Tetrahydropyrazolopyrazolones: Synthesis, X-ray crystallography and antimicrobial activity

1,3-Dipolar cycloaddition is a valuable reaction for synthesizing heterocycles which form the core of pharmacophores with diverse bioactivities. In this study, structurally intriguing cis/trans pairs of 6-acyl-5-aryltetrahydropyrazolo[1,2-a]pyrazol-1(5H)-ones were synthesized via the 1,3-dipolar cycloaddition of N,N'-cyclic azomethine imines and vinyl-containing enones to assess their antimicrobial activity. The crystal structures of two cis and two trans tetrahydropyrazolopyrazolone derivatives were analyzed and their geometrical features were compared with structurally related compounds from the Cambridge Structural Database (CSD). The antimicrobial activity evaluation of the synthesized tetrahydropyrazolopyrazolones against bacteria and fungi revealed weak to moderate efficacy, with minimum inhibitory concentration (MIC) values ranging from 2 to 8 mM for most species. Notably, the compounds exhibited a stronger inhibitory effect on mold growth compared to Candida albicans. Furthermore, the tested compounds demonstrated greater efficacy against Gram-positive bacteria than Gram-negative bacteria.