a promising PI3Kδ inhibitor worthy of further profiling.
