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Five new bifunctional conjugates of pyropheophorbide a with 17-substituted testosterone, dihydrotestosterone and epitestosterone differing in the length of linker (1–5) and two new complex conjugates 6 and 7 (containing three functional units: pyropheophorbide a, 17α-substituted testosterone, and lipophylic hexadecyl chain) were synthesized. Mutual influence of steroidal and macrocyclic fragments in conjugates 1–7 was established by analysis of 1H NMR spectra and molecular models of conjugates. The uptake and internalization of conjugates 1–5 by prostate carcinoma cells were dependent on the stereochemical configuration of 17-hydroxyl group in steroidal moiety, and the length of linker. Conjugates 1–5 significantly decreased the LNCaP and PC-3 cells growth and proliferation at 96 h incubation; the anti-proliferative activity of epitestosterone derivative comprising short linker 3 was superior. Irradiation of cells labeled with conjugates with light (λ = 660 nm) significantly increased cytotoxicity. Trifunctioal conjugates 6 and 7 easily formed mixed micells with phosphatidyl choline and pluronic F68; these mixed micelles efficiently internalized by human hepatocarcinoma Hep G2 cells, herewith the internalization was dependent on the conjugate structure, rather than on the method of solubilization.

The review discusses the latest advances in the directed synthesis and application of macroheterocyclic compounds in science, engineering and technology, viz. as catalysts for various processes in photo- and electrocatalysis, optical chemosensors for metal cations, selective receptors of organic compounds, inductors and selectors, in nonlinear optics, organic electronics, as magnets, photosensitizers for PDT of a number of oncological diseases and for antimicrobial PDT, etc.