title: Synthesis and antitumor activity of 5-[1-(3-(dimethylamino)propyl)-5-halogenated-2-oxoindolin-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxamides.
abstract: We report herein the design and synthesis of novel 1-[3-(dimethylamino)propyl]indolin-2-one derivatives based on the structural features of Sunitinib, a known multitargeted receptor tyrosine kinase inhibitor, and TMP-20, a previously discovered compound with good antitumor activity in our lab. These newly synthesized derivatives were evaluated for in vitro activity against five human cancer cell lines and VEGF/bFGF-stimulated HUVECs. Results revealed that all of the target compounds 1a-p show potent antitumor activity, compounds 1e-h (IC(50)'s: 0.45-5.08 μM) are more active than Sunitinib (IC(50)'s: 1.35-6.61 μM), and the most active compound 1 h (IC(50): 0.47-3.11 μM) is 2.1-4.6-fold more potent than Sunitinib against all five cancer cell lines. In addition, like Sunitinib, 1a-p have higher selectivity on VEGF-stimulated HUVEC other than bFGF-stimulated HUVEC.
authors: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors: Kai
authors: K
authors: Lv
authors: Li-Li
authors: LL
authors: Wang
authors: Ming-Liang
authors: ML
authors: Liu
authors: Xin-Bo
authors: XB
authors: Zhou
authors: Shi-Yong
authors: SY
authors: Fan
authors: Hong-Ying
authors: HY
authors: Liu
authors: Zhi-Bing
authors: ZB
authors: Zheng
authors: Song
authors: S
authors: Li
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006219:Halogens / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry; D000077210:Sunitinib
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D006219:Halogens; D007211:Indoles; D011758:Pyrroles; C456900:indolin-2-one; D000077210:Sunitinib