大环单端孢霉素作为抗真菌和抗肿瘤的化合物

Title:Macrocyclic trichothecenes as antifungal and anticancer compounds

Volume: 23 Issue: 1

Author(s): Maira Peres de Carvalho, Herbert Weich and Wolf-Rainer Abraham

Affiliation:

关键词: 倍半萜，大环单端孢霉素，细胞毒性，抗肿瘤活性，杆孢菌素，作用方式，构效关系。

摘要: Trichothecenes are sesquiterpenoid metabolites produced by fungi and species of the plant genus Baccharis, family Asteraceae. They comprise a tricyclic core with an epoxide at C-12 and C-13 and can be grouped into non-macrocyclic and macrocyclic compounds. While many of these compounds are of concern in agriculture, the macrocyclic metabolites have been evaluated as antiviral, anti-cancer, antimalarial and antifungal compounds. Some known cytotoxic responses on eukaryotic cells include inhibition of protein, DNA and RNA syntheses, interference with mitochondrial function, effects on cell division and membranes. These targets however have been elucidated essentially employing non-macrocyclic trichothecenes and only one or two closely related macrocyclic compounds. For several macrocyclic trichothecenes high selectivity against fungal species and against cancer cell lines have been reported suggesting that the macrocycle and its stereochemistry are of crucial importance regarding biological activity and selectivity. This review is focused on compounds belonging to the macrocyclic type, where a cyclic diester or triester ring binds to the trichothecane moiety at C-4 and C- 15 leading to natural products belonging to the groups of satratoxins, verrucarins, roridins, myrotoxins and baccharinoids. Their biological activities, cytotoxic mechanisms and structure-activity relationships (SAR) are discussed. From the reported data it becomes evident that even small changes in the molecules can lead to pronounced effects on biological activity or selectivity against cancer cells lines. Understanding the underlying mechanisms may help to design highly specific drugs for cancer therapy.

Cite this article as:

Maira Peres de Carvalho, Herbert Weich and Wolf-Rainer Abraham , Macrocyclic trichothecenes as antifungal and anticancer compounds, Current Medicinal Chemistry 2016; 23 (1) . https://dx.doi.org/10.2174/0929867323666151117121521