Kondaskar Atul, Kondaskar Shilpi, Kumar Raj, Fishbein James C, Muvarak Nidal, Lapidus Rena G, Sadowska Mariola, Edelman Martin J, Bol Guus M, Vesuna Farhad, Raman Venu, Hosmane Ramachandra S
Laboratory for Drug Design & Synthesis, Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland, 21250, USA.
ACS Med Chem Lett. 2010 Dec 31;2(3):252-256. doi: 10.1021/ml100281b.
Synthesis of a series of novel, broad-spectrum anti-cancer agents containing the tricyclic 5:7:5-fused diimidazo[4,5-d:4',5'-f][1,3]diazepine ring system is reported. Compounds 1, 2, 8, 11, and 12 in the series show promising in vitro antitumor activity with low micromolar IC(50)'s against prostate, lung, breast, and ovarian cancer cell lines. Some notions about structure-activity relationships and a possible mechanism of biological activity are presented. Also presented are preliminary in vivo toxicity studies of 1 using SCID mice.
报道了一系列含有三环5:7:5-稠合二咪唑并[4,5-d:4',5'-f][1,3]二氮杂卓环系统的新型广谱抗癌剂的合成。该系列中的化合物1、2、8、11和12在体外对前列腺癌、肺癌、乳腺癌和卵巢癌细胞系显示出有前景的抗肿瘤活性，其半数抑制浓度（IC50）为低微摩尔浓度。提出了一些关于构效关系和生物活性可能机制的观点。还介绍了化合物1对重症联合免疫缺陷（SCID）小鼠的初步体内毒性研究。
