Pyrazolines are five-membered heterocycles possessing two adjacent nitrogens. They have attracted significant attention from organic and medicinal chemists due to their potent biological activities and the numerous possibilities for structural diversification. In the last decade, they have been intensively studied as targets for potential anticancer therapeutics, producing a steady yearly rise in the number of published research articles. Many pyrazoline derivatives have shown remarkable cytotoxic activities in the form of heterocyclic or non-heterocyclic based hybrids, such as with coumarins, triazoles, and steroids. The enormous amount of related literature in the last 5 years prompted us to collect all these published data from screening against cancer cell lines, or protein targets like EGFR and structure activity relationship studies. Therefore, in the present review, a comprehensive account of the compounds containing the pyrazoline nucleus will be provided. The chemical groups and the structural modifications responsible for the activity will be highlighted. Moreover, emphasis will be given on recent examples from the literature and on the work of research groups that have played a key role in the development of this field.

Photodynamic therapy (PDT) is a minimally invasive approach to treat various forms of cancer, based on the ability of certain non-toxic molecules (photosensitizers) to generate reactive oxygen species (ROS) after excitation by light of a certain wavelength and eventually induce strong phototoxic reactions against malignant cells and other pathogens. Curcumin is one of the most extensively investigated phytochemicals with a wide range of therapeutic properties and has been shown to induce strong photocytotoxic effects in micromolar concentrations against a variety of cancer cell lines. Curcumin (1) is comparatively evaluated with the naturally occurring bisdemethoxy Curcumin (2), which lacks the two methoxy groups, as well as two newly synthesized curcuminoids, the cinnamaldehyde derivative (3) and the dimethylamino one (4), designed to increase the absorption maximum and hence the tissue penetration. The synthetic curcuminoids were successfully synthesized in sufficient amounts and their photophysical properties such as absorption, fluorescence, photobleaching and free radical generation were investigated. Compound 4 exhibited a significant increase in peak absorption (497 nm) and strong fluorescent emission signals were recorded for all curcuminoids. Photobleaching of 4 was comparable to 1 whereas 2 and 3 showed more extended photobleaching but much higher ROS production in very short irradiation times. Compounds 2 and 4 exhibited specific intracellular localization. After dark and light cytotoxicity experiments against LNCaP prostate cancer cell line for all curcuminoids, concentration of 3 μM and irradiance of 6 mW cm⁻² were selected for the PDT application which resulted in remarkable results with very short LD₅₀. Curcuminoids 2 and 4 exhibited a significant dose-dependent PDT effect. The biphasic dose–response photodynamic effect observed for 1 and 3 may provide a strategy against prolonged and sustained photosensitivity.

There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work, we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or hemolytic properties at similar concentrations. The structures of 21 metal complexes that display high antifungal activity (MIC ≤1.25 μM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been previously tested for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larva model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex Pt1 significantly reduces fungal load in an in vivo G. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.

The successful synthesis of hydroxyapatite (HA), β-Tricalcium phosphate (β-TCP) and two biphasic mixtures (BCPs) of the two was performed by means of wet precipitation. The resulting crystals were characterized and the BCP composition was analyzed and identified as 13% HA—87% TCP and 41% HA—59% TCP. All samples were treated with curcumin solutions, and the degree of curcumin loading and release was found to be proportional to the TCP content of the ceramic. No further cytotoxicity was observed upon MG-63 treatment with the curcumin-loaded ceramics. Finally, the alkaline phosphatase activity of the cells was found to increase with increasing content of TCP, which provides an encouraging proof of concept for the use of curcumin-loaded synthetic biomaterials in bone remodeling.

Alzheimer’s disease (AD) is a multifactorial disorder strongly involving the formation of amyloid-β (Aβ) oligomers, which subsequently aggregate into the disease characteristic insoluble amyloid plaques, in addition to oxidative stress, inflammation and increased acetylcholinesterase activity. Moreover, Aβ oligomers interfere with the expression and activity of Glycogen synthase kinase-3 (GSK3) and Protein kinase B (PKB), also known as AKT. In the present study, the potential multimodal effect of two synthetic isatin thiosemicarbazones (ITSCs), which have been previously shown to prevent Aβ aggregation was evaluated. Both compounds resulted in fully reversing the Aβ-mediated toxicity in SK-NS-H cells treated with exogenous Aβ peptides at various pre-incubation time points and at 1 μM. Cell survival was not recovered when compounds were applied after Aβ cell treatment. The ITSCs were non-toxic against wild type and 5xFAD primary hippocampal cells. They reversed the inhibition of Akt and GSK-3β phosphorylation in 5xFAD cells. Finally, they exhibited good antioxidant potential and moderate lipoxygenase and acetylcholinesterase inhibition activity. Overall, these results suggest that isatin thiosemicarbazone is a suitable scaffold for the development of multimodal anti-AD agents.