Premium
Photophysical and photobiological behaviour of antimalarial drugs in aqueous solutions
Author(s) -
Aloisi Gian Gaetano,
Barbafina Arianna,
Canton Marcella,
Dall'Acqua Francesco,
Elisei Fausto,
Facciolo Laura,
Latterini Loredana,
Viola Giampietro
Publication year - 2004
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2004.tb00392.x
Subject(s) - phototoxicity , chemistry , flash photolysis , photochemistry , quantum yield , intersystem crossing , aqueous solution , fluorescence , excited state , biophysics , organic chemistry , in vitro , biochemistry , kinetics , quantum mechanics , physics , nuclear physics , reaction rate constant , singlet state , biology
This article describes the results of a combined photophysical and photobiological study aimed at understanding the phototoxicity mechanism of the antimalarial drugs quinine (Q), quinacrine (QC) and mefloquine (MQ). Photophysical experiments were carried out in aqueous solutions by stationary and time‐resolved fluorimetry and by laser flash pbotolysis to obtain information on the various decay pathways of the excited states of the drugs and on transient species formed on irradiation. The results obtained showed that fluorescence and intersystem crossing account for all the adsorbed quanta for Q and MQ (quantum yield of about 0.1 and 0.9, respectively) and only for 24% in the case of QC, which has a negligible fluorescence quantum yield (0.001). Laser flash photolysis experiments evidenced, for QC and, MQ, the occurrence of photoionization processes leading to the formation of the radical cations of the drugs. The effects of tryptophan and histidine on the excited states and transient species of the three drugs were also investigated. In parallel, the photoactivity of the antimalarial drugs was investigated under UV irradiation on various biological targets through a series of in vitro assays in the presence and in the absence of oxygen. Phototoxicity on 3T3 cultured fibroblasts and lipid photoperoxidation were observed for all the drugs. The photodamage produced by the drugs was also evaluated on proteins by measuring the photosensitized cross‐linking of spectrin. The combined approaches were proven to be usefulfor understanding the mechanism of phototoxicity induced by the antimalarial drugs.