Dark and Photoinduced Cytotoxicity of Chlorophyll a Derivatives and Their Analogues towards HeLa Cells: Some Structure - Activity Relationships

In the present work, we have systematically studied the dark and photoinduced cytotoxicity of a series of chlorophyll a derivatives (a sampling of 36 compounds, the quantitative measure of toxicity is HeLa cell survival and IC50 value) in experiments in vitro. It has been shown that chlorins without an exocycle, such as chlorin e6, its 15,17-dimethyl ether and 13-amide derivatives, regardless of the substituent at the 13-amide nitrogen atom, as well as substituents in positions 3, 15 and 17, as a rule, have the highest cytotoxicity (IC50(dark) < 10 mu M). It has been established that the IC50 value during the dark exposure is more than 10 mu M for the most part of phorbin derivatives, and the presence of polar substituents, such as carboxyl group and 1,2-dihydroxyethyl substituent, on the periphery of the phorbin mac-rocycle leads to an increase in toxicity (IC50(dark) < 10 mu M ). Most of the investigated derivatives of chlorophyll a shows an apparent photodynamic effect on HeLa cells at a concentration of 1 mu M. A more detailed study of com-pounds with different dark toxicity showed that substances with both high and low dark toxicity have high IC50(dark)/IC50(photo) values, so the effectiveness of the photosensitizer is not unambiguously associated with its low dark toxicity.