3817-05-8Relevant articles and documents
In Vivo and Mechanistic Studies on Antitumor Lead 7-Methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin-2(1H)-one and Its Modification as a Novel Class of Tubulin-Binding Tumor-Vascular Disrupting Agents
Cui, Mu-Tian,Jiang, Li,Goto, Masuo,Hsu, Pei-Ling,Li, Linna,Zhang, Qi,Wei, Lei,Yuan, Shou-Jun,Hamel, Ernest,Morris-Natschke, Susan L.,Lee, Kuo-Hsiung,Xie, Lan
, p. 5586 - 5598 (2017)
7-Methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin-2(1H)-one (2), a promising anticancer lead previously identified by us, inhibited tumor growth by 62% in mice at 1.0 mg/kg without obvious signs of toxicity. Moreover, compound 2 exhibited extremely high antiproliferative activity in the NIH-NCI 60 human tumor cell line panel, with low to sub-nanomolar GI50 values (10-10 M level). It also showed a suitable balance between aqueous solubility and lipophilicity, as well as moderate metabolic stability in vivo. Mechanistic studies using Mayer's hematoxylin and eosin and immunohistochemistry protocols on xenograft tumor tissues showed that 2 inhibited tumor cell proliferation, induced apoptosis, and disrupted tumor vasculature. Moreover, evaluation of new synthetic analogues (6a-6t) of 2 indicated that appropriate 2-substitution on the quinazoline ring could enhance antitumor activity and improve druglike properties. Compound 2 and its analogues with a 4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin-2(1H)-one scaffold thus represent a novel class of tubulin-binding tumor-vascular disrupting agents (tumor-VDAs) that target established blood vessels in tumors.
Quinazolin-4(3H)-one based agents bearing thiadiazole-urea: Synthesis and evaluation of anti-proliferative and antiangiogenic activity
Faraji, Aram,Motahari, Rasoul,Hasanvand, Zaman,Oghabi Bakhshaiesh, Tayebeh,Toolabi, Mahsa,Moghimi, Setareh,Firoozpour, Loghman,Boshagh, Mohammad Amin,Rahmani, Roya,Ketabforoosh, Shima H.M.E.,Bijanzadeh, Hamid Reza,Esmaeili, Rezvan,Foroumadi, Alireza
, (2021/01/04)
A series of quinazolin-4(3H)-one based agents containing thiadiazole-urea were designed, synthesized, and biologically evaluated. The proliferation rate of PC3 cells was moderately reduced by compound 9f (IC50 = 17.7 μM)which was comparable with sorafenib (IC50 = 17.3 μM). There was also a significant reduction in the number of HUVEC cells, when they were exposed to compound 9y (IC50 = 6.1 μM). To test the potential of compounds in inducing apoptosis, Annexin V-FITC/propidium iodide double staining assay was used. After the treatment of HUVEC cells with 9f, they underwent apoptotic effects. A substantial effort was dedicated to gathering comprehensive data across CAM assay. These data showed that 9f moderately inhibits the growth of corresponding blood vessels. Finally, the outcomes of Western blotting proposed a mechanism of action, by which the phosphorylation of VEGFR-2 is inhibited by compounds 9f and 9y.
Synthesis and evaluation of anticancer and PDE 5 inhibitory activity of spiro-substituted quinazolin-4-ones
Ameen, Mohamed A.,Ahmed, Essam Kh.,Ramadan, Mohamed,Abd El-Naby, Hisham A.,Abdel-Haseeb, Asmaa A.
, p. 1513 - 1523 (2017/07/18)
A series of novel spiro-substituted 2,3-dihydroquinazolin-4(1H)-ones was synthesized and structurally confirmed by spectral analysis, screened for their anticancer activity at a concentration of 10 μΜ against a panel of 56 cell lines derived from nine different types of cancers, including leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers. The synthesized compounds screened for their PDE 5 inhibitory activity and it showed encouraged activity compared to sildenafil. Graphical abstract: [Figure not available: see fulltext.].
