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Photophysical Studies on Antimalariai Drugs
Author(s) -
Morten Ann G.,
Martinez Lydia J.,
Holt Nathan,
Sik Robert H.,
Reszka Krzysztof,
Chignell Colin F.,
Tonnesen Hanne H.,
Roberts Joan E.
Publication year - 1999
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.1751-1097.1999.tb03287.x
Subject(s) - chemistry , primaquine , hydroxychloroquine , photochemistry , quinine , amodiaquine , adduct , mefloquine , chloroquine , medicine , organic chemistry , malaria , disease , covid-19 , pathology , infectious disease (medical specialty) , immunology
— Most drugs used in the treatment of malaria produce phototoxic side effects in both the skin and the eye. Cutaneous and ocular effects that may be caused by light include changes in skin pigmentation, corneal opacity, cataract formation and other visual disturbances including irreversible retinal damage (retinopathy) leading to blindness. The mechanism for these reactions in humans is unknown. We irradiated a number of antimalarial drugs (amodiaquine, chloroquine, hydroxychloroquine, mefloquine, primaquine and quinacrine) with light (Λ > 300 nm) and conducted electron paramagnetic resonance (EPR) and laser flash photolysis studies to determine the possible active intermediates produced. Each antimalarial drug produced at least one EPR adduct with the spin‐trap 5,5‐dimethyl‐l‐pyrroline N ‐oxide in benzene: superoxide/hydroperoxyl adducts (chloroquine, mefloquine, quinacrine, amodiaquine and quinine), carbon‐centered radical adducts (all but primaquine), or a nitrogen‐centered radical adduct only (primaquine). In ethanol all drugs except primaquine produced some superoxide/hydroperoxyl adduct, with quinine, quinacrine, and hydroxychloroquine also producing the ethoxyl adduct. As detected with flash photolysis and steady‐state techniques, mefloquine, quinine, amodiquine and a photoproduct of quinacrine produced singlet oxygen (τ= 0.38; τ= 0.36; τ= 0.011; τ= 0.013 in D 2 O, pD7), but only primaquine quenched singlet oxygen efficiently (2.6 × 10 8 M −1 s 1 in D 2 O, pD7). Because malaria is a disease most prevalent in regions of high light intensity, protective measures (clothing, sunblock, sunglasses or eye wraps) should be recommended when administering antimalarial drugs.