Next Article in Journal
Substituent Effects in Multivalent Halogen Bonding Complexes: A Combined Theoretical and Crystallographic Study
Next Article in Special Issue
Exploring Alternative Radiolabeling Strategies for Sialic Acid-Binding Immunoglobulin-Like Lectin 9 Peptide: [68Ga]Ga- and [18F]AlF-NOTA-Siglec-9
Previous Article in Journal
The Major Chromophore Arising from Glucose Degradation and Oxidative Stress Occurrence during Lens Proteins Glycation Induced by Glucose
Previous Article in Special Issue
Three-Dimensional Analysis of the Interactions between hLDH5 and Its Inhibitors
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(1), 17; https://doi.org/10.3390/molecules23010017

Potent and Selective Carboxylic Acid Inhibitors of Tumor-Associated Carbonic Anhydrases IX and XII

1
Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, I-53100 Siena, Italy
2
Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino (Firenze), Italy
3
Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, viale Regina Elena 291, I-00161 Roma, Italy
4
Dipartimento NEUROFARBA, Sezione di Scienze Farmaceutiche, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy
5
Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, BioLife Science Building, Suite 333, 1900 N 12th Street, Philadelphia, PA 19122, USA
*
Author to whom correspondence should be addressed.
Received: 29 November 2017 / Revised: 19 December 2017 / Accepted: 20 December 2017 / Published: 22 December 2017
(This article belongs to the Special Issue Medicinal Chemistry in Europe)
Full-Text   |   PDF [3654 KB, uploaded 27 December 2017]   |  

Abstract

Selective inhibition of tumor-associated carbonic anhydrase (CA; EC 4.2.1.1) isoforms IX and XII is a crucial prerequisite to develop successful anticancer therapeutics. Herein, we confirmed the efficacy of the 3-nitrobenzoic acid substructure in the design of potent and selective carboxylic acid derivatives as CAs inhibitors. Compound 10 emerged as the most potent inhibitor of the tumor-associated hCA IX and XII (Ki = 16 and 82.1 nM, respectively) with a significant selectivity with respect to the wide spread hCA II. Other 3-nitrobenzoic acid derivatives showed a peculiar CA inhibition profile with a notable potency towards hCA IX. View Full-Text
Keywords: carbonic anhydrase inhibitors (CAIs); carboxylic acid; tumor-associated isoforms; isoform selectivity; molecular modeling carbonic anhydrase inhibitors (CAIs); carboxylic acid; tumor-associated isoforms; isoform selectivity; molecular modeling
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Cau, Y.; Vullo, D.; Mori, M.; Dreassi, E.; Supuran, C.T.; Botta, M. Potent and Selective Carboxylic Acid Inhibitors of Tumor-Associated Carbonic Anhydrases IX and XII. Molecules 2018, 23, 17.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top