Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with motor symptoms (tremor, rigidity, etc.) as well as cognitive and behavioral problems. Nowadays, Levodopa, the main drug for Parkinson’s disease treatment, has serious side effects, including forgetfulness, headache, etc. For that reason, development of new drug for effective treatment of PD is extremely important. Recently, it was found in Novosibirsk Institute of Organic Chemistry that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (1) demonstrated high anti-Parkinsonian activity in vivo on animal models in mice and rats.

Subsequently, several modifications of 1 at different sites were carried out. Although most modifications led to decrease in activity, a few new compounds demonstrated promising anti-Parkinsonian activity. Here, we present stereoselective synthesis of (1R,2R,6S)-2-(1H-1,2,4-triazol-3-ylthio)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-enol (2) with the same stereochemistry of all asymmetric centers as in parent compound 1. It was shown that derivative 2 demonstrates high anti-PD in mice MPTP and haloperidol models of Parkinson’s disease as well as restoration of dopamine concentration in midbrain.

Prenatal hypoxia (PH) causes pathological changes in the brain and can lead to irreversible long-term disorders of its development and the emergence of neuropsychiatric pathologies in children. Pharmacological correction of posthypoxic CNS disorders is a priority problem in modern medicine. The aim of this research was to study the neuroprotective action of drugs with an evidence-based effect on the expression – angiolin, thiotriazoline, tamoxifen, glutoredoxin, cerebrocurin, mexidol and L-arginine in comparison with the reference drug piracetam in terms of their effect on the expression of endogenous neuroprotection factors to further substantiate their use in the treatment of prenatal CNS damage in a model of chronic hemic PH. Expression levels of mRNA HSP₇₀, HIF-1, c-fos and the content of HSP₇₀ in the cytoplasmic and mitochondrial fractions of the brain of rat on the 60th day of life after PH were determined by real-time PCR and enzyme immunoassay. It has been established that chronic PH production inhibits transcriptional processes in neurons and suppresses the synthesis of HIF1a, HSP₇₀ and c-fos. The studied drugs are able to modulate HSP₇₀-mediated mechanisms of endogenous neuroprotection. The most active among HSP₇₀ modulators in conditions of chronic PH are cerebrocurin (150 µl/kg) and angiolin (50 mg/kg), which outperform other studied drugs in terms of increased expression of HSP₇₀, mRNA, HIF-1α mRNA, and HSP₇₀, protein concentration in the brain of experimental animals and can be considered as promising neuroprotective agents in complex therapy after PH.

There is tremendous expansion in use of traditional medicines worldwide. About three quarters of the world population relies on plants and plant extracts for health care. The major challenges in acceptance of herbal medicines are quality, safety and scientific evidence in relation to their health claims. The topical gel formulations are more preferred due to various advantages such as easy to administer, rapid in action, less greasy and cost effective. Thus the present work focus on preparation of polyherbal gels using varied proportions of traditionally reported plants such as essential oil of Murraya koenigii, gel of Aloe vera, hydroalcoholic extract of leaves of Tridax Procumbens. The prepared polyhebal gels evaluated for their antibacterial activity using agar cup method. The more effective antibacterial polyherbal gel evaluated for physical parameters such as pH, homogeneity, viscosity, extrudability, spreadability, stability. Polyherbal gel formulation F1, F2 and F3 showed antibacterial activity against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. Polyherbal gel formulation F3 showed significant antibacterial activity compare to standard marketed formulations (betadine ointment). The prepared polyherbal gel formulation F3 has good homogeneity, spreadability, extrudability, stability without any irritation effect on skin.

At the end of the last century, it was revealed that quinones with one, two, and three aromatic rings could inhibit HIV-1 protease, an enzyme crucial for HIV (Human Immunodeficiency Virus) replication. Since HIV-1 protease acts as key target for AIDS medications (Acquired immunodeficiency syndrome), the development of efficient inhibitor of this protein would lead to the increasing of the medical treatment, and decreasing of the drug resistance. Later research revealed that simply hydroxyquinones can block HIV-1 protease at the micromolar level, which enabled a direction for the creation of HIV medications. Anthrarufin (1,5-dihydroxy-9,10-anthraquinone) is an anthraquinone that posses a moderate antioxidative capacity and antimalaric activity. In this study, molecular docking simulations were used to examine the molecular interactions between anthrarufin, its monoanion and dianion as ligands, and the HIV-1 reverse transcriptase (HIV-1 RT) as target protein. Using AGFR software, the binding site of the HIV-1 RT is identified. The three-dimensional crystal structure of HIV-1 RT is downloaded from the Protein Data Bank (PDB ID: 2ZD1). Dolutegravir, nevirapine, anthrarufin, anthrarufin-anion and anthrarufin-dianion are used as ligands in the molecular docking simulations together with rilpivirine (TMC278), a non-nucleoside inhibitor of estimated protein. The AutoDock 4.0 program is used for molecular docking simulations. Anthrarufin, its monoanion and dianion can be considered as a potential HIV-1 RT inhibitors because they have similar inhibitory potency to other ligands under consideration, according to the results of the free energy of binding (∆G_bind) and inhibition constant (K_i) values.

Nutraceutical is a field of treatment which is gained more attention from people in recent times. Dietary polyphenols, as a part of nutraceutical products, constitute two groups. Hydroxycinnamic acid is one of those two groups. These acids are found naturally in various products we consume on a day-to-day basis. Coffee is one of the most common sources of hydroxycinnamic acids. Cinnamon is a spice that is consumed in different forms in various food products. The study presented investigates their capacity as anti-oxidant agents and anti-microbial agents through in-vitro and in-silico approaches. For this, commonly found infectious organisms namely, E. coli, S. aureus, K. pneumoniae, and S. pyogenes were cultured. The minimum inhibitory concentration for methanolic coffee extract as well as methanolic cinnamon extract was estimated to be ~0.4 ug/ml and ~5 ug/ml. The cytotoxicity effect of these extracts was studied on cell line ie. MCF-7 (human breast cancer cell line). IC50 values for MCF-7 were calculated at 64.04 μg/ml for coffee extract, 81.12 μg/ml for cinnamon extract, and 51.14 μg/ml for standard caffeic acid. Molecular docking analysis revealed the efficiency of different hydroxycinnamic acids on protein receptors namely, PPAR, IL-6, TNF- alpha, and VEGF. These results were supported by the tests performed on blood cultures and human tissue samples obtained from the clinical partner. The present study endeavors to lay a preliminary platform to understand the efficiency and efficacy of hydroxycinnamic acid derivatives in commonly used food sources.

Cytosolic protein delivery remains elusive. The instability of proteins in the endosomal/lysosomal environment and their inability to cross the endosomal membrane are two major bottlenecks. Here we explore the unique photothermal properties of gold nanorods (AuNRs) to trigger cytosolic delivery of proteins. Both partners, protein and AuNRs, are modified with a protease-resistant cell-penetrating peptide with nuclear targeting properties, to induce internalization. Once internalised, spatiotemporal control of protein release is securely achieved by near-infrared laser irradiation in the safe second biological window. Importantly, catalytic amounts of AuNRs are sufficient to trigger cytosolic protein delivery. To the best of our knowledge, this is the first time that AuNRs with their maximum of absorption in the second biological window are used to deliver proteins into the cytosol. This strategy represents a powerful tool for the intracellular delivery of virtually any class of protein.

Cancer is recognized as a worldwide public health concern. Therefore, there is a continuous quest to discover new effective medications with less side-effects. In recent years, researchers have shown an increased interest in medicinal plants as several plant species have shown promising biological activities. Thus, we seek to investigate three medicinal herbs that are commonly-found in the Middle Eastern region and yet have not been explored in depth including plants belonging to the Rhamnaceae, Polygonaceae, and Apocynaceae plant families. Initially, we investigated using three types of cancer cell lines for breast, colorectal, and liver cancers. We performed High Content Imaging (HCI)-Apoptosis Assay and ApoTox-Glo™ Triplex Assay on KAIMRC2 and HCT8 cell lines. The highest activity of HCI-Apoptosis Assay was with Calligonum comosum and Ziziphus nummularia in ethanol followed by Calotropis procera and Ziziphus nummularia in ethyl acetate. The IC₅₀ values for the families of Rhamnaceae, Polygonaceae, and Apocynaceae in HepG2 and HCT8 cell lines ranged from 0.089 to 9.84 mg/mL and 0.080 to 15.08 mg/mL, respectively. Further screening was conducted on an additional two cell lines namely the MDA-MB-231 and KAIMRC2 for selected seven extracts with the highest activity having IC₅₀ values ranged from 0.058 to 0.51 mg/mL and 0.029 to 0.19 mg/mL, respectively. Continuous scientific investigations to isolate and characterize the potent bioactive phytochemical(s) are warranted.

Antibiotics are compounds that can stop the reproduction or kill microorganisms, but for some reason, microorganisms in time show resistance to antibiotics. Using efflux pumps, the antibiotic entered into the bacterial cell is pumped out; therefore, it cannot act against bacteria. This situation increases antibiotic resistance in bacteria. Thus, microorganisms will develop multiple drug resistance against not only the antibiotic used but also many other antibiotics and rapidly spread to the environment. For this reason, antibiotic resistance has become a major problem all over the world, and new antibiotics and efflux pump inhibitor studies, which can affect these microorganisms that are resistant to multiple drugs are continuing rapidly. In this study, the behavior of 7 Escherichia coli, 1 Acinetobacter baumannii, 1 Enterococcus faecium, and 1 Klebsiella pneumoniae strains having active efflux pumps and developed multidrug resistance, against both fungal extracts and the current efflux pump inhibitor verapamil were investigated. In this study, the effects of some extracts in combination with antibiotics on MDR bacteria were investigated. The research was conducted using FTIR analysis. The FTIR results provided information about the mode of action of the extracts. According to the results of the FTIR analysis; in the extract - antibiotic combinations in which the inhibiting activities were seen, changes were observed mainly in fatty acids, proteins, carboxyl groups of free amino acids, polysaccharides, RNA/DNA, and also changes in the fingerprint region. It is important to carry out further studies in terms of confirming and expanding the data obtained.

The effective response of antibiotics is threatened by the proliferation of microorganisms that manifest resistance mechanisms, leading to an increase of progressively untreatable infectious diseases around the world. One solution to this problem could lie in shifting the strategy from searching for new antibacterials to discover new compounds that potentiate the antimicrobial activity of current antibiotics, therefore reverting resistance, through the interference with several mechanisms, including biofilm formation and efflux pumps (EPs). Using bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE) as a template, a macroalgae brominated bromophenol with antimicrobial activity, a series of 18 chalcone derivatives was prepared and evaluated for its antimicrobial activity and potential to fight antibiotic resistance. This includes seven chalcones, six dihydrochalcones and five diarylpropanes. Among them, two chalcones exhibited interesting antifungal activity and all compounds reversed resistance to vancomycin in the environmental isolate Enterococcus faecalis B3/101. Three compounds caused a four-fold decrease in the minimum inhibitory concentration (MIC) values of vancomycin against E. faecalis. All the dihydrochalcones and diarylpropanes displayed inhibition of EPs and biofilm formation in the tested multidrug resistant strain, suggesting that these compounds are EP inhibitors. Notably, dihydrochalcones and diarylpropanes did not show cytotoxicity in a mouse embryonic fibroblast cell line and they can potentially be regarded as hits for bacterial EPs inhibition.

Neutrophils play a crucial role in protection against intracellular pathogens such as viruses and mycobacteria but also in regulating systemic anaphylaxis or allergic skin reactions. Neutrophils intimately shape the adaptive immune response at various levels, including B cells, dendritic cells, and T cell populations. Significant attention in pharmacy is given to the search for natural substances that can affect the immune system and neutrophil function, with less adverse side effects. The phytoconstituents, such as polysaccharides, polyphenols, or terpenes, may serve as good candidates. Previously, we evaluated the anti-inflammatory activity of various plant extracts of the Iridaceae family, and identified extracts of Iris spp. rhizomes and Crocus sativum corms as promising anti-neutrophilic agents. The current study further extends the analysis of various groups of biologically active substances in extracts from Ukrainian plants. The tested samples include polysaccharide complexes of Crocus flowers and corms, Juno leaves and corms, Iris leaves and rhizomes, or Chamaenerion leaves; as well as water and ethanolic extracts Chamaenerion leaves. Using fMLF/CB-induced superoxide anion generation and elastase release assays in human neutrophils, C. angustifolium ethanolic (50%, vol/vol) and water extracts almost completely inhibited fMLF/CB-induced elastase release at 10 μg/mL (IC₅₀ 2.8-4.1 μg/mL). Interestingly, also Iris leaf polysaccharide extract inhibited elastase release by 39.0% (10 μg/mL), while C. angustifolium polysaccharides extract inhibited superoxide by 45.5% (10 μg/mL). This suggests that phenolic compounds may possess better activity in comparison to polysaccharides. The present study provided primary pharmacological evidence for anti-inflammatory agents from C. angustifolium.