This review provides readers with an overview of the main synthetic methodologies for 1,3,4-oxadiazole derivatives, and of their broad spectrum of pharmacological activities as reported over the past twelve years.

Abstract:Five new 1-(2-(5-nitrofuran-2-yl)-5-(aryl)-1,3,4-oxadiazol-3-(2H)-yl) ethanone compounds 5a-e were synthesized by cyclization of N-acylhydrazones 4a-e with acetic anhydride under reflux conditions. Their structures were fully characterized by IR, 1 H-NMR, and 13 C-NMR. Furthermore, evaluations of the antibacterial activity of the 1,3,4-oxadiazoles 5a-e and N-acylhydrazones 4a-e showed strong activity against several strains of Staphylococcus aureus, with MICs between 4 μg/mL to 32 μg/mL. In silico studies of the parameters of Lipinski's Rule of Five, as well as the topological polar surface area (TPSA), absorption percentage (% ABS), drug likeness and drug score indicate that these compounds, especially 4a and 5d, have potential to be new drug candidates.

The first hyperpolarizabilities of the mesoionic compounds (MICs) 2-(4-chlorophenyl)-3-methyl-4-phenyl-1,3-thiazolium-5-thiolate (MIC-1), 2-(4-chlorophenyl)-3-methyl-4-(4-methylphenyl)-1,3-thiazolium-5-thiolate (MIC-2), and (2-(4-chlorophenyl)-3-methyl-4-(4-methoxyphenyl)-1,3-thiazolium-5-thiolate) (MIC-3), dissolved in dimethyl sulfoxide (DMSO), are reported here for the first time to our knowledge. Hyper-Rayleigh scattering experiments were performed with an excitation source operating at λ = 1180 nm (ω = 8475 cm–1). The measured hyperpolarizability, β­(2ω), was used to calculate the static hyperpolarizability, β(0), by applying the classical two-level model. The values obtained for β(0) were 10.1 × 10–30 esu (MIC-1), 8.7 × 10–30 esu (MIC-2), and 10.4 × 10–30 esu (MIC-3) which are smaller than previous theoretical predictions that did not consider features related to the liquid phase.

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Natural products have an important role as prototypes in the synthesis of new anticancer drugs. Piperine is an alkaloid amide with antitumor activity and significant toxicity. Then, the N-(p-nitrophenyl)acetamide piperinoate (HE-02) was synthesized, and tested for toxicological and antitumor effects. The toxicity was evaluated in vitro (on RAW 264.7 cells and mice erythrocytes) and in vivo (acute toxicity in mice). The Ehrlich ascites carcinoma model was used to evaluate the antitumor activity of HE-02 (6.25, 12.5 or 25 mg/kg, intraperitoneally, i.p.), as well as toxicity. HE-02 induced only 5.01% of hemolysis, and reduced the viability of RAW 264.7 cells by 49.75% at 1000 µg/mL. LD50 (lethal dose 50%) was estimated at around 2000 mg/kg (i.p.). HE-02 reduced Ehrlich tumor cell viability and peritumoral microvessels density. There was an increase of Th1 helper T lymphocytes cytokine profile levels (IL-1β, TNF-α, IL-12) and a decrease of Th2 cytokine profile (IL-4, IL-10). Moreover, an increase was observed on reactive oxygen species and nitric oxide production. Weak in vivo toxicological effects were recorded. Our data provide evidence that the piperine analogue HE-02 present low toxicity, and its antitumor effect involves modulation of immune system to a cytotoxic Th1 profile.