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Acetylcholinesterase has been a promising target for the development of putative therapeutics against cognitive decline. The deleterious effect of oxidative stress on the learning and memory paradigms of an individual has also been well documented. In view of this, the present study demonstrates the design, synthesis and pharmacological evaluation of triazole-oxadiazole conjugates. Eighteen novel hybrids (6-23) have been synthesised by employing suitable synthetic procedures and characterized by various spectral and elemental techniques. Further these synthesised compounds were evaluated against behavioural alterations using step down passive avoidance and escape learning protocol at a dose of 0.5 mg/kg with reference to the standard, donepezil. All the synthesised compounds were evaluated for their in vitro acetylcholinesterase (AChE) inhibition at five different concentrations using mice brain homogenate as the source of the enzyme. Biochemical estimation of markers of oxidative stress (lipid peroxidation, superoxide dismutase, glutathione and catalase) has also been carried out to assess the role of synthesised molecules on the oxidative damage induced by scopolamine. The compounds 13, 17 and 23 displayed appreciable activity towards acetylcholinesterase inhibition. These compounds also decreased scopolamine induced oxidative stress, thus serving as promising leads for the amelioration of oxidative stress induced cognitive decline. The molecular docking study performed to predict the binding mode of the compounds also suggested that these compounds bind appreciably to the amino acids present in the active site of the recombinant human acetylcholinesterase (rhAChE). The results indicated that these compounds could be further traversed as inhibitors of AChE and oxidative stress for the treatment of cognitive dysfunction.PROteolysis TArgeting Chimeras (PROTACs) are heterobifunctional molecules that trigger the poly-ubiquitination of the protein of interest (POI) inducing its degradation via the recruitment of the ubiquitin-proteasome system, thus suppressing the POI’s intracellular levels and indirectly all its functions. Recently, one of the fields where the protein knockdown induced by PROTACs has demonstrated to serve as a promising biochemical tool and to provide new opportunities for drug discovery is the epigenetics (epi-PROTACs). A full inhibition of the functions of all domains of a specific epigenetic POI (e-POI), rather than just the block of its catalytic/single domain activity, is in fact a new more effective modality to hit an e-POI and, in principle, the complex it belongs to, and potentially to treat the related diseases, first cancer. In this review, we will present the most relevant progresses made, especially in the last two years, in the application of PROTACs technology to the three main classes of e-POIs “writers”, “erasers” and “readers”. Emphasis will be devoted to the medicinal chemistry aspects of the epi-PROTACs design, preparation, and optimization and to the comparison with small molecule epi-drugs for both epi-targets functional annotation and potential anticancer therapy purposes.Diabetes mellitus is a metabolic disease characterized by high blood glucose levels and usually associated with several chronic pathologies. Aldose reductase and protein tyrosine phosphatase 1B enzymes have identified as two novel molecular targets associated with the onset and progression of type II diabetes and related comorbidities. Although many inhibitors against these enzymes have already found in the field of diabetic mellitus, the research for discovering more effective and selective agents with optimal pharmacokinetic properties continues. In addition, dual inhibition of these target proteins has proved as a promising therapeutic approach. A variety of diverse scaffolds are presented in this review for the future design of potent and selective inhibitors of aldose reductase and protein tyrosine phosphatase 1B based on the most important structural features of both enzymes. The discovery of novel dual aldose reductase and protein tyrosine phosphatase 1B inhibitors could be effective therapeutic molecules for the treatment of insulin-resistant type II diabetes mellitus. The methods used comprise a literature survey and X-ray crystal structures derived from Protein Databank (PDB). Despite the available therapeutic options for type II diabetes mellitus, the inhibitors of aldose reductase and protein tyrosine phosphatase 1B could be two promising approaches for the effective treatment of hyperglycemia and diabetes-associated pathologies. Due to the poor pharmacokinetic profile and low in vivo efficacy of existing inhibitors of both targets, the research turned to more selective and cell-permeable agents as well as multi-target molecules.Vibrio harveyi is a marine bacterial pathogen which infects a wide range of marine organisms and results in severe loss. Antibiotics have been used for prophylaxis and treatment of V. selleck compound harveyi infection. However, antibiotic resistance is a major public health threat to both human and animals. Therefore, there is an urgent need for novel antimicrobial agents with new modes of action. In V. harveyi, many virulence factors production and bioluminescence formation depend on its quorum sensing (QS) network. Therefore, the QS system has been widely investigated as an effective potential target for the treatment of V. harveyi infection. This perspective focuses on the quorum sensing inhibitors (QSIs) of V. harveyi QS systems (LuxM/N, LuxS/PQ, and CqsA/S) and evaluates medicinal chemistry strategies.The Strategic Plan for Biodefense Research by the U.S. Department of Health and Human Services demarcates the need for drugs which target multiple types of pathogens to prepare for infectious threats. Azithromycin is one such broad-spectrum therapeutic that is both included in the University of Oxford’s RECOVERY and excluded from the World Health Organization’s SOLIDARITY trials. Here we review azithromycin’s broad antibiotic, antimalarial, antiviral pharmacology and contextualise it against a broader history as the most repositioned therapeutic of the macrolide class; we further evaluate azithromycin’s clinical and socio-economic propriety for respiratory pandemics and delineate a model for its combinatorial mechanism of action against COVID-19 pneumonia.