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Journal of Chemistry
Volume 2018, Article ID 9242616, 15 pages
https://doi.org/10.1155/2018/9242616
Research Article

Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase

1Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, s/n, 18071 Granada, Spain
2Departamento de Farmacología, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, s/n, 18071 Granada, Spain
3CIBERCV, Granada, Spain

Correspondence should be addressed to M. Encarnación Camacho; se.rgu@ohcamace and M. Dora Carrión; se.rgu@noirracd

Received 13 November 2017; Revised 18 December 2017; Accepted 11 January 2018; Published 20 March 2018

Academic Editor: Fabio Polticelli

Copyright © 2018 Fabio Arias et al. 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.

Abstract

Two new families of pyrazoline and thiadiazoline heterocycles have been developed. Their inhibitory activities against two different isoforms of nitric oxide synthase (inducible and neuronal NOS) are reported. The novel derivatives were synthesized combining the arylthiadiazoline or arylpyrazoline skeleton and a carboxamide or carbothioamide moiety, used as starting material ethyl 2-nitrobenzoates or substituted nitrobenzaldehydes, respectively. The structure-activity relationships of final molecules are discussed in terms of the R1 radical effects in the aromatic ring, the Y atom in the heterocyclic system, the X heteroatom in the main chain, and the R2 substituent in the carboxamide or carbothioamide rest. In general, thiadiazolines (5a–e) inhibit preferentially the neuronal isoform; among them, 5a is the best nNOS inhibitor (74.11% at 1 mM, IC50 = 420 μM). In contrast, pyrazolines (6a–r) behave better as iNOS than nNOS inhibitors, 6m being the best molecule of this series (76.86% at 1 mM of iNOS inhibition, IC50 = 130 μM) and the most potent of all tested compounds.