Azole antifungals, including fluconazole, have long been the first-line antifungal agents in the fight against fungal infections. The emergence of drug-resistant strains and the associated increase in mortality from systemic mycoses has prompted the development of new agents based on azoles. We reported a synthesis of novel monoterpene-containing azoles with high antifungal activity and low cytotoxicity. These hybrids demonstrated broad-spectrum activity against all tested fungal strains, with excellent minimum inhibitory concentration (MIC) values against both fluconazole-susceptible and fluconazole-resistant strains of Candida spp. Compounds 10a and 10c with cuminyl and pinenyl fragments demonstrated up to 100 times lower MICs than fluconazole against clinical isolates. The results indicated that the monoterpene-containing azoles had much lower MICs against fluconazole-resistant clinical isolates of Candida parapsilosis than their phenyl-containing counterpart. In addition, the compounds did not exhibit cytotoxicity at active concentrations in the MTT assay, indicating potential for further development as antifungal agents.

A novel series of 2-pyrazoline derivatives were designed, synthesized, and evaluated for cholinesterase (ChE) inhibitory, Aβ anti-aggregating and neuroprotective activities. Among these, 3d, 3e, 3g, and 3h were established as the most potent and selective BChE inhibitors (IC₅₀ = 0.5–3.9 μM), while 3f presented dual inhibitory activity against BChE and AChE (IC₅₀ = 6.0 and 6.5 μM, respectively). Kinetic analyses revealed that 3g is a partial noncompetitive inhibitor of BChE (Ki = 2.22 μM), while 3f exerts competitive inhibition on AChE (Ki = 0.63 μM). The active compounds were subsequently screened for further assessments. 3f, 3g and 3h reduced Aβ_1–42 aggregation levels significantly (72.6, 83.4 and 63.4%, respectively). In addition, 3f demonstrated outstanding neuroprotective effects against Aβ_1–42-induced and H₂O₂-induced cell toxicity (95.6 and 93.6%, respectively). Molecular docking studies were performed with 3g and 3f to investigate binding interactions inside the active sites of BChE and AChE. Compounds 3g and 3f might have the multifunctional potential for use against Alzheimer's disease.