1,2,4-Oxadiazoles have emerged as a significant class of heterocyclic compounds in medicinal chemistry due to their diverse biological activities and versatile applications in drug discovery. Herein is reported an in-depth analysis of the structural properties, synthetic methodologies, and pharmacological significance of 1,2,4-oxadiazoles. The compound's unique five-membered ring containing three heteroatoms offers remarkable stability and tunable physicochemical properties, making it an attractive scaffold for the development of novel therapeutic agents, as confirmed by already approved drugs. The review highlights the broad spectrum of biological activities associated with 1,2,4-oxadiazoles, including antimicrobial, anti-inflammatory, anticancer, antiviral, and central nervous system related activities. These diverse effects underscore the scaffold's potential for targeting multiple disease pathways. Several studies demonstrate that structural modifications on the oxadiazole ring can significantly influence its pharmacokinetic and pharmacodynamic profiles, enabling the design of selective and potent drug candidates. Additionally, it has explored recent advances in synthetic strategies for constructing the 1,2,4-oxadiazole core, such as cyclization reactions involving amidoximes, nitrile oxides, and other precursors. Modern approaches using transition-metal catalysis, microwave-assisted synthesis, and green chemistry techniques are also discussed, emphasizing their importance in improving efficiency and scalability for pharmaceutical applications. Furthermore, the role of 1,2,4-oxadiazole as bioisostere replacement for esters and amides is highlighted, particularly in enhancing metabolic stability and modulating target selectivity. Application of computational methods, including molecular docking and QSAR modeling, have been also covered in understanding ligand-receptor interactions and guiding lead optimization. This review underscores the growing prominence of 1,2,4-oxadiazoles in modern drug design and their potential to address unmet medical needs. With continued research and innovation, these scaffolds are poised to play a pivotal role in the next generation of therapeutic agents across multiple disease areas.

The antioxidant activity of essential oils (EOs) is an important and frequently studied property, yet it is not sufficiently understood in terms of the contribution of EOs mixtures’ constituents and biological properties. In this study, a series of 61 commercial EOs were first evaluated as antioxidants in vitro, following as closely as possible the cellular pathways of reactive oxygen species (ROS) generation. Hence, EOs were assessed for the ability either to chelate metal ions, thus interfering with ROS generation within the respiratory chain, or to neutralize 2,2-diphenyl-1-picrylhydrazyl (DPPH^•) and lipid peroxide radicals (LOO^•), thereby halting lipid peroxidation, as well as to neutralize 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid cation radicals (ABTS^•+) and hydroxyl radicals (OH^•), thereby preventing the ROS species from damaging DNA nucleotides. Showing noteworthy potencies to neutralize all of the radicals at the ng/mL level, the active EOs were also characterized as protectors of DNA double strands from damage induced by peroxyl radicals (ROO^•), emerging from 2,2′-azobis-2-methyl-propanimidamide (AAPH) as a source, and OH^•, indicating some genome protectivity and antigenotoxicity effectiveness in vitro. The chemical compositions of the EOs associated with the obtained activities were then analyzed by means of machine learning (ML) classification algorithms to generate quantitative composition–activity relationships (QCARs) models (models published in the AI4EssOil database available online). The QCARs models enabled us to highlight the key features (EOSs’ chemical compounds) for exerting the redox potencies and to define the partial dependencies of the features, viz. percentages in the mixture required to exert a given potency. The ML-based models explained either the positive or negative contribution of the most important chemical components: limonene, linalool, carvacrol, eucalyptol, α-pinene, thymol, caryophyllene, p-cymene, eugenol, and chrysanthone. Finally, the most potent EOs in vitro, Ylang-ylang (Cananga odorata (Lam.)) and Ceylon cinnamon peel (Cinnamomum verum J. Presl), were promptly administered in vivo to evaluate the rescue ability against redox damage caused by CCl₄, thereby verifying their antioxidant and antigenotoxic properties either in the liver or in the kidney.

In recent years, natural compounds have gained attention in many fields due to their wide-range biological activity. In particular, essential oils and their associated hydrosols are being screened to control plant pests, exerting antiviral, antimycotic and antiparasitic actions. They are more quickly and cheaply produced and are generally considered safer for the environment and non-target organisms than conventional pesticides. In this study, we report the evaluation of the biological activity of two essential oils and their corresponding hydrosols obtained from Mentha suaveolens and Foeniculum vulgare in the control of zucchini yellow mosaic virus and its vector, Aphis gossypii, in Cucurbita pepo plants. The control of the virus was ascertained with treatments applied either concurrently with or after virus infection; choice tests were performed to verify repellency activity against the aphid vector. The results indicated that treatments could decrease virus titer as measured using real-time RT-PCR, while the experiments on the vector showed that the compounds effectively repelled aphids. The extracts were also chemically characterized using gas chromatography–mass spectrometry. Mentha suaveolens and Foeniculum vulgare hydrosol extracts mainly comprised fenchone and decanenitrile, respectively, while essential oils analysis returned a more complex composition, as expected.

A comparative study on essential oils extracted from Mentha suaveolens Ehrh. from Italy is reported. Two extraction procedures were investigated: hydrodistillation and steam distillation, carried out as a continuous and fractionated procedure. Fresh and dried plant material from two harvests was used. The hydrodistillation method yielded a higher amount of essential oil. The dried plant was significantly richer in essential oil per kg of starting plant material. Gas chromatography-mass spectrometry analysis of 112 samples showed that the essential oils belong to the piperitenone oxide-rich chemotype. In addition, piperitenone, p-cymen-8-ol, and limonene were among the most abundant compounds in the different samples. A higher amount of piperitenone oxide was obtained by hydrodistillation, while steam distillation gave a higher percentage of piperitenone and limonene. The essential oils were characterized for their anti-Candida albicans activity; higher potency was observed for the samples rich in piperitenone oxide, with MIC values ranging from 0.39 to 0.78 mg·mL⁻¹ (0.039% and 0.078% p/v). The results of this work provide a deep insight into the methodology of essential oil extraction and the associated chemical variability of M. suaveolens Ehrh. Some of the essential oils are potent against C. albicans and could be considered for potential use in therapy.

Spermidine (SPD) and related polyamines are small polycationic molecules typically elevated in cancer cells, where their depletion suppresses tumor growth both in vitro and in vivo. Paradoxically, SPD has also been proposed as a dietary supplement for its potential health benefits, including cancer prevention, prompting considerable interest in elucidating its mechanisms of action. In vitro studies using cultured cancer cell lines treated with exogenous SPD have yielded conflicting results, with reports of enhanced proliferation, cytotoxicity, or modulation of autophagy. To address these discrepancies, we used polyamine-depleted colorectal cancer (CRC) cells to systematically evaluate SPD's effects across a range of concentrations. Following depletion with difluoromethylornithine, SPD exhibited a biphasic response: at low concentrations (100 µM) induced DHPS-independent cytotoxicity mediated by bovine serum amine oxidase (BSAO) activity in fetal bovine serum. High SPD doses transiently inhibited the autophagic flux, while low doses did not display any effect at all time points tested. The DHPS inhibitor GC7 (N1-guanyl-1,7-diaminoheptane) suppressed SPD-induced proliferation at low concentrations and unexpectedly prevented cytotoxicity at high concentrations. Kinetic assays revealed that GC7 also inhibits BSAO in a non-competitive manner (Ki ≈ 300 nM), independent of DHPS. In silico docking analysis indicated that GC7 binds BSAO via non-covalent interactions, outside the topaquinone organic cofactor site. These findings clarify the concentration-dependent effects of SPD in CRC cells, reconcile conflicting in vitro data, and identify BSAO as a previously unrecognized target of GC7, providing new mechanistic insights into polyamine-driven cancer biology.