Molecular mechanisms of photosensitization induced by drugs XIV: Two different behaviours in the photochemistry and photosensitization of antibacterials containing a fluoroquinolone like chromophore

Abstract

This paper deals with the photosensitizing activity of FLQs towards two different biosubstrates, membrane and DNA. The in vitro phototoxic activity of these drugs vs. DNA presents peculiar features with respect to that vs. membranes, probably due to a specific binding of the drugs to the double helix and to the operativeness of different photosensitization mechanisms with the two types of biosubstrates. A description of the UVA photochemistry and the photosensitizing properties of two significant examples in the FLQ family is reported. The investigated compounds are Enoxacin, 1-ethyl-6-fluoro-1,4-dihydro-4- oxo-7-[1-piperazinyl]-1,8-naphtyridine-3-carboxilic acid and Rufloxacin, 9-fluoro-2,3-dihydro-10-4´-methyl- 1´-piperazinyl-7-oxo-7H-pyrido[1,2,3−de]-1,4-benzothiazine-6-carboxylic acid

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

“…Cleavage: Almost all FQs have been reported to induce SSB on plasmid DNA: ENO (18,37,52,87,(108)(109)(110)(111), PEF (18,108,109), BAY (40,81,106), LOM (37,40,81,87,108,109,(111)(112)(113), NOR (18,29,87,108,109,111), SPA (37,87,108,109,112,114), OFL (37,39,45,87,108,109,111), CIP (37,40,87,108,109,(111)(112)(113), LEV…”

“…Cleavage : Almost all FQs have been reported to induce SSB on plasmid DNA: ENO (18,37,52,87,108–111), PEF (18,108,109), BAY (40,81,106), LOM (37,40,81,87,108,109,111–113), NOR (18,29,87,108,109,111), SPA (37,87,108,109,112,114), OFL (37,39,45,87,108,109,111), CIP (37,40,87,108,109,111–113), LEV (45,112), RUF (70,108,109), FLE (108,109,111), TOS (87,111), ORB, CLI (108,109), MOX (40,45) and GAT (87). As observed for the other FQs DNA targets, most of 6,8 dihalogenated FQs (LOM, FLE, ORB, BAY and SPA) show a higher potential as DNA cleaving agents; also in this case methoxy substitution (MOX) tends to reduce this effect (40,45).…”

Photosensitized DNA Damage: The Case of Fluoroquinolones†

“…Numerous FQs have been reported to induce SSB on plasmid DNA (7,11,14,16–32); the results are shown in Table 2. As a general trend, FQs with a fluorine at C‐8 (LOM, FLE, ORB, BAY and SPA) show a higher potential as DNA cleaving agents, while methoxy substitution (MOX) tends to reduce this effect.…”

Photodegradation of Moxifloxacin in Aqueous and Organic Solvents: A Kinetic Study

“…Fluoroquinol ones are invol ved i n the photosensitized degradation of DNA (10) and also exhibit cellular phototoxicity (11). They are sensitive to light (10,(12)(13)(14)(15), and several studies have been carried out on the p h o t o d e g r a d a t i o n o f M F ( 1 1 , 1 6 -1 9 ) a n d o t h e r fluoroquinolones (18,(20)(21)(22)(23)(24)(25)(26)(27)(28). The photodegradation of quinolones (12) and fluoroquinolones in aqueous solution (17)(18)(19)24,28), follows first-order kinetics.…”