Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase
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 s...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2018/9242616 |
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| author | Fabio Arias M. Encarnación Camacho M. Dora Carrión Meriem Chayah Miguel Romero Juan Duarte Miguel A. Gallo |
| author_facet | Fabio Arias M. Encarnación Camacho M. Dora Carrión Meriem Chayah Miguel Romero Juan Duarte Miguel A. Gallo |
| author_sort | Fabio Arias |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-59a3c0e1dfad444fb3f3f0b639b7a771 |
| institution | Kabale University |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-59a3c0e1dfad444fb3f3f0b639b7a7712025-02-03T05:58:14ZengWileyJournal of Chemistry2090-90632090-90712018-01-01201810.1155/2018/92426169242616Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide SynthaseFabio Arias0M. Encarnación Camacho1M. Dora Carrión2Meriem Chayah3Miguel Romero4Juan Duarte5Miguel A. Gallo6Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, s/n, 18071 Granada, SpainDepartamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, s/n, 18071 Granada, SpainDepartamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, s/n, 18071 Granada, SpainDepartamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, s/n, 18071 Granada, SpainDepartamento de Farmacología, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, s/n, 18071 Granada, SpainDepartamento de Farmacología, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, s/n, 18071 Granada, SpainDepartamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, s/n, 18071 Granada, SpainTwo 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.http://dx.doi.org/10.1155/2018/9242616 |
| spellingShingle | Fabio Arias M. Encarnación Camacho M. Dora Carrión Meriem Chayah Miguel Romero Juan Duarte Miguel A. Gallo Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase Journal of Chemistry |
| title | Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase |
| title_full | Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase |
| title_fullStr | Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase |
| title_full_unstemmed | Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase |
| title_short | Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase |
| title_sort | thiadiazoline and pyrazoline based carboxamides and carbothioamides synthesis and inhibition against nitric oxide synthase |
| url | http://dx.doi.org/10.1155/2018/9242616 |
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