Loading…

Synthesis, Tumor Specificity, and Photosensitizing Efficacy of Erlotinib-Conjugated Chlorins and Bacteriochlorins: Identification of a Highly Effective Candidate for Photodynamic Therapy of Cancer

Erlotinib was covalently linked to 3-(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) and structurally related chlorins and bacteriochlorins at different positions of the tetrapyrrole ring. The functional consequence of each modification was determined by quantifying the uptake and subcell...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2021-01, Vol.64 (1), p.741-767
Main Authors: Cheruku, Ravindra R, Cacaccio, Joseph, Durrani, Farukh A, Tabaczynski, Walter A, Watson, Ramona, Siters, Kevin, Missert, Joseph R, Tracy, Erin C, Dukh, Mykhaylo, Guru, Khurshid, Koya, Richard C, Kalinski, Pawel, Baumann, Heinz, Pandey, Ravindra K
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Erlotinib was covalently linked to 3-(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) and structurally related chlorins and bacteriochlorins at different positions of the tetrapyrrole ring. The functional consequence of each modification was determined by quantifying the uptake and subcellular deposition of the erlotinib conjugates, cellular response to therapeutic light treatment in tissue cultures, and in eliminating of corresponding tumors grown as a xenograft in SCID mice. The experimental human cancer models the established cell lines UMUC3 (bladder), FaDu (hypopharynx), and primary cultures of head and neck tumor cells. The effectiveness of the compounds was compared to that of HPPH. Furthermore, specific functional contribution of the carboxylic acid side group at position 17 and the chiral methyl group at 3(1') to the overall activity of the chimeric compounds was assessed. Among the conjugates investigated, the PS was identified as the most effective candidate for achieving tumor cell-specific accumulation and yielding improved long-term tumor control.
ISSN:0022-2623
1520-4804
1520-4804
DOI:10.1021/acs.jmedchem.0c01735