title: A prodrug approach to improve the physico-chemical properties and decrease the genotoxicity of nitro compounds.
abstract: In therapeutics research, the nitro compounds are part of an important group of drugs with multiple pharmacological activities. However, in drug design, the inclusion of a nitro group in a molecule changes the physico-chemical and electronic properties and is associated with increased mutagenicity and carcinogenicity. In addition, several studies have related the relationship between the antimicrobial and/or anti-protozoal activity and the mutagenic effect to reduction of the nitro group. This work reviews the toxicity of nitro compounds and shows how the use of prodrugs can increase the biological activity and decrease the genotoxicity of nitro compounds, without any modification in nitro reduction behavior, but rather by physico-chemical improvement. Examples are given of metronidazole and nitrofurazone prodrugs.
authors.affiliation: Lapdesf- Laboratory of Drug Desing, Dept of Drugs and Medicines, School of Pharmaceutical Sciences, University of São Paulo State, Rodovia Araraquara- Jaú km1, cep 14802-901, Araraquara, SP, Brazil. chungmc@fcfar.unesp.br
authors.forename: Man Chin
authors.initials: MC
authors.lastname: Chung
authors.forename: Priscila Longhin
authors.initials: PL
authors.lastname: Bosquesi
authors.forename: Jean Leandro
authors.initials: JL
authors.lastname: dos Santos
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D055598:Chemical Phenomena; D004249:DNA Damage; D015195:Drug Design; D006801:Humans; D008795:Metronidazole / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D015394:Molecular Structure; D009574:Nitro Compounds / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D009583:Nitrofurazone / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D009574:Nitro Compounds; D011355:Prodrugs; D008795:Metronidazole; D009583:Nitrofurazone