Ibuprofen and ketoprofen potentiate UVA-induced cell death by a photosensitization process

Abstract

Nonsteroidal 2-arylproprionic acids are widely used, over-the-counter, anti-inflammatory drugs. Photosensitivity is a commonly overlooked adverse effect of these drugs. Based on the combined use of cell viability assays and molecular modeling, we prove and rationalize the photochemical pathways triggering photosensitization for two drugs, ibuprofen and ketoprofen. As its parent compound benzophenone, ketoprofen produces singlet oxygen, upon triplet manifold population. However, ibuprofen and ketoprofen photodissociate and hence may generate two highly reactive radicals. The formation of metastable aggregates between the two drugs and B-DNA is also directly probed by molecular dynamics. Our approach characterizes the coupled influence of the drug’s intrinsic photochemistry and the interaction pattern with DNA. The photosensitization activity of nonsteroidal 2-arylproprionic acids, being added to gels and creams for topical use, should be crucially analyzed and rationalized to enact the proper preventive measures.

Regioselective Synthesis of Arylsulfonyl Benzophenones via Aerobic Oxidative [3+3] Benzannulation Reactions

“…A representative selection of natural and designed benzophenones that are bioactive, marketed as drugs or used as sun‐protection agents is depicted in Figure 1. Phenstatin is a potent anticancer agent that works by inhibiting tubulin polymerization, [ 2 ] cariphenone is a naturally occurring antioxidant, [ 3 ] ketoprofen is a non‐steroidal anti‐inflammatory drug (NSAID), [ 4 ] tolcapone is a drug used for the treatment of Parkinson's disease (sold under the brand name Tasmar) [ 5 ] and fenofibrate is a drug that lowers blood lipid levels. [ 6 ] Sulisobenzone (also known as benzophenone‐4), a sulfonylated benzophenone that is the active ingredient responsible for UV protection in some sunscreens is another notable example.…”

Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA

“…Non-covalent DNA adducts can be highly stable and persistent, and, in some cases, lead to replication blockage and apoptosis. In addition to this role, they can act as photosensitizers and exacerbate the toxicity of other stress sources, such as UV light or ionizing radiation [ 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Sensitizers can act either via the production of O [ 36 ], via energy transfer, usually from the triplet manifold [ 28 , 30 , 37 , 38 ], or via electron transfer, usually towards guanine [ 39 , 40 ].…”

“…Sensitizers can act either via the production of O [ 36 ], via energy transfer, usually from the triplet manifold [ 28 , 30 , 37 , 38 ], or via electron transfer, usually towards guanine [ 39 , 40 ]. Moreover, photosensitizers may also trigger photochemical reactions, leaving reactive radicals in close proximity to the DNA, capable of further inducing deleterious reactions such as hydrogen abstraction or strand breaks [ 29 , 35 , 41 ].…”

Ketoprofen Combined with UVA Irradiation Exerts Higher Selectivity in the Mode of Action against Melanotic Melanoma Cells than against Normal Human Melanocytes

“…Topical ketoprofen is used to cure the pain and inflammation illnesses such as tendonitis, small joint osteoarthritis, back pain, phlebitis, and acute minor trauma (sprains, bruising) [ 15 , 16 ]. Moreover, the phototoxic effect of ketoprofen has been demonstrated in relation to breast cancer cells, where co-therapy using ketoprofen and UVAR caused a meaningful reduction of cell viability [ 17 ].…”