Synthesis of substituted 3-aryl-4-hydroxycoumarins of expected antimicrobial activity in tenacibaculosis disease

Abstract

Bacterial diseases of freshwater fish epithelia have been extensively studied; however in marine fishes relatively few bacterial skin and gill diseases have been characterized. Tenacibaculum maritimum, a Gram-negative and filamentous bacterium, has been described as the etiological agent of tenacibaculosis in marine fish. Since 1990, as the farming of fish became a steadily growing industry, this disease has been widely distributed in several countries and is considered a limiting factor for the culture of many species of commercial value in the world. Among the drugs used in the past few years enrofloxacin proved to be the most useful compound in the control of tenacibaculosis outbreaks, although the rapid appearance of resistant strains has already been described. Therefore, it is important to discover new classes of selective antimicrobial drugs. Coumarin derivatives are a class of compounds that present a wide range of pharmacological activities. Among others, recent studies pay special attention to the antibiotic properties of the coumarin moiety. In order to contribute to the development of new agents, in the present communication we have synthesized new 3-arylcoumarin derivatives, structurally related with well know antibiotic novobiocin. On this scaffold we introduced substituents with different electronic, steric and/or lipophilic properties in different positions of the aromatic rings. The compounds have been prepared via a palladium-catalyzed coupling type Suzuki reaction of phenyliodonium zwitterion species previously synthesized by us. Further, were evaluated for antibacterial activity against bacterial and fungal strains. The preliminary results of biological activity and/or selectivity against Tenacibaculum Maritimum will be presented.