A step further in the discovery of phthalein derivatives as Thymidylate Synthase inhibitors

被引:10
作者
Calò, S
Tondi, D
Venturelli, A
Ferrari, S
Pecorari, P
Rinaldi, M
Ghelli, S
Costi, MP [1 ]
机构
[1] Univ Modena & Reggio Emilia, Dipartimento Sci Farmaceut, Via Campi 183, I-41100 Modena, Italy
[2] Spinlab Srl, I-42048 Rubiera, RE, Italy
关键词
3H-isobenzofuran-1-one derivatives; enzyme inhibition; Thymidylate Synthase;
D O I
10.3998/ark.5550190.0005.533
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Phenolphthalein (Pth) was discovered as a low micromolar inhibitor of the enzyme Thymidylate Synthase (TS), an important target for anticancer chemotherapy. In the present work, a new series of Pth derivatives have been designed and synthesized. All the compounds have been characterized through NMR techniques. A set of twelve Pth derivatives has been tested against three TS enzymes and their bio-profiles obtained. The bio-profiling studies suggest that the inhibitory potency of the compounds has been improved of about fifty times against Lactobacillus casei TS (LcTS) and five times against humant TS (hTS) with respect to the lead. The most active compound shows an inhibition constant (K-i) of 70 nM against Escherichia coli TS (EcTS).
引用
收藏
页码:382 / 396
页数:15
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