Ferrocene-containing tetrahydropyrazolopyrazolones: Antioxidant and antimicrobial activity.

Abstract 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(5 H)-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-ferrocenoyl-5-mesityltetrahydropyrazolo[1,2- a ]pyrazol-1(5 H)-one (5e) and 6-ferrocenoyl-5-(2-methoxyphenyl)tetrahydropyrazolo[1,2- a ]pyrazol-1(5 H)-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(5 H)-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(5 H)-ones 5b , 5c , 5d , 5j as well as cis - 6 - ferrocenoyl - 5 - (p - tolyl)tetrahydropyrazolo[1,2- a ]pyrazol-1(5 H) - 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(5 H)-one (6l) and cis -6-ferrocenoyl-5-(naphthalen-2-yl)tetrahydropyrazolo[1,2- a ]pyrazol-1(5 H)-one (6n) have potential to become lead molecules in drug discovery process. Graphical abstract A series of new ferrocenes (5‑aryl‑6‑ferrocenoyltetrahydropyrazolo[1,2‑ a ]pyrazol‑1(5 H)-ones) is characterized in a terms of examination of their biological activities. Synthesized compounds exhibited excellent antioxidant properties, and in some cases antibacterial and antifungal activity. Unlabelled Image Highlights • A series of new ferrocenes is synthesized using easy performable procedure. • The isolated pure ferrocenes showed pronounced antioxidant activity. • The tested compounds exhibited different and selective antimicrobial activity. [ABSTRACT FROM AUTHOR]