NADPH oxidase enzymes (NOXs) are a family of enzymes generating superoxide, which form reactive oxygen species. NOX2 activity is a causative agent for the progression of many diseases: neurodegenerative, cardiovascular, immune dysregulations, and even hereditary diseases and cancer. Administering antioxidants helps in inhibiting NOX2 activity; however, the development of selective inhibitors may provide greater improvement in the therapy of diseases. Here, an optimized synthesis of two most promising NOX2 inhibitors based on the 3-(indolin-6-yl)-4-(N-pyrazole-sulfonamide)-1H-pyrrolo [2,3-b]pyridine structure, namely, GSK2795039 and NCATS-SM7270, and an isomeric derivative of the same class, IMBIOC-1, is reported. The new modified procedures simplify the isolation, reduce byproduct formation, and improve the yields in 0.1–1 g scale preparations. Molecular modeling of the structures of NOX2 complexes with inhibitors validated their binding at the same site as NADPH, with IMBIOC-1 forming the largest number of intermolecular interactions with the NOX2 active site. Testing the effects of the compounds on amyloid beta-induced oxidative stress and toxicity in HMC3 microglial cells showed that all three inhibitors completely prevented the pathological amyloid-beta effect. At the same time, NCATS-SM7270 and IMBIOC-1 provided a stronger protective effect on microglial cell survival than GSK2795039, which allowed us to assert the potential of those compounds as neuroprotective agents.

In recent years, a number of synthetic potentiators of antibiotics have been discovered. Their action can significantly enhance the antibacterial effect and limit the spread of antibiotic resistance through inhibition of bacterial cystathionine-γ-lyase. To expand the known set of potentiators, we developed methods for the synthesis of five new representatives of 6-bromoindole derivatives—potential inhibitors of bacterial cystathionine-γ-lyase—namely potassium 3-amino-5-((6-bromoindolyl)methyl)thiophene-2-carboxylate (MNS2) and its 6-bromoindazole analogs (MNS3 and MNS4), along with two 6-broindazole analogs of the parent compound NL2. Their syntheses are based on 6-bromoindole, 6-bromoindazole and methyl 5-(bromomethyl)-3-((ethoxycarbonyl)amino)thiophene-2-carboxylate as the main building blocks, assembling the rest of the heterocyclic system on their basis at the nitrogen atom. We assessed the ability of the new inhibitors to potentiate the antimicrobial activity of gentamicin.

A reactivity umpolung approach for the derivatization of cycloheptatrienes was extended to hexa(methoxycarbonyl)cycloheptatriene, which forms the corresponding anion reactive towards electrophiles. Despite the presence of four potential reactive sites, the reactions mainly involve the initial electrophilic attack onto the α-position relative to the hydrogen atom. The selectivity is either due to the high stability of the α-nucleophilic conformer or due to the promotion by the adjacent ester group. Cascade reactions upon the target connection, if installed, include the formation of norcaradienes, dihydroindazoles, a tetracyclodecene and a hydrazonocycloheptatriene derivative.