Synthesis, characterization, POM analysis and antifungal activity of novel heterocyclic chalcone derivatives containing acylated pyrazole

Abstract

A series of heterocyclic chalcone derivatives (4a–h) were synthesized and characterized by IR, 1H and 13C NMR as well as MS. All the synthesized compounds were evaluated for their antifungal activity on Candida albicans and Aspergillus niger. The assay revealed that compounds 3d and 4f showed significant activity against both tested fungal strains. POM analyses showed that the compounds are highly lipophyllic but present a potential bioactivity. Moreover, they have no NH–O or N–HO intramoleculcular interaction which is a crucial parameter controlling solubility of compounds possessing these encouraging pharmaceutical properties. This series gives us an important lesson in drug design: We should take the balance of hydrosolubility/lipophilicity into consideration. POM analyses were in agreement with the idea of coexistence of two combined antifungal N,O and O,S-pharmacophore sites for series 4a–h. On the other hand, two coexistents and identical N,Cl-pharmacophore sites have been identified for Fluconazole.