In recent years, spiro compounds have attracted significant interest in medicinal chemistry due to their numerous biological activities attributed primarily to their versatility and structural similarity to important pharmacophore centers. Currently, the development of drugs with potential antioxidant activities is of great importance since numerous investigations have shown that oxidative stress is involved in the development and progression of numerous diseases such as cancer, senile cataracts, kidney failure, diabetes, high blood pressure, cirrhosis, and neurodegenerative diseases, among others. This article provides an overview of the synthesis and various antioxidant activities found in naturally occurring and synthetic spiro compounds. Among the antioxidant activities reviewed are DPPH, ABTS, FRAP, anti-LPO, superoxide, xanthine oxidase, peroxide, hydroxyl, and nitric oxide tests, among others. Molecules that presented best results for these tests were spiro compounds G14, C12, D41, C18, C15, D5, D11, E1, and C14. In general, most active compounds are characterized for having at least one oxygen atom; an important number of them (around 35%) are phenolic compounds, and in molecules where this functional group was absent, aryl ethers and nitrogen-containing functional groups such as amine and amides could be found. Recent advances in the antioxidant activity profiles of spiro compounds have shown that they have a significant position in discovering drugs with potential antioxidant activities.

Pyrazolo[3,4- b ]pyridines derivatives have been synthesized via one-pot condensation of 3-methyl-1-phenyl-1 H -pyrazolo-5-amine ( 1 ), paraformaldehyde ( 2 ) and β-diketones ( 3 ) under microwave irradiation in aqueous media catalyzed by InCl ₃ .

This article describes the synthesis, characterization (¹H NMR, ¹³C NMR, FT-IR, HRMS and XRD), UV-Vis absorption and fluorescence spectra, theoretical analysis, evaluation of nonlinear optical properties (NLO), thermal analysis and determination of the hemolytic capacity of the compound (E)-N-(4-(3-(benzo[d][1,3]dioxol-5-yl)acryloyl)phenyl)quinoline-3-carboxamide (5). Radiological findings showed that compound 5 crystallized in space group Pca2₁. Furthermore, theoretical DFT studies performed with the B3LYP and M062X functionals showed good agreement with the experimental results and provided valuable information on the molecular and electronic structure, reactivity, polarizability, and kinematic stability of the compound. Besides, compound 5 did not show any hemolytic effect on human erythrocytes and exhibited strong NLO properties. The TG and DTA thermograms of quinoline–chalcone (5) revealed a multi-step thermal decomposition process with a total mass loss of 83.2%, including water content loss. The DTA curves exhibited endothermic peaks corresponding to decomposition steps, melting point, and thermochemical transition. Additionally, exothermic peaks in the DTA thermograms align with significant mass loss, confirming the compound's melting point and water content, as validated by X-ray diffraction analysis. These results contribute to the advancement of research on compounds with NLO properties and offer a promising avenue for the development of substances potentially applicable to optical devices in the biomedical field.

Pyrazole-fused phenanthroline compounds were obtained through several synthetic routes. NMR, HRMS, and IR techniques were used to characterize and confirm the chemical structures. Crystal structures were obtained from compounds 3a, 5b, 5j, 5k, and 5n and analyzed using X-ray diffraction. Compounds were evaluated as acetyl (AChE) and butyrylcholinesterase (BChE) inhibitors, and the results showed a moderate activity. Compound 5c presented the best activity against AChE (IC₅₀ = 53.29 μM) and compound 5l against BChE enzyme (IC₅₀ = 119.3 μM). Furthermore, the ability of the synthetic compounds to scavenge cationic radicals DPPH and ABTS was evaluated. Compound 5e (EC₅₀ = 26.71 μg mL⁻¹) presented the best results in the DPPH assay, and compounds 5e, 5f and 5g (EC₅₀ = 11.51, 3.10 and <3 μg mL⁻¹, respectively) showed better ABTS cationic radical scavenging results. Finally, in silico analyses indicated that 71% of the compounds show good oral availability and are within the ranges established by the Lipinski criteria.

A small series of tetrahydroindazoles was prepared, starting from 2-acetylcyclohexanone and different hydrazines using reflux and a focused microwave reactor. Microwave irradiation (MW) favored the formation of the desired products with improved yields and shortened reaction times. This is a simple and green method for the synthesis of substituted tetrahydroindazole derivatives. The in vitro antioxidant activity was evaluated using the DPPH and ABTS methods. In these assays, 2-(4-fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) showed moderate DPPH decoloring activity, while 3-methyl-4,5,6,7-tetrahydro-1H-indazole (3a), 3-methyl-2-phenyl-4,5,6,7-tetrahydro-2H-indazole (3b) and 2-(4-fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) were the most active in the ABTS assay. All compounds were well characterized by IR, ¹H-, ¹³C-NMR and GC-MS spectroscopy and physical data, while the structure of 4-(3-methyl-4,5,6,7-tetrahydro-2H-indazol-2-yl)benzoic acid (3e) was also determined by single crystal X-ray analysis.

A single crystal of a piperonal chalcone derivative was obtained, fully characterized, and crystallized by a slow evaporation technique. The synthesized compound was characterized by UV-Visible, FT-IR, HRMS, ¹H NMR, and ¹³C NMR spectroscopic studies and X-ray crystallography, revealing that the crystal belongs to a triclinic crystal system with a P space group, Z = 2. In the present work, we focus on molecular modeling studies such as Hirshfeld surface analysis, energy framework calculations, frontier molecular orbital analysis, natural bond orbital analysis, and NLO properties of a π-conjugate system combining the chalcone and the pyrazole[3,4-b]pyridine scaffolds to describe the in-depth structural analysis thereof. Good agreement was found between the calculated results and experimental data. In addition, Hirshfeld surface analysis of the crystal structure showed that the intermolecular stabilization in the crystal packing comes mainly from H⋯H bond interactions. The chalcone crystal exhibits significant NLO properties suggesting that it could be considered a potential candidate for application in nonlinear optical devices.