Trifunctional (Pyropheophorbide a – Steroid – Hexadecyl Chain) Conjugates: Synthesis, Solubilization, Interaction with Cultured Cells

Abstract

Two novel complex conjugates (containing three functional units: pyropheophorbide a, 17α-substituted testosterone, and lipophylic hexadecyl chain, connected with L-lysine joining block) were synthesized. The scheme consisted of condensation of N(α)-Fmoc-N(ε)-Boc-Lys with hexadecyl amine, followed by consecutive removal of N-protective groups and coupling of obtained intermediates either with pyropheophorbide a, or with 17β-hydroxy-3-oxopregn-4-en-21-oic acid. Mutual influence of steroidal and macrocyclic fragments depending on conjugate structure was established by analysis of NMR spectra and molecular models of conjugates. Complex conjugates easily formed mixed micelles with phosphatidyl choline and pluronic F68; these mixed micelles efficiently internalized by human hepatocarcinoma Hep G2 cells, and slightly-by human prostate carcinoma LNCaP cells. The binding of complex conjugates to cells was dependent on the conjugate structure.

Steroid Conjugates as Potential Anti-Cancer Agents

“…легко образующие смешанные мицеллы с фосфатидилхолином и плюроником F68. Эти смешанные мицеллы эффективно интернализовались клетками гепатоцеллюлярной карциномы HepG2 и сла-бо -клетками рака предстательной железы LNCaP, причем интернализация зависела от структуры конъюгата, но не зависела от способа солюбилизации [117].…”