Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 35053, Taiwan, ROC.
J Med Chem. 2010 Mar 25;53(6):2409-17. doi: 10.1021/jm901501s.
2-Amino-1-arylidenaminoimidazoles, a novel class of orally (po) active microtubule-destabilizing anticancer agents, were synthesized. The compounds were designed from a hit compound identified in a drug discovery platform by using cancer cell-based high throughput screening assay. Selective synthesized compounds exerted cell cytotoxicity against human cancer cells. The underlying mechanisms for the anticancer activity were demonstrated as interacting with the tubulins and inhibiting microtubule assembly, leading to proliferation inhibition and apoptosis induction in the human tumor cells. Furthermore, two compounds showed in vivo anticancer activities in both po and intravenously (iv) administered routes and prolonged the life spans of murine leukemic P388 cells-inoculated mice. These new po active antimitotic anticancer agents are to be further examined in preclinical studies and developed for clinical uses.
2-氨基-1-芳亚氨基咪唑类化合物是一类新型的具有口服（po）活性的微管不稳定的抗癌药物，已经被合成。这些化合物是通过使用基于癌细胞的高通量筛选方法，从药物发现平台中鉴定的一个先导化合物设计而来的。经过选择性合成的化合物对人类癌细胞表现出细胞毒性。抗癌活性的潜在机制被证明是与微管蛋白相互作用并抑制微管组装，从而导致人类肿瘤细胞的增殖抑制和凋亡诱导。此外，两种化合物在口服和静脉（iv）给药途径中均显示出体内抗癌活性，并延长了白血病 P388 细胞接种小鼠的寿命。这些新的具有口服活性的抗有丝分裂抗癌药物将在临床前研究中进一步进行检查，并开发用于临床应用。
