Naturally occurring aristolochic acid analogues and their toxicities

Aristolochic acids are known for causing aristolochic acid nephropathy, a renal fibrosis often associated with urothelial carcinoma. Aristolochic acid I and II are considered to be the cause of these nephrotoxic and carcinogenic effects. However a variety of aristolochic acid analogues, including aristolactams and 4,5-dioxoaporphines have been reported. Their implications in aristolochic acid nephropathy have possibly been overlooked. In this report, in vivo and in vitro toxicity and mutagenicity of these three classes of compounds are discussed. Furthermore, the review gives an update of aristolochic acids, aristolactams and 4,5-dioxoaporphines reported between 2003 and 2013 and their biological activities.