5190-68-1Relevant articles and documents
Potential of substituted quinazolines to interact with multiple targets in the treatment of cancer
Choudhary, Shruti,Doshi, Arpit,Luckett-Chastain, Lerin,Ihnat, Michael,Hamel, Ernest,Mooberry, Susan L.,Gangjee, Aleem
, (2021)
The efficacy of quinazoline-based antiglioma agents has been attributed to their effects on microtubule dynamics.1,2 The design, synthesis and biological evaluation of quinazolines as potent inhibitors of multiple intracellular targets, including microtubules and multiple RTKs, is described. In addition to the known ability of quinazolines 1 and 2 to cause microtubule depolymerization, they were found to be low nanomolar inhibitors of EGFR, VEGFR-2 and PDGFR-β. Low nanomolar inhibition of EGFR was observed for 1–3 and 9–10. Compounds 1 and 4 inhibited VEGFR-2 kinase with activity better than or equal to that of sunitinib. In addition, compounds 1 and 2 had similar potency to sunitinib in the CAM angiogenesis assay. Multitarget activities of compounds in the present study demonstrates that the quinazolines can affect multiple pathways and could lead to these agents having antitumor potential caused by their activity against multiple targets.
Discovery of a Series of Hydroxamic Acid-Based Microtubule Destabilizing Agents with Potent Antitumor Activity
Bai, Peng,Chen, Lijuan,Kuang, Shuang,Liu, Jiang,Liu, Yan,Qiu, Qiang,Shi, Mingsong,Si, Wenting,Su, Zhengying,Tang, Minghai,Yan, Wei,Yang, Jianhong,Yang, Linyu,Yang, Zhuang,Ye, Haoyu,Zhang, Wanhua,Zhu, Zejiang
, p. 15379 - 15401 (2021/11/01)
Hydroxamic acid group is one of the characteristic pharmacophores of histone deacetylase (HDAC) inhibitors. But here, we discovered a series of hydroxamic acid-based microtubule destabilizing agents (MDAs), which were derived from shortening the length of the linker in HDAC6 inhibitor SKLB-23bb. Interestingly, the low nanomolar antiproliferative activity of these MDAs depended on the presence of hydroxamic acid groups, but their inhibitory effects on HDAC were lost. Among them, 12b showed favorable metabolism stability, high bioavailability, and potent antitumor activity in multidrug-resistant cell lines and A2780/T xenograft model. More importantly, in the patient-derived xenograft models of triple-negative breast cancer and osimertinib-resistant non-small-cell lung cancer, both 20 mg/kg oral and 10 mg/kg intravenous administration of 12b could induce more than 70% tumor inhibition without obvious toxicity. Overall, we discovered that 12b, as a novel MDA based on hydroxamic acid, could serve as a potential MDA for further investigation.
Preparation and application of substituted pyrazole compound containing pyriminostrobin
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, (2021/10/20)
The invention discloses a substituted pyrazole compound containing pyrimidine amine as shown in a general formula I. The definition of each substituent in the formula is described in the description. The compounds of the invention have a broad spectrum of sterilization. The insecticidal acaricidal activity has an excellent control effect on cucumber downy mildew, wheat powdery mildew, corn rust, rice blast, cucumber anthracnose and the like. The compounds of the invention exhibit good insecticidal activity at the same time.
Design, Synthesis, Antibacterial Activity, and Mechanisms of Novel 1,3,4-Thiadiazole Derivatives Containing an Amide Moiety
Wu, Zhibing,Shi, Jin,Chen, Jixiang,Hu, Deyu,Song, Baoan
, p. 8660 - 8670 (2021/08/20)
To discover novel antibacterial agents, a series of novel 1,3,4-thiadiazole derivatives containing an amide moiety were designed and synthesized, and their antibacterial activities were tested. Compound 30 was designed and synthesized according to the CoMFA model. Compound 30 exhibited higher antibacterial activities against Xanthomonas oryzae pv. oryzicola and Xanthomonas oryzae pv. oryzae, with EC50 values of 2.1 and 1.8 mg/L, respectively, which were superior to those of thiodiazole copper (99.6 and 92.5 mg/L). The protective and curative activities of compound 30 against rice bacterial leaf blight were 51.3 and 46.1%, respectively, which were better than those of thiodiazole copper (37.8 and 38.5%). The protective and curative activities of compound 30 against rice bacterial leaf streak were 45.9 and 40.5%, respectively, which were better than those of thiodiazole copper (36.2 and 31.1%). In addition, the protective activity of compound 30 against rice bacterial leaf streak was related to increased activities of related defense enzymes and upregulated the differentially expressed proteins of the glycolysis/gluconeogenesis pathway.
