Introduction. For photodynamic therapy (PDT), special attention is paid to photosensitizers (PS) based on chlorins and their derivatives, synthetic analogues of natural pigments that combine powerful photoactivity with the possibility of subtle chemical modification. The main advantages of chlorin photosensitizers are their intense absorption in the long-wavelength region of the spectrum (650–750 nm), providing deep penetration of light into biological tissues, high quantum yield of singlet oxygen generation and the ability to selectively accumulate in pathological foci. Reduced derivatives of chlorin imides are of particular interest in this context, as they have greater stability under physiological conditions.
Methods. N-hydroxy and N-methoxy derivatives of purpurinimide-18 methyl ester were selected as the starting compounds. The obtained derivatives were purified by means of preparative chromatography. The structures of the obtained compounds were confirmed using a complex of modern physico-chemical analysis methods: electron and fluorescence spectroscopy, mass spectrometry, and 1H- and 13C NMR spectroscopy.
Results. In this work, strategies for the reduction of the “exocycle E” of N -methoxy purpurinimide-18 were developed. The resulting derivative had an absorption maximum in the long-wave region of the visible spectrum (656 nm), as well as a three-fold higher quantum yield of singlet oxygen generation compared to the original compound.
Conclusions. The resulting reduced imide derivative combines absorption in the therapeutic window (656 nm) and high photoactivity (compared to the parent compound). The reduction of carbonyl groups of exocycle E can lead to an improvement in pharmacokinetic parameters and a more effective modification of the nitrogen atom. This compound is a promising candidate for the development of new effective drugs for PDT.
The work was carried out with the support of the Ministry of Science and Higher Education of the Russian Federation (government assignment №075-00727-25-05 dated 20/03/2025; FSFZ-2024-0013).
