The first activation studies of the η-carbonic anhydrase from the malaria parasite Plasmodium falciparum with amines and amino acids

Andrea Angeli; Sonia Del Prete; Fatmah A S Alasmary; Linah S Alqahtani; Zeid AlOthman; William A Donald; Clemente Capasso; Claudiu T Supuran

doi:10.1016/j.bioorg.2018.06.002

The first activation studies of the η-carbonic anhydrase from the malaria parasite Plasmodium falciparum with amines and amino acids

Bioorg Chem. 2018 Oct:80:94-98. doi: 10.1016/j.bioorg.2018.06.002. Epub 2018 Jun 4.

Authors

Andrea Angeli¹, Sonia Del Prete², Fatmah A S Alasmary³, Linah S Alqahtani⁴, Zeid AlOthman³, William A Donald⁵, Clemente Capasso⁶, Claudiu T Supuran⁷

Affiliations

¹ Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
² Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.
³ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁴ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; Department of Chemistry, King Faisal University, Alahsa, Saudi Arabia.
⁵ School of Chemistry, University of New South Wales, Sydney, New South Wales 2052, Australia.
⁶ Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy. Electronic address: clemente.capasso@ibbr.cnr.it.
⁷ Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy; Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; School of Chemistry, University of New South Wales, Sydney, New South Wales 2052, Australia. Electronic address: claudiu.supuran@unifi.it.

PMID: 29894892
DOI: 10.1016/j.bioorg.2018.06.002

Abstract

The first activation study of a η-class carbonic anhydrase (CAs, EC 4.2.1.1) is reported. A panel of 24 natural and non-natural amino acids and amines was used to explore the activation profile of Plasmodium falciparum CA (PfACA). The most effective activators belonged to the amino acid chemotype, with d-Glu, l-Asp, l-/d-Phe and l-/d-DOPA possessing activation constant in the range of 82 nM-0.75 µM, whereas l-/d-His, l-Tyr, 4-amino-l-Phe and l-Gln were slightly less effective (K_A in the range of 1.00-2.51 µM. The only amine with submicromolar activating properties was 1-(2-aminoethyl-piperazine) with a K_A of 0.71 µM, whereas histamine, dopamine and serotonin showed K_A ranging between 7.18 and 9.97 µM. As CA activators have scarcely been investigated for their interaction with protozoan CAs, this study may be relevant for an improved understanding of the role of this enzyme in the life cycle of the malaria producing organisms belonging to the genus Plasmodium.

Keywords: Activators; Carbonic anhydrase; Metalloenzymes; Plasmodium falciparum; Protozoa.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amines / chemistry
Amines / metabolism*
Amino Acids / chemistry
Amino Acids / metabolism*
Carbonic Anhydrases / chemistry
Carbonic Anhydrases / metabolism*
Humans
Isoenzymes / chemistry
Isoenzymes / metabolism
Kinetics
Life Cycle Stages
Plasmodium falciparum / enzymology*
Protozoan Proteins / chemistry
Protozoan Proteins / metabolism*
Structure-Activity Relationship

Substances

Amines
Amino Acids
Isoenzymes
Protozoan Proteins
Carbonic Anhydrases