Comparison between amine-terminated phthalocyanines and their chlorambucil conjugates: Synthesis, spectroscopic properties, and in vitro anticancer activity

• Published in: Tetrahedron 2017-01, Vol.73 (4), p.378-384
• Main Authors: Peng, Xiao-Hui, Chen, Shao-Fang, Zheng, Bi-Yuan, Zheng, Bing-De, Zheng, Qiao-Feng, Li, Xing-Shu, Ke, Mei-Rong, Huang, Jian-Dong
• Format: Article
• Language: English
• Subjects: Anticancer; Chlorambucil; Photodynamic therapy; Phthalocyanine; Structure-activity relationship
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2016.12.017

Two amine-terminated phthalocyanines, including mono-α-substituted zinc phthalocyanine (ZnPc) 4 and axially di-substituted silicon phthalocyanine (SiPc) 6, as well as their chlorambucil (CLB) conjugates (5 and 7) have been prepared. Both 4 and 6 show very high photocytotoxicities against HepG2 cells with IC50 values down to 31 nM and 9 nM, respectively. However, after conjugating with CLB, the anticancer activities of both conjugates, ZnPc-CLB 5 (IC50 = 0.20 μM) and SiPc-CLB 7 (IC50 = 17.47 μM), are greatly reduced as a result of their lower efficiency in fluorescence emission and singlet oxygen generation in aqueous solution. Moreover, both conjugates show significantly lower cellular uptake than their precursors, 4 and 6. Synergetic chemo-photodynamic therapy could not be observed on the two conjugates. [Display omitted] •Two novel phthalocyanine-CLB conjugates (5 and 7) have been synthetized.•The structure-activity relationships of these compounds have been discussed.•6 and 7 show weaker singlet oxygen generation efficiency than that of 4 and 5.•Compound 6 shows the highest photocytotoxicity against HepG2 cells (IC50 = 9 nM).