Gul Halise I, Yerdelen Kadir O, Gul Mustafa, Das Umashankar, Pandit Bulbul, Li Pui-Kai, Secen Hasan, Sahin Fikrettin
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
Arch Pharm (Weinheim). 2007 Apr;340(4):195-201. doi: 10.1002/ardp.200600072.
A new series of mono Mannich bases of 4'-hydroxychalcones 2a-e carrying a variety of aryl groups was synthesized and the in vitro cytotoxic activities of the new compounds were screened against PC-3 cell lines. Bioactivities of 2a-e, which are reported for the first time in this study, were compared against their precursor 4'-hydroxychalcones 1a-e. Compound 2b was found to be the most potent (IC(50 )= 3.7 microM) among the compounds synthesized. In addition, the compounds 1a-c and 2d showed moderate cytotoxicity. Incorporation of the 3'-piperidinomethyl group in 1b and 1d raised the potency by 1.68 and 2.19 times respectively and, therefore, seemed to be a noteworthy molecular modification. Correlations were noted between cytotoxicity and one or more physiochemical constants of the aryl ring as well as log P values for the compounds 2a-e. The significant improvement of cytotoxicity of 2b, 2d, and 2e against PC-3 cell lines compared with their chalcone precursors suggests that the incorporation of a piperidinomethyl group is a useful molecular modification and further development of these compounds as candidate cytotoxic agents may be warranted.
合成了一系列带有各种芳基的新型4'-羟基查尔酮2a - e的单曼尼希碱，并针对PC - 3细胞系筛选了这些新化合物的体外细胞毒性活性。将本研究首次报道的2a - e的生物活性与其前体4'-羟基查尔酮1a - e进行了比较。发现化合物2b在所合成的化合物中活性最强（IC(50)=3.7 microM）。此外，化合物1a - c和2d表现出中等细胞毒性。在1b和1d中引入3'-哌啶甲基分别使活性提高了1.68倍和2.19倍，因此似乎是一种值得注意的分子修饰。观察到细胞毒性与芳环的一个或多个物理化学常数以及化合物2a - e的log P值之间存在相关性。与它们的查尔酮前体相比，2b、2d和2e对PC - 3细胞系的细胞毒性显著提高，这表明引入哌啶甲基是一种有用的分子修饰，可能有必要进一步开发这些化合物作为候选细胞毒性剂。
