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.

Bacterial cystathionine γ-lyase (bCSE) is the main producer of H₂S in pathogenic bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, etc. The suppression of bCSE activity considerably enhances the sensitivity of bacteria to antibiotics. Convenient methods for the efficient synthesis of gram quantities of two selective indole-based bCSE inhibitors, namely (2-(6-bromo-1H-indol-1-yl)acetyl)glycine (NL1), 5-((6-bromo-1H-indol-1-yl)methyl)- 2-methylfuran-3-carboxylic acid (NL2), as well as a synthetic method for preparation 3-((6-(7-chlorobenzo[b]thiophen-2-yl)-1H-indol-1-yl)methyl)- 1H-pyrazole-5-carboxylic acid (NL3), have been developed. The syntheses are based on the use of 6-bromoindole as the main building block for all three inhibitors (NL1, NL2, and NL3), and the designed residues are assembled at the nitrogen atom of the 6-bromoindole core or by the substitution of the bromine atom in the case of NL3 using Pd-catalyzed cross-coupling. The developed and refined synthetic methods would be significant for the further biological screening of NL-series bCSE inhibitors and their derivatives.

Polymers from norbornenes are of interest for applications in opto- and microelectronic (low dielectric materials, photoresists, OLEDs). Norbornenes with ester motifs are among the most readily available norbornene derivatives. However, little is known about dielectric properties and the gas-transport of polynorbornenes from such monomers. Herein, we synthesized a new metathesis polymer from exo-5-norbornenecarboxylic acid and 1,1′-bi-2-naphthol. The designed monomer was obtained via a two-step procedure in a good yield. This norbornene derivative with a rigid and a bulky binaphthyl group was successfully polymerized over the 1st generation Grubbs catalyst, affording high-molecular-weight products (M_w ≤ 1.5·10⁶) in yields of 94–98%. The polymer is amorphous and glassy (T_g = 161 °C), and it shows good thermal stability. Unlike most, polyNBi is a classic low-permeable glassy polymer. The selectivity of polyNBi was higher than that of polyNB. Being less permeable than polyNB, polyNBi unexpectedly showed a lower value of dielectric permittivity (2.7 for polyNBi vs. 5.0 for polyNB). Therefore, the molecular design of polynorbornenes has great potential to obtain polymers with desired properties in a wide range of required characteristics. Further tuning of the gas separation efficiency can be achieved by attaching an appropriate substituent to the ester and aryl group.

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.

Heptose phosphates—unique linkers between endotoxic lipid A and O-antigen in the bacterial membrane—are pathogen-associated molecular patterns recognized by the receptors of the innate immune system. Understanding the mechanisms of immune system activation is important for the development of therapeutic agents to combat infectious diseases and overcome antibiotic resistance. However, in practice, it is difficult to obtain a substantial amount of heptose phosphates for biological studies due to the narrow scope of the reported synthetic procedures. We have optimized and developed an inexpensive and convenient synthesis for the first performed gram-scale production of 1-O-methyl d-glycero-α-d-gluco-heptoside 7-phosphate from readily available d-glucose. Scaling up to such amounts of the product, we have increased the efficiency of the synthesis and reduced the number of steps of the classical route through the direct phosphorylation of the O⁶,O⁷-unprotected heptose. The refined method could be of practical value for further biological screening of heptose phosphate derivatives.