Innocenti, Alessio, Hall, Rebecca A., Schlicker, Christine, Mühlschlegel, Fritz A., Supuran, Claudiu T. (2009) Carbonic anhydrase inhibitors. Inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with aliphatic and aromatic carboxylates. Bioorganic & Medicinal Chemistry, 17 (7). pp. 2654-2657. ISSN 0968-0896. (doi:10.1016/j.bmc.2009.02.058) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:91845)
The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. | |
Official URL: https://doi.org/10.1016/j.bmc.2009.02.058 |
Abstract
The inhibition of the beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (Nce103) with carboxylates such as the C1-C5 aliphatic carboxylates, oxalate, malonate, maleate, malate, pyruvate, lactate, citrate and some benzoates has been investigated. The best Can2 inhibitors were acetate and maleate (K(I)s of 7.3-8.7 microM), whereas formate, acetate, valerate, oxalate, maleate, citrate and 2,3,5,6-tetrafluorobenzoate showed less effective inhibition, with K(I)s in the range of 42.8-88.6 microM. Propionate, butyrate, malonate, L-malate, pyruvate, L-lactate and benzoate, were weak Can2 inhibitors, with inhibition constants in the range of 225-1267 microM. Nce103 was more susceptible to inhibition with carboxylates compared to Can2, with the best inhibitors (maleate, benzoate, butyrate and malonate) showing K(I)s in the range of 8.6-26.9 microM. L-Malate and pyruvate together with valerate were the less efficient Nce103 inhibitors (K(I)s of 87.7-94.0 microM), while the remaining carboxylates showed a compact behavior of efficient inhibitors (K(I)s in the range of 35.1-61.6 microM). Notably the inhibition profiles of the two fungal beta-CAs was very different from that of the ubiquitous host enzyme hCA II (belonging to the alpha-CA family), with maleate showing selectivity ratios of 113.6 and 115 for Can2 and Nce103, respectively, over hCA II inhibition. Therefore, maleate is a promising starting lead molecule for the development of better, low nanomolar, selective beta-CA inhibitors.
Item Type: | Article |
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DOI/Identification number: | 10.1016/j.bmc.2009.02.058 |
Divisions: | Divisions > Division of Natural Sciences > Biosciences |
Depositing User: | Becky Hall |
Date Deposited: | 01 Dec 2021 09:36 UTC |
Last Modified: | 01 Dec 2021 17:23 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/91845 (The current URI for this page, for reference purposes) |
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