Conjugates of Pyropheophorbide a with 17-Substituted Steroidal Androgens. Synthesis, Molecular Modeling, Interaction with Some Cancer Cells

Five new bifunctional conjugates of pyropheophorbide a with 17-substituted testosterone, dihydrotestosterone and epitestosterone differing in the length linker (1 � 5) two complex 6 7 (containing three functional units: a, 17?-substituted lipophylic hexadecyl chain, connected L-lysine joining block) were synthesized. Mutual influence steroidal macrocyclic fragments 7) was established by analysis 1H NMR spectra molecular models conjugates. Studies interaction 1 5 prostate carcinoma cells revealed that their uptake internalization dependent on structure conjugates, particularly stereochemical configuration 17-hydroxyl group moiety, connecting steroid fragments. Conjugates significantly decreased growth proliferation LNCaP PC-3 cells. The highest anti-proliferative activity demonstrated derivative 3, comprising short linker. Irradiation labeled light (? = 660 nm) increased cytotoxicity. Trifunctional easily formed mixed micells phosphatidyl choline pluronic F68; these micelles efficiently internalized human hepatocarcinoma Hep G2 binding form to depended conjugate structure, rather than method solubilization.