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Introduction: Aldose reductase (AKR1B1, EC: 1.1.1.21) is a recognized target for the treatment of long-term diabetic complications since its activation in hyperglycemia and role in the polyol pathway. In particular, the tissue-specificity of AKR1B1 expression makes the design of the traditional Aldose Reductase Inhibitors (ARIs) and the more recent Aldose Reductase Differential Inhibitors (ARDIs) exploitable strategies to treat pathologies resulting from diabetic conditions., Areas Covered: A brief overview of the roles and functions of AKR1B1 along with known ARIs and ARDIs was provided. Then, the design of the latest inhibitors in the scientific scenario was discussed, aiming at introducing the research achievement in the field of intellectual properties. Patents dealing with AKR1B1 and diabetes filed in the 2019-2023 period were collected and analyzed. Reaxys, Espacenet, SciFinder n , and Google Patents were surveyed, using 'aldose reductase' and 'inhibitor' as the reference keywords. The search results were then filtered by PRISMA protocol, thus obtaining 16 records to review., Expert Opinion: Although fewer in number than in the early 2000s, patent applications are still being filed in the field of ARIs, with a large number of Chinese inventors reporting new synthetic ARIs in favor of the repositioning approach.

Aldehyde dehydrogenases of the subfamily 1A (ALDH1A) are enzymes necessary for the oxidation of all- trans or 9- cis retinal to retinoic acid (RA). Retinoic acid and its derivatives are important for normal development and maintenance of epithelia, reproduction, memory, and immune function in adults. Moreover, in recent years, it has been demonstrated that ALDH1A members are also expressed and functional in several human cancers where their role is not limited to the synthesis of RA. Here, we review the current knowledge about ALDH1A3, one of the 1A isoforms, in cancers with an emphasis on two of the deadliest tumors that affect humans: glioblastoma multiforme and mesothelioma. In both tumors, ALDH1A3 is considered a negative prognostic factor, and its level correlates with excessive proliferation, chemoresistance, and invasiveness. We also review the recent attempts to develop both ALDH1A3-selective inhibitors for cancer therapy and ALDH1A3-specific fluorescent substrates for fluorescence-guided tumor resection., Competing Interests: S.G. and L.M. are among the holders of the patent “PROBE DIRECTED TO ENZYME ALDH1A3 AND USE THERE OF IN THE DIAGNOSIS OF GLIOBLASTOMA” PCT/IB2022/053216 (6 April 2022); International Application. All the other authors have no conflicts of interest to declare. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

The proteolytic activity of the enzyme ADAMTS7 was recently shown to enhance the progression of atherosclerosis, in line with human genetic findings suggesting that ADAMTS7 has a role in the pathophysiology of coronary heart disease. Targeting the active site of ADAMTS7 with a small molecule inhibitor, therefore, has therapeutic potential. Here, we report the design and synthesis of a novel hydroxamate-based arylsulfonamide that is a potent and selective ADAMTS7 inhibitor. In silico studies guided the hit optimization process aiming to improve selectivity of the previously reported (non-selective) inhibitor EDV33. Our lead compound is a p -trifluoromethyl biphenyl sulfonamide, which displayed a 12-fold selectivity for ADAMTS7 ( K i = 9 nM) over ADAMTS5 ( K i = 110 nM) and an 8-fold increase in inhibition of ADAMTS7 compared to EDV33 ( K i = 70 nM). The substitutions switched selectivity and produced a new potent ADAMTS7 inhibitor that can be taken forward for further characterisation., Competing Interests: No potential conflict of interest was reported by the authors., (This journal is © The Royal Society of Chemistry.)

Introduction: The oral cavity harbors an extensive array of over 700 microorganisms, forming the most complex biome of the entire human body, with bacterial species being the most abundant. Oral diseases, e.g. periodontitis and caries, are strictly associated with bacterial dysbiosis. Porphyromonas gingivalis and Streptococcus mutans stand out among bacteria colonizing the oral cavity., Areas Covered: After a brief overview of the bacterial populations in the oral cavity and their roles in regulating (flora) oral cavity or causing diseases like periodontal and cariogenic pathogens, we focused our attention on P. gingivalis and S. mutans , searching for the last-5-year patents dealing with the proposal of new strategies to fight their infections. Following the PRISMA protocol, we filtered the results and analyzed over 100 applied/granted patents, to provide an in-depth insight into this R&D scenario., Expert Opinion: Several antibacterial proposals have been patented in this period, from both chemical - peptides and small molecules - and biological - probiotics and antibodies - sources, along with natural extracts, polymers, and drug delivery systems. Most of the inventors are from China and Korea and their studies also investigated anti-inflammatory and antioxidant effects, being beneficial to oral health through a prophylactic, protective, or curative effect.

Infections from Helicobacter pylori (Hp) are endangering Public Health safety worldwide, due to the associated high risk of developing severe diseases, such as peptic ulcer, gastric cancer, diabetes, and cardiovascular diseases. Current therapies are becoming less effective due to the rise of (multi)drug-resistant phenotypes and an urgent need for new antibacterial agents with innovative mechanisms of action is pressing. Among the most promising pharmacological targets, Carbonic Anhydrases (EC: 4.2.1.1) from Hp, namely HpαCA and HpβCA, emerged for their high druggability and crucial role in the survival of the pathogen in the host. Thereby, in the last decades, the two isoenzymes were isolated and characterized offering the opportunity to profile their kinetics and test different series of inhibitors., (Copyright © 2024. Published by Elsevier Inc.)

Matrix metalloproteinase 13 plays a central role in osteoarthritis (OA), as its overexpression induces an excessive breakdown of collagen that results in an imbalance between collagen synthesis and degradation in the joint, leading to progressive articular cartilage degradation. Therefore, MMP-13 has been proposed as a key therapeutic target for OA. Here we have developed a virtual screening workflow aimed at identifying selective non-zinc-binding MMP-13 inhibitors by targeting the deep S1' pocket of MMP-13. Three ligands were found to inhibit MMP-13 in the µM range, and one of these showed selectivity over other MMPs. A structure-based analysis guided the chemical optimization of the hit compound, leading to the obtaining of a new N -acyl hydrazone-based derivative with improved inhibitory activity and selectivity for the target enzyme.