Natural Product-Based Phenols as Novel Probes for Mycobacterial and Fungal Carbonic Anhydrases
Rohan A Davis, Andreas Hofmann, Asiah Osman, Rebecca A Hall, Fritz A Muehlschlegel, Daniela Vullo, Alessio Innocenti, Claudiu T Supuran, Sally-Ann Poulsen
Journal of Medicinal Chemistry | AMER CHEMICAL SOC | Published : 2011
In order to discover novel probes that may help in the investigation and control of infectious diseases through a new mechanism of action, we have evaluated a library of phenol-based natural products (NPs) for enzyme inhibition against four recently characterized pathogen β-family carbonic anhydrases (CAs). These include CAs from Mycobacterium tuberculosis, Candida albicans, and Cryptococcus neoformans as well as α-family human CA I and CA II for comparison. Many of the NPs selectively inhibited the mycobacterial and fungal β-CAs, with the two best performing compounds displaying submicromolar inhibition with a preference for fungal over human CA inhibition of more than 2 orders of magnitude..View full abstract
Awarded by Australian Research Council
Awarded by Medical Research Council
This research was financed in part by the Australian Research Council (Grant DP0877554 to S.-A.P.), a grant of the 6th Framework Programme (FP) of the European Union (DeZnIT Project), and a grant of the 7th FP of EU (Metoxia Project). The support of this study by a Program Grant from the Australian Synchrotron to A. H. is gratefully acknowledged.