title: Photophysical properties and photobiological behavior of amodiaquine, primaquine and chloroquine.
abstract: This article describes the results of a coupled photophysical and photobiological study aimed at understanding the phototoxicity mechanism of the antimalarial drugs amodiaquine (AQ), primaquine (PQ) and chloroquine (CQ). Photophysical experiments were carried out in aqueous solutions by steady-state and time-resolved spectrometric techniques to obtain information on the different decay pathways of the excited states of the drugs and on the transient species formed upon laser irradiation. The results showed that all three drugs possess very low fluorescence quantum yields (10(-2)-10(-4)). Laser flash photolysis experiments proved the occurrence of photoionization processes leading to the formation of a radical cation in all three systems. In the case of AQ the lowest triplet state was also detected. Together with the photophysical properties the photobiological properties of the antimalarial drugs were investigated under UV irradiation, on various biological targets through a series of in vitro assays. Phototoxicity on mouse 3T3 fibroblast and human keratinocyte cell lines NCTC-2544 was detected for PQ and CQ but not for AQ. In particular, PQ- and CQ-induced apoptosis was revealed by the externalization of phosphatidylserine. Furthermore, upon UV irradiation, the drugs caused significant variations of the mitochondrial potential (Deltapsi(mt)) measured by flow cytometry. The photodamages produced by the drugs were also evaluated on proteins, lipids and DNA. The combined approaches were useful in understanding the mechanism of phototoxicity induced by these antimalarial drugs.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Padova, Padova, Italy. giampietro.viola.1@unipd.it
authors.forename: Giampietro
authors.initials: G
authors.lastname: Viola
authors.forename: Alessia
authors.initials: A
authors.lastname: Salvador
authors.forename: Laura
authors.initials: L
authors.lastname: Cecconet
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Daniela
authors.initials: D
authors.lastname: Vedaldi
authors.forename: Francesco
authors.initials: F
authors.lastname: Dall'Acqua
authors.forename: Gian Gaetano
authors.initials: GG
authors.lastname: Aloisi
authors.forename: Matteo
authors.initials: M
authors.lastname: Amelia
authors.forename: Arianna
authors.initials: A
authors.lastname: Barbafina
authors.forename: Loredana
authors.initials: L
authors.lastname: Latterini
authors.forename: Fausto
authors.initials: F
authors.lastname: Elisei
mesh_terms: D000655:Amodiaquine / Q000737:chemistry* / Q000633:toxicity; D000818:Animals; D000962:Antimalarials; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002738:Chloroquine / Q000737:chemistry* / Q000633:toxicity; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008247:Lysosomes / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000528:radiation effects; D015394:Molecular Structure; D018462:Photobiology; D010777:Photochemistry; D011319:Primaquine / Q000737:chemistry* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D012474:Salmon; D013053:Spectrophotometry
chemical_list: D000962:Antimalarials; D017382:Reactive Oxygen Species; D000655:Amodiaquine; D002738:Chloroquine; D004247:DNA; D011319:Primaquine