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Bioorg Med Chem. 2012 Jul 15;20(14):4472-81. doi: 10.1016/j.bmc.2012.05.028. Epub 2012 May 23.
Nuclear monoamination of a 1,4-naphthohydroquinone with primary aromatic amines was catalysed by the commercial laccase, Novozym 51003, from Novozymes to afford aminonaphthoquinones. The synthesis was accomplished by reacting a mixture of the primary amine and 1,4-naphthohydroquinone in succinate-lactate buffer and a co-solvent, dimethylformamide, under mild reaction conditions in a vessel open to air at pH 4.5 and pH 6.0. Anticancer screening showed that the aminonaphthoquinones exhibited potent cytostatic effects particularly against the UACC62 (melanoma) cancer cell line (GI(50)=3.98-7.54 μM). One compound exhibited potent cytostatic effects against both the TK10 (renal) and the UACC62 (melanoma) cancer cell line. The cytostatic effects of this compound (GI(50)=8.38 μM) against the TK10 cell line was almost as good as that of the anticancer agent, etoposide (GI(50)=7.19μM). Two compounds exhibited potent cytostatic effects against both the UACC62 (melanoma) and the MCF7 (breast) cancer cell lines. The total growth inhibition (TGI) of most of the compounds was better than that of etoposide against the UACC62 cell line. Three compounds (TGI=7.17-7.94 μM) exhibited potent cytostatic effects against the UACC62 cell line which was 7 to 8-fold better than that of etoposide (TGI=52.71 μM). The results are encouraging for further study of the aminonaphthoquinones for potential application in anticancer therapy.
用商业漆酶 Novozym 51003 催化 1,4-萘二酚与伯芳胺的核单胺化反应，合成了氨基萘醌。该合成反应是在琥珀酸-乳酸盐缓冲液和二甲亚砜(co-solvent)中，在 pH4.5 和 pH6.0 下，于开放体系中温和条件下进行的，反应物为 1,4-萘二酚和伯芳胺的混合物。抗癌筛选表明，氨基萘醌对 UACC62(黑色素瘤)癌细胞系具有很强的细胞生长抑制作用(GI(50)=3.98-7.54 μM)。一种化合物对 TK10(肾)和 UACC62(黑色素瘤)癌细胞系都具有很强的细胞生长抑制作用。该化合物对 TK10 细胞系的细胞生长抑制作用(GI(50)=8.38 μM)几乎与抗癌药物依托泊苷(GI(50)=7.19μM)相当。两种化合物对 UACC62(黑色素瘤)和 MCF7(乳腺癌)癌细胞系都具有很强的细胞生长抑制作用。大多数化合物的总生长抑制(TGI)优于依托泊苷对 UACC62 细胞系的抑制作用。三种化合物(TGI=7.17-7.94 μM)对 UACC62 细胞系具有很强的细胞生长抑制作用，其效果是依托泊苷的 7-8 倍(TGI=52.71 μM)。这些结果为进一步研究氨基萘醌在抗癌治疗中的潜在应用提供了令人鼓舞的依据。
