16024-82-1Relevant articles and documents
Novel quinazoline derivatives bearing a sulfapyridine moiety as anticancer and radiosensitizing agents
Ghorab, Mostafa M.,Ragab, Fatma A.,Heiba, Helmi I.,Bayomi, Ahmad A.
, p. E255-E262 (2014)
Quinazoline derivatives posses many types of biological activities and have recently been reported to show substantial antitumor activity in vitro and/or in vivo. There is a variety of mechanisms for their anticancer activity. The present work reports the possible utility of methyl anthranilate in the synthesis of some new quinazoline derivatives, bearing a substituted sulfonamide moiety. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human liver cancer cell line, using doxorubicin as a reference drug. In addition, the most active compounds 14 and 15 were selected and evaluated for their ability to enhance the cell killing effect of γ-radiation.
Identification of Novel Fused Heteroaromatics-Based MALT1 Inhibitors by High-Throughput Screening to Treat B Cell Lymphoma
Liang, Xuewu,Sun, Chenxia,Li, Chunpu,Yu, Haolan,Wei, Xiaohui,Liu, Xuyi,Bao, Wei,Shi, Yuqiang,Sun, Xiaochen,Khamrakulov, Mirzadavlat,Yang, Chenghua,Liu, Hong
, p. 9217 - 9237 (2021/07/20)
Development of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitors is of great value and significance in the treatment of neoplastic disorders and inflammatory and autoimmune diseases. However, there is a lack of effective MALT1 inhibitors in clinic. Herein, a novel class of potent 5-oxo-1-thioxo-4,5-dihydro-1H-thiazolo[3,4-a]quinazoline-based MALT1 inhibitors and their covalent derivatives were first identified and designed through high-throughput screening. We demonstrated that compounds 15c, 15e, and 20c effectively inhibited the MALT1 protease and displayed selective cytotoxicity to activated B cell-like diffuse large B cell lymphoma with low single-digit micromolar potency. Furthermore, compound 20c specifically repressed NF-κB signaling and induced cell apoptosis in MALT1-dependent TMD8 cells in a dose-dependent manner. More importantly, 20c showed good pharmacokinetic properties and antitumor efficacy with no significant toxicity in the TMD8 xenograft tumor model. Collectively, this study provides valuable lead compounds of MALT1 inhibitors for further structural optimization and antitumor mechanism study.
Synthesis of triazoloquinazolinone based compounds as tubulin polymerization inhibitors and vascular disrupting agents
Driowya, Mohsine,Leclercq, Julien,Verones, Valerie,Barczyk, Amélie,Lecoeur, Marie,Renault, Nicolas,Flouquet, Nathalie,Ghinet, Alina,Berthelot, Pascal,Lebegue, Nicolas
, p. 393 - 405 (2016/04/06)
A series of 1-phenyl-[1,2,4]triazolo[4,3-a]quinazolin-5-ones designed as conformationally restricted CA-4 analogues, were tested for their tubulin polymerization and growth inhibitory activities. The 3-hydroxy-4-methoxy derivatives 11d and 12d are potent inhibitors of tubulin assembly but only the N-methylated amid counterpart 12d possesses potent anticancer activity in a large panel of cancer cell lines. Upon treatment with compound 12d, remarkable cell shape changes as cell migration and tube formation were elicited in HUVECs, consistent with vasculature damaging activity.
