Synthesis and antifungal activity of substituted salicylaldehyde hydrazones, hydrazides and sulfohydrazides

• Published in: Bioorganic & medicinal chemistry Vol. 22; no. 17; pp. 4629 - 4636
• Main Authors: Backes, Gregory L., Neumann, Donna M., Jursic, Branko S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2014
• Subjects: Aldehydes - chemical synthesis; Aldehydes - chemistry; Aldehydes - pharmacology; Animals; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antifungals; Candida - drug effects; Cell Line; Cercopithecus aethiops; Dose-Response Relationship, Drug; Hep G2 Cells; Humans; Hydrazides; Hydrazines - chemical synthesis; Hydrazines - chemistry; Hydrazines - pharmacology; Hydrazones; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Microbial Sensitivity Tests; Molecular Structure; Salicylaldehyde; Structure-Activity Relationship; Vero Cells; Antifungals; Hydrazones; Hydrazides; Salicylaldehyde
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2014.07.022

Efficient synthetic procedures for the preparation of acid hydrazines and hydrazides were developed by converting the corresponding carboxylic acid into the methyl ester catalyzed by Amberlyst-15, followed by a reaction with hydrazine monohydrate. Sulfohydrazides were prepared from the corresponding sulfonyl chlorides and hydrazine monohydrate. Both of these group of compounds were condensed with substituted salicylaldehydes using gradient concentration methods that generated a large library of hydrazone, hydrazide and sulfohydrazide analogs. Antifungal activity of the prepared analogs showed that salicylaldehyde hydrazones and hydrazides are potent inhibitors of fungal growth with little to no mammalian cell toxicity, making these analogs promising new targets for future therapeutic development.