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

Autor:	Cheruku RR; PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14223, United States., Cacaccio J; PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14223, United States., Durrani FA; PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14223, United States., Tabaczynski WA; PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14223, United States., Watson R; PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14223, United States., Siters K; Photolitec, LLC, 73 High Street, Buffalo, New York 14223, United States., Missert JR; PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14223, United States., Tracy EC; Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14263, United States., Dukh M; PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14223, United States., Guru K; Department of Urology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14263, United States., Koya RC; Department of Immunology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14263, United States., Kalinski P; Department of Immunology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14263, United States., Baumann H; Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14263, United States., Pandey RK; PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center Buffalo, Buffalo, New York 14223, United States.
Jazyk:	angličtina
Zdroj:	Journal of medicinal chemistry [J Med Chem] 2021 Jan 14; Vol. 64 (1), pp. 741-767. Date of Electronic Publication: 2021 Jan 05.
DOI:	10.1021/acs.jmedchem.0c01735
Abstrakt:	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 2 and the chiral methyl group at 3(1') to the overall activity of the chimeric compounds was assessed. Among the conjugates investigated, the PS 10 was identified as the most effective candidate for achieving tumor cell-specific accumulation and yielding improved long-term tumor control.
Databáze:	MEDLINE
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