Phaeodactylum tricornutum as a model organism for testing the membrane penetrability of sulphonamide carbonic anhydrase inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry

Sonia Del Prete¹  Clemente Capasso¹  Vincenzo Carginale¹  Alessandra Rogato²  Claudiu T. Supuran³  Alessio Nocentini³ 

[1] Institute of Bioscience and BioResources, CNR, Naples, Italy;Institute of Bioscience and BioResources, CNR, Naples, Italy;Department of Integrative Marine Ecology, Stazione Zoologica Anton Dohrn, Naples, Italy;Neurofarba Department, University of Florence, Polo Scientifico, Sesto Fiorentino, Florence, Ital;

关键词: Carbonic anhydrase;    metalloenzymes;    sulphonamide inhibitors;    marine diatom;    membrane penetrability;   

DOI  :  10.1080/14756366.2018.1559840

来源: publisher

【 摘 要 】

Carbonic anhydrases (CAs) are ubiquitous metalloenzymes, which started to be investigated in detail in pathogenic, as well as non-pathogenic species since their pivotal role is to accelerate the physiological CO2 hydration/dehydration reaction significantly. Here, we propose the marine unicellular diatom Phaeodactylum tricornutum as a model organism for testing the membrane penetrability of CA inhibitors (CAIs). Seven inhibitors belonging to the sulphonamide type and possessing a diverse scaffold have been explored for their in vitro inhibition of the whole diatom CAs and the in vivo inhibitory effect on the growth of P. tricornutum. Interesting, inhibition of growth was observed, in vivo, demonstrating that this diatom is a good model for testing the cell wall penetrability of this class of pharmacological agents. Considering that many pathogens are difficult and dangerous to grow in the laboratory, the growth inhibition of P. tricornutum with different such CAIs may be subsequently used to design inhibition studies of CAs from pathogenic organisms.

【 授权许可】

CC BY