Oxadiazole is a five-membered heterocyclic compound containing two nitrogen atoms and one oxygen atom. The 1,3,4-oxadiazole and 1,2,4-oxadiazole have favourable physical, chemical, and pharmacokinetic properties, which significantly increase their pharmacological activity via hydrogen bond interactions with biomacromolecules. In recent years, oxadiazole has been demonstrated to be the biologically active unit in a number of compounds. Oxadiazole derivatives exhibit antibacterial, anti-inflammatory, anti-tuberculous, anti-fungal, anti-diabetic and anticancer activities. In this paper, we report a series of compounds containing oxadiazole rings that have been published in the last three years only (2020–2022) as there was no report or their activities described in any article in 2019, which will be useful to scientists in research fields of organic synthesis, medicinal chemistry, and pharmacology.

Advanced glycation end products (AGEs) are stable products produced by the reaction of macromolecules such as proteins, lipids or nucleic acids with glucose or other reducing monosaccharides, which can be identified by immunohistochemistry in the senile plaques and neurofibrillary tangles of Alzheimer’s disease (AD) patients. Growing evidence suggests that AGEs are important risk factors for the development and progression of AD. 1,8-cineole (CIN) is a monoterpenoid compound which exists in many plant essential oils and has been proven to have neuroprotective activity, but its specific effect and molecular mechanisms are not clear. In this study, AGEs-induced neuronal injury and intracerebroventricular-AGE animals as the possible models for AD were employed to investigate the effects of CIN on AD pathology as well as the molecular mechanisms involved both in vivo and in vitro. Our study demonstrated that CIN could ameliorate tau phosphorylation by down-regulating the activity of GSK-3β and reducing Aβ production by inhibiting the activity of BACE-1 both in vivo and in vitro. It is suggested that CIN has certain therapeutic value in the treatment of AD.

A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a–5v) exerted neuroprotective effects on β-amyloid (Aβ)-induced PC12 cells as a potential approach for the treatment of Alzheimer’s disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aβ_25-35-induced PC12 cells at 5 μg/mL. We found that compound 5c was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ_25-35-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ_25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aβ_25-35-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3β/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.

In this study, a new series of quinoxalinone derivatives (5a–5p, 6a–6n) was designed and its hypoglycemic activity was evaluated. The results showed that compounds 5i and 6b exhibited stronger hypoglycemic effects than the lead compounds and were comparable to the positive control Pioglitazone. 5i and 6b may exert hypoglycemic effects by alleviating cellular OS and modulating the interactions among GLUT4, SGLT2, and GLUT1 proteins. The alleviating cellular OS of compound 6b was better than that of 5i, and 6b was found to bind better than 5i for most of the screening targets. In summary, compound 6b is a potential lead compound with hypoglycaemic activity.3

Alzheimer’s disease (AD) is a major neurodegenerative disease, but so far, it can only be treated symptomatically rather than changing the process of the disease. Recently, triazoles and their derivatives have been shown to have potential for the treatment of AD. In this study, the neuroprotective effects of 4-(4-(heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (W112) against β-amyloid (Aβ)-induced AD pathology and its possible mechanism were explored both in vitro and in vivo. The results showed that W112 exhibits a neuroprotective role against Aβ-induced cytotoxicity in PC12 cells and improves the learning and memory abilities of Aβ-induced AD-like rats. In addition, the assays of the protein expression revealed that W112 reversed tau hyperphosphorylation and reduced the production of proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, both in vitro and in vivo studies. Further study indicated that the regulation of mitogen-activated protein kinase/nuclear factor-κB pathways played a key role in mediating the neuroprotective effects of W112 against AD-like pathology. W112 may become a potential drug for AD intervention.

While a range of pharmacological agents are currently used to alleviate inflammation, the clinical administration of many of these anti-inflammatory drugs is associated with high rates of adverse side effects that make them poorly suited to long-term use. Therefore, there is a critical need for the development of novel anti-inflammatory agents. Natural compounds and derivatives like ethyl ferulate have risen to prominence as a foundation for many drug discovery efforts owing to their structural diversity and wide-ranging biological activities. In the present study, 24 ethyl ferulate derivatives were synthesized. Their anti-inflammatory activity was evaluated in vitro using RAW264.7 cells and CCK-8, ELISA, and Western blotting assays. These analyses revealed that most of the synthesized compounds exhibited moderate to high anti-inflammatory activities. In particular, c10 and c23 exerted more pronounced activity than ethyl ferulate or dexamethasone with respect to the suppression of tumour necrosis factor-α production by RAW264.7 cells through the targeting of the NF-κB and MAPK signalling pathways, suggesting that these compounds warrant further investigation. Graphical Abstract