title: Efficient synthesis of novel 3-aryl-5-(4-chloro-2-morpholinothiazol-5-yl)-4,5-dihydro-1H-pyrazoles and their antifungal activity alone and in combination with commercial antifungal agents.
abstract: The α,β-unsaturated carbonyl compounds 5a-f were prepared by reaction between 2-chloro-4-morpholinothiazol-5-carbaldehyde 3 and substituted acetophenones 4a-f. Treatment of compounds 5a-f with hydrazine hydrate employing mild reaction conditions led to the formation of 4,5-dihydro-1H-pyrazoles 6a-f. Then the treatment with acetic anhydride or formic acid afforded the expected 4,5-dihydro-1H-pyrazoles 7a-f and 8a-f. The antifungal activity of each series of synthesized compounds was determined against the clinically important fungi Candida albicans and Cryptococcus neoformans. In addition, the most active compounds 7e and 7f were tested in combination with the commercial antifungal agents: fluconazole, itraconazole, and amphotericin B. Compound 7e showed a synergistic effect with fluconazole against C. albicans while 7f showed synergistic activities with all tested antifungal drugs against the same yeast.
authors.affiliation: Heterocyclic Compounds Research Group, Department of Chemistry, Universidad del Valle, Cali, Colombia.
authors.forename: Juan
authors.initials: J
authors.lastname: Ramírez
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Rodríguez
authors.forename: Jairo
authors.initials: J
authors.lastname: Quiroga
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Abonia
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Sortino
authors.forename: Susana A
authors.initials: SA
authors.lastname: Zacchino
authors.forename: Braulio
authors.initials: B
authors.lastname: Insuasty
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000254:growth & development; D004357:Drug Synergism; D057166:High-Throughput Screening Assays; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D011720:Pyrazoles; D013844:Thiazoles
keywords: 2-Chloro-4-morpholinothiazol-5-carbaldehyde; 4,5-Dihydro-1H-pyrazoles; Antifungal activity; Commercial antifungal agents; Synergistic effect