Open AccessChiral Alkyl Groups at Position 3(1′) of Pyropheophorbide-a Specify Uptake and Retention by Tumor Cells and Are Essential for Effective Photodynamic Therapy
Author(s) -
Ravindra R. Cheruku,
Erin Tracy,
Walter A. Tabaczynski,
Joseph R. Missert,
Heinz Baumann,
Ravindra K. Pandey
Publication year - 2021
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.0c02090
Subject(s) - chemistry , thioether , chirality (physics) , ether , photodynamic therapy , alkyl , stereochemistry , in vivo , side chain , carboxylic acid , methyl group , in vitro , biochemistry , organic chemistry , chiral symmetry breaking , physics , microbiology and biotechnology , quantum mechanics , nambu–jona lasinio model , biology , quark , polymer
To investigate the importance of the chirality and precise structure at position 3(1') of pyropheophorbide-a for tumor cell specificity and photodynamic therapy (PDT), a series of photosensitizers (PSs) was synthesized: (a) with and without chirality at position 3(1'), (b) alkyl ether chain with a variable number of chiral centers, (c) hexyl ether versus thioether side chain, and (d) methyl ester versus carboxylic acid group at position 17 2 . The cellular uptake and specificity were defined in human lung and head/neck cancer cells. PSs without a chiral center and with an alkyl chain or thioether functionalities showed limited uptake and PDT efficacy. Replacing the methyl group at the chiral center with a propyl group or introducing an additional chiral center improved cellular retention and tumor cell specificity. Replacing the carboxylic acid with methyl ester at position 17 2 lowered cellular uptake and PDT efficacy. A direct correlation between the PS uptake in vitro and in vivo was identified.