1. Inhibition survey with phenolic compounds against the δ- and η-class carbonic anhydrases from the marine diatom thalassiosira weissflogii and protozoan Plasmodium falciparum .
- Author
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Alissa SA, Alghulikah HA, ALOthman ZA, Osman SM, Del Prete S, Capasso C, Nocentini A, and Supuran CT
- Subjects
- Antiprotozoal Agents chemical synthesis, Antiprotozoal Agents chemistry, Carbonic Anhydrase Inhibitors chemical synthesis, Carbonic Anhydrase Inhibitors chemistry, Dose-Response Relationship, Drug, Humans, Molecular Structure, Parasitic Sensitivity Tests, Phenols chemical synthesis, Phenols chemistry, Plasmodium falciparum enzymology, Structure-Activity Relationship, Antiprotozoal Agents pharmacology, Carbonic Anhydrase Inhibitors pharmacology, Carbonic Anhydrases metabolism, Diatoms enzymology, Phenols pharmacology, Plasmodium falciparum drug effects
- Abstract
The inhibition of δ- and η-class carbonic anhydrases (CAs; EC 4.2.1.1) was poorly investigated so far. Only one δ-CA, TweCA from the diatom Thalassiosira weissflogii, and one η-CA, PfCA, from Plasmodium falciparum , have been cloned and characterised to date. To enrich δ- and η-CAs inhibition profiles, a panel of 22 phenols was investigated for TweCA and PfCA inhibition. Some derivatives showed effective, sub-micromolar inhibition of TweCA (K
I s 0.81-65.4 µM) and PfCA (KI s 0.62-78.7 µM). A subset of compounds demonstrated a significant selectivity for the target CAs over the human physiologically relevant ones. This study promotes the identification of new potent and selective inhibitors of TweCA and PfCA , which could be considered as leads for finding molecular probes in the study of carbon fixation processes (in which TweCA and orthologue enzymes are involved) or drug candidates in the treatment of malaria.- Published
- 2020
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