Current Topics in Medicinal Chemistry - Volume 24, Issue 25, 2024

Acute respiratory distress syndrome in the elderly with COVID-19 complicated by airway obstruction with sputum and mucus, and cases of asphyxia with blood, serous fluid, pus, or meconium in newborns and people of different ages can sometimes cause hypoxemia and death from hypoxic damage to brain cells, because the medical standard does not include intrapulmonary injections of oxygen-producing solutions. The physical-chemical repurposing of hydrogen peroxide from an antiseptic to an oxygen-producing antihypoxant offers hope for the development of new drugs.

This manuscript is a meta-analysis performed according to PRISMA guidelines.

It is shown that replacement of the traditional acidic activity of hydrogen peroxide solutions by alkaline activity with pH 8.4 and heating the solutions to the temperature of +37 - +42 ℃ allows to repurpose hydrogen peroxide from antiseptics into inhalation and intrapulmonary mucolytics, pyolytics and antihypoxants releasing oxygen. The fact is that warm alkaline hydrogen peroxide solution (WAHPS) in local interaction with sputum, mucus, pus, blood and meconium provides optimal conditions for the metabolism of hydrogen peroxide to oxygen gas under the action of the enzyme catalase, always present in these tissues. It was established that WAHPS liquefies these biological masses due to alkaline saponification of lipid and protein-lipid complexes and simultaneously transforms dense masses into soft oxygen foam due to active enzymatic metabolism of hydrogen peroxide to oxygen gas, the rapidly appearing bubbles of which are formed by the type of “cold boiling” and literally explode these masses. The results of the first experiments showed that inhalation and intrapulmonary injections of WAHPS can significantly optimize the treatment of suffocation and hypoxemia.

The results showed that catalase, which is found in sputum, mucus, pus, and blood, may be a target for localized WAHPS because this enzyme provides an intensive metabolism of hydrogen peroxide to oxygen gas up to the formation of the cold boiling process.

These data provide a new perspective way for intrapulmonary drugs and new technologies for the emergency increase of blood oxygenation through the lungs in asphyxia with thick sputum, mucus, pus, meconium and blood.

Oxidative response is a risk factor in the progression of arterial atherosclerosis.

This research study aimed to examine the effects of oxidative response on atherosclerotic susceptibility as well as the development of arteriosclerosis occlusions of the tibial artery through pro-inflammatory mediator genes in elderly patients with occlusion of coronary arteries.

We determined that oxidative stress biomarkers (Malondialdehyde-modified Low-density Lipoprotein (MDA-LDL), Oxidized Low-density Lipoprotein (Ox-LDL) as well as Heme Oxygenase-1 (HO-1)] and the expressions of pro-inflammatory mediator genes [Toll-like Receptor 4 (TLR4), Nuclear Factor kappa-B (NF-κB), Myeloid Differentiating factor 88 (MyD88) and Growth Arrest-specific gene 6 (GAS6)] have an impact on the severity of arteriosclerosis occlusions of tibial artery in elderly patients suffering from occlusion of coronary arteries.

Levels of MDA-LDL, Ox-LDL, HO-1, TLR4, NF-κB, MyD88, and GAS6 were increased in the occlusion of tibial arteries + two-vessel coronary occlusion group compared to the CON group and occlusion of tibial arteries + one-vessel coronary occlusion group, respectively (p < 0.001); they were also elevated in occlusion of tibial arteries + multiple-vessel coronary occlusion group compared to occlusion of tibial arteries + one-vessel coronary occlusion group and occlusion of tibial arteries + two-vessel coronary occlusion group, respectively (P < 0.001). This has indicated the key roles of oxidative stress and pro-inflammatory mediator genes in arteriosclerosis occlusions of tibial artery in elderly patients with occlusion of coronary arteries.

Oxidative response may promote the expressions of inflammatory genes and enhance susceptibility to arteriosclerosis occlusions of the tibial artery in elderly patients with chronic total coronary occlusions.

In this study, we have synthesized 19 Thiazolidine (TZD) derivatives to investigate their potential anti-ZIKV effects.

Nineteen thiazolidine derivatives were synthesized and evaluated for their cytotoxicity and antiviral activity against the ZIKA virus.

Among them, six demonstrated remarkable selectivity against the ZIKV virus, exhibiting IC50 values of <5µM, and the other compounds did not demonstrate selectivity for the virus. Interestingly, several derivatives effectively suppressed the replication of ZIKV RNA copies, with derivatives significantly reducing ZIKV mRNA levels at 24 hours post-infection (hpi). Notably, two derivatives (ZKC-4 and -9) stood out by demonstrating a protective effect against ZIKV cell entry. Informed by computational analysis of binding affinity and intermolecular interactions within the NS5 domain's N-7 and O'2 positions, ZKC-4 and FT-39 displayed the highest predicted affinities. Intriguingly, ZKC-4 and ZKC-9 derivatives exhibited the most favorable predicted binding affinities for the ZIKV-E binding site.

The significance of TZDs as potent antiviral agents is underscored by these findings, suggesting that exploring TZD derivatives holds promise for advancing antiviral therapeutic strategies.

The available literature indicates that Hyssopus officinalis and Grindelia robusta are raw materials with great potential for use in prevention and therapy. Therefore, the aims of this study were to assess the phytochemical profile and antioxidant and cytoprotective properties of extracts prepared using various solvents, additionally taking into account different methods of drying the plant material.

Hydrodistilled oil was analysed by GC-MS. The chemical composition of the extracts was estimated by spectrophotometry and the HPLC-DAD method. Antioxidant activity was evaluated using DPPH and FRAP and measuring the intracellular level of ROS. Alamar Blue and Neutral Red tests were used to assess the cytotoxicity of the extracts on skin cells - keratinocytes and fibroblasts.

The major components of hyssop essential oil were cis- (44.9%) and trans- (18.2%) pinocamphone, while borneol (16.1%), and α-pinene (12.0%) were predominant in grindelia essential oil. Flavonoids were dominant in the extracts (water: ethanol, water: methanol, and water: glycerol) from hot-air dried hyssop herb, while phenolic acids were the predominant compounds in the grindelia herb extracts. The water: ethanol hyssop extract had the highest total content of flavonoids (42.26 mg CE/mL), among which isoquercitrin and rutin were present in the highest quantities (32.61 mg/mL and 21.47 mg/mL, respectively). In the case of grindelia, the highest total phenolic acid content (26.24 mg CAE/mL) was recorded in the water: ethanol extract, and the dominant compounds among them were 1,5-dicaffeoylquinic and chlorogenic acid (10.85 and 6.39 mg/mL, respectively). The water: ethanol extract from both plants also exhibited the highest antioxidant activity in the DPPH and FRAP tests (79.19% and 1.39 mmol/L, respectively, for grindelia and 67.61% and 1.04 mmol/L for hyssop) and was most effective at reducing the level of ROS in cells. In addition, water: ethanol extracts may have a positive impact on the viability of skin cells in vitro.

Water:ethanol extracts from H. officinalis and G. robusta herb are promising sources of active compounds and may find application as natural materials with valuable biological properties, which require further in vitro and in vivo testing.