Conjugates of Pyropheophorbide a with 17-Substituted Steroidal Androgens. Synthesis, Molecular Modeling, Interaction with Some Cancer Cells
Open Access
- 1 September 2022
- journal article
- Published by Institute of Biochemistry in Biomedical Chemistry: Research and Methods
- Vol. 5 (3), e00167
- https://doi.org/10.18097/bmcrm00167
Abstract
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, connected with L-lysine joining block) 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. Studies of interaction of conjugates 1 – 5 with prostate carcinoma cells revealed that their uptake and internalization were dependent on the structure of conjugates, particularly on the stereochemical configuration of 17-hydroxyl group in steroidal moiety, and the length of linker connecting pyropheophorbide a with steroid fragments. Conjugates 1 – 5 significantly decreased the growth and proliferation of LNCaP and PC-3 cells. The highest anti-proliferative activity demonstrated by epitestosterone derivative 3, comprising short linker. Irradiation of labeled cells with light (λ = 660 nm) was significantly increased cytotoxicity. Trifunctional 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. The binding of conjugates 6 and 7 in the form of mixed micelles to Hep G2 cells depended on the conjugate structure, rather than on the method of solubilization.Keywords
This publication has 23 references indexed in Scilit:
- Internalization of a C17α-alkynylestradiol-porphyrin conjugate into estrogen receptor positive MCF-7 breast cancer cellsBioorganic & Medicinal Chemistry Letters, 2011
- SwissParam: A fast force field generation tool for small organic moleculesJournal of Computational Chemistry, 2011
- Synthetic approaches for the conjugation of porphyrins and related macrocycles to peptides and proteinsPhotochemical & Photobiological Sciences, 2011
- Covalently linked zinc chlorophyll dimers as a model of a chlorophyllous pair in photosynthetic reaction centersPhotochemical & Photobiological Sciences, 2008
- Synthesis of zinc bacteriochlorophyll-d analogues with various 17-substituents and their chlorosomal self-aggregates in non-polar organic solventsPhotochemical & Photobiological Sciences, 2008
- Synthesis of estradiol-pheophorbide a conjugates: evidence of nuclear targeting, DNA damage and improved photodynamic activity in human breast cancer and vascular endothelial cellsPhotochemical & Photobiological Sciences, 2006
- Scalable molecular dynamics with NAMDJournal of Computational Chemistry, 2005
- VMD: Visual molecular dynamicsJournal of Molecular Graphics, 1996
- Oxidation of octyl α-d-glucopyranoside to octyl α-d-glucuronic acid, catalyzed by several ruthenium complexes, containing a 2-(phenyl)azopyridine or a 2-(nitrophenyl)azopyridine ligandJournal of Molecular Catalysis A: Chemical, 1995
- Synthesis of high-affinity fluorine-substituted ligands for the androgen receptor. Potential agents for imaging prostatic cancer by positron emission tomographyJournal of Medicinal Chemistry, 1992