Журнал "Макрогетероциклы"

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 (IC_50(dark) < 10 µM). It has been established that the IC₅₀ value during the dark exposure is more than 10 µM 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 macrocycle leads to an increase in toxicity (IC_50(dark) < 10 µM ). Most of the investigated derivatives of chlorophyll a shows an apparent photodynamic effect on HeLa cells at a concentration of 1 µM. A more detailed study of compounds with different dark toxicity showed that substances with both high and low dark toxicity have high IC_50(dark)/IC_50(photo) values, so the effectiveness of the photosensitizer is not unambiguously associated with its low dark toxicity.

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