Trifunctional (Pyropheophorbide a – Steroid – Hexadecyl Chain) Conjugates: Synthesis, Solubilization, Interaction wit

Maria O. Taratynova,^a Vladimir A. Zolottsev,^a Yaroslav V. Tkachev,^b Roman A. Novikov,^b Maria G. Zavialova,^a Galina E. Morozevich,^a Vladimir P. Timofeev,^b Yulia V. Romanenko,^c Oskar I. Koifman,^c Alexander Y. Misharin,^a and Gelii V. Ponomarev^a@

^aOrekhovich Institute of Biomedical Chemistry, 119121 Moscow, Russia

^bEngelhardt Institute of Molecular Biology RAS, 119991 Moscow, Russia

^cResearch Institute of Macroheterocycles, Ivanovo State University of Chemistry and Technology, 153000 Ivanovo, Russia

^@Corresponding author E-mail: gelii@yandex.ru

DOI: 10.6060/mhc180999p
Macroheterocycles 2018 11(3) 277-285

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.

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Trifunctional (Pyropheophorbide a – Steroid – Hexadecyl Chain) Conjugates: Synthesis, Solubilization, Interaction wit

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