Eight new water-soluble amino acid conjugates 6 a-h of chlorin p6 ethers(5 a-d) were synthesized and preliminarily investigated for their in vitro PDT antitumor activity and structure-activity relationship(SAR). The r...Eight new water-soluble amino acid conjugates 6 a-h of chlorin p6 ethers(5 a-d) were synthesized and preliminarily investigated for their in vitro PDT antitumor activity and structure-activity relationship(SAR). The results showed that all compounds exhibited much higher phototoxicity against tumor cells than talaporfin. SAR analysis indicated that PDT antitumor effect enhanced with the increase of carbon chain length of alkoxyl ether bonds at 3~1-position, and L-aspartic acid was superior to L-glutamic acid. In particular, the IC_50 values of most phototoxic compound 6 d were 0.20 mmol/L against A549 cell and0.41υmmol/L against B16-F10 cell, which individually represented 31-and 24-fold increase of antitumor potency compared to talaporfin, suggesting that it was a promising candidate photosensitizer(PS) for PDT applications due to its strong absorption at long wavelength, high phototoxicity, low dark cytotoxicity and good water-solubility.展开更多
基金supported by grants from the National Natural Science Foundation of China (Nos. 81172950 and 81671739)the Project of Science and Technology Commission of Shanghai (No. 11431920401)the College Students’ Innovation Ability Training Project of Second Military Medical University (No. MS2017040)
文摘Eight new water-soluble amino acid conjugates 6 a-h of chlorin p6 ethers(5 a-d) were synthesized and preliminarily investigated for their in vitro PDT antitumor activity and structure-activity relationship(SAR). The results showed that all compounds exhibited much higher phototoxicity against tumor cells than talaporfin. SAR analysis indicated that PDT antitumor effect enhanced with the increase of carbon chain length of alkoxyl ether bonds at 3~1-position, and L-aspartic acid was superior to L-glutamic acid. In particular, the IC_50 values of most phototoxic compound 6 d were 0.20 mmol/L against A549 cell and0.41υmmol/L against B16-F10 cell, which individually represented 31-and 24-fold increase of antitumor potency compared to talaporfin, suggesting that it was a promising candidate photosensitizer(PS) for PDT applications due to its strong absorption at long wavelength, high phototoxicity, low dark cytotoxicity and good water-solubility.
