Ferrocene-containing tetrahydropyrazolopyrazolones: Antioxidant and antimicrobial activity

A series of ferrocenes which contain dinitrogen-fused pyrazolidinone ring were synthesized from acryloylferrocene (4) and N,N'-cyclic azomethine imines (3). Novel 5-aryl-6-ferrocenoyltetrahydropyrazolo[1,2-a] pyrazol-1(5H)-ones were obtained as mixtures of two diastereoisomers (trans and cis) which were separated and isolated as pure substances. Ortho-substituted N,N'-cyclic azomethine imines 5-oxo-2-(2,4,6-trimethylbenzylidene)pyrazolidin-2-ium-1-ide (3e) and 2-(2-methoxybenzylidene)-5-oxopyrazolidin-2-ium-1-ide (3f) reacted stereoselectively affording only trans-6-ferrocenoy1-5-mesityltetrahydropyrazolo[1,2-a]pyrazol-1(5H)-one (5e) and 6-ferrocenoy1-5-(2-methoxyphenyl)tetrahydropyrazolo[1,2-a]pyrazol-1(5H)-one (5f). Ferrocenyl derivatives were screened for in vitro antioxidant and antifungal activities and excellent DPPH and ABTS radicals scavenging activity was observed with majority of tested 5-aryl-6-ferrocenoyltetrahydropyrazolo[1,2-a] pyrazol-1(511)-ones. Several tested compounds showed selective scavenging properties neutralizing ABTS' radical cations in contrast to inactivity toward DPPH . radicals. Trans-5-aryl-6-ferrocenoyltetrahydropyrazolo [1,2-a]pyrazol-1(514)-ones 5b, 5c, 5d, 5j as well as cis-6-ferrocenoy1-5-(p-tolyfltetrahydropyrazolo[1,2-a]pyrazol-1(511)-one (6d) displayed fungal growth inhibition at low concentration against C. albicans and/or A. brasiliensis. Molecular docking studies revealed that the cis-6-ferrocenoyl-5-(4-nitrophenyl)tetrahydropyrazolo [1,2-a] pyrazol-1(5H)-one (61) and cis-6-ferrocenoy1-5-(naphthalen-2-yl)tetrahydropyrazolo [1,2-a]pyra zol-1(5H-one (6n) have potential to become lead molecules in drug discovery process.