Reactions of quinones with compounds containing an amino group can produce a wide variety of addition or substitution products that depend on reactivity of both quinone and amino derivative. 6,7-Dichloropyrido[1,2-a]benzimidazole-8,9-diones undergo selective nucleophilic substitution reaction with different benzohydrazides and α-hydroxy-p-quinone imine derivatives stabilized by strong intramolecular hydrogen bond were isolated. Synthesized compounds represent a combination of several structural motifs: benzimidazole core fused with α-hydroxy-p-quinone imine which contains a benzamido fragment. The protonation/deprotonation processes were investigated in a solution using UV-Vis spectroscopy and 1H NMR titration experiment. X-ray crystallography analysis revealed a set of weak non-covalent interactions such as intra- and intermolecular hydrogen bonds and π-π stacking. Additionally, the redox behavior of 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione and its p-imino derivative was investigated in acidic and neutral environment using cyclic voltammetry measurements. Cathode material based on 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione could act as potential effective active electrode in aqueous electrolyte batteries, however further optimization is required.

Plant flavonoids have increasingly paid a close attention to for new antimicrobial agents or adjuvants. In our previous work, it was confirmed that the cell membrane is the major site of plant flavonoids acting on the gram-positive bacteria, and which likely involves the inhibition of the respiratory chain. Inspired by the similar structural and antioxidant characters of plant flavonoids to MKH₂, we deduced that the quinone pool is probably a key target of plant flavonoids inhibiting gram-positive bacteria. To verify this, twelve plant flavonoids with six structural subtypes were preliminary selected, and their MICs against gram-positive bacteria were predicted from the antimicrobial quantitative relationship of plant flavonoids to gram-positive bacteria. The results showed they have different antimicrobial activities. After their MICs against S. aureus were determined using broth microdilution method, nine compounds with the MICs ranged from 2 to 4,096 μg/mL or more than 1,024 μg/mL were eventually selected, and then their MICs against S. aureus were determined interfered with different concentrations of MK-4 and the MKs extracted from S. aureus. The results showed that the greater the antibacterial activities of plant flavonoids were, the more greatly their antibacterial activities decreased along with the increase of the interfering concentrations of MK-4 (from 2 to 256 μg/mL) and MK extract (from 4 to 512 μg/mL), and while those, with the MICs equal to or more than 512 μg/mL, decreased a little or remained unchanged. Especially, under the interference of MK-4 (256 μg/mL) and MK extract (512 μg/mL), the MICs of α-mangostin, a compound with greatest inhibitory activity to S. aureus in these twelve plant flavonoids, increased by 16 times and 8 to16 times, respectively. Based on these above, it was proposed that the quinone pool is a key target of plant flavonoids inhibiting gram-positive bacteria, and which likely involves multiple mechanisms including some enzyme and non-enzyme inhibitions.

Short chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which is largely dependent on their reversible redox characteristics of the active quinone core. We recently synthesized a SCQ library of > 148 naphthoquinone derivatives and identified 16 compounds with enhanced cytoprotection compared to the clinically used benzoquinone idebenone. One of the major drawbacks of idebenone is its high metabolic conversion in the liver, which significantly restricts is therapeutic activity. Therefore, this study assessed the metabolic stability of the 16 identified naphthoquinone derivatives 1-16 using hepatocarcinoma cells in combination with an optimized reverse-phase liquid chromatography (RP-LC) method. Most of the derivatives showed significantly better stability than idebenone over 6 hours (p < 0.001). By extending the side-chain of SCQs, increased stability for some compounds was observed. Metabolic conversion from the derivative 3 to 5 and reduced idebenone metabolism in the presence of 5 were also observed. These results highlight the therapeutic potential of naphthoquinone-based SCQs and provide essential insights for future drug design, prodrug therapy and polytherapy, respectively.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results &amp; conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.