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A series of new 2-amino-7-hydroxy-8-methyl-4-aryl-4H-chromene-3-carbonitrile derivatives (4a-4g) have been synthesized by a one-pot multicomponent reaction of 2-methylresorcinol (1) and malononitrile (2) with various aldehydes (3). All the synthesised compounds (4a-4g) have been characterised using FT-IR, 1H NMR, 13C NMR, HR-MS and evaluated for swarming behaviour, biofilm formation, biofilm disruption and urease activity against P. mirabilis (MTCC-425). Among all the synthesized compounds, compounds 4a, 4b and 4g showed slightly inhibited swarming behaviour and compounds 4f and 4g inhibited biofilm formation with increasing concentration. SEM (Scanning Electron Microscope) imaging shows that compound 4e effectively disrupts the preformed biofilm. Also, compounds 4d and 4e showed 40% reduction in urease activity. The SAR studies of synthesized compounds are elaborated in detail to provide key structural features. Furthermore, molecular docking studies against urease could provide a mechanistic basis for the inhibition. The per-residue interaction analysis suggested the involvement of non-bonded and bonded interactions with the active site of urease. Hence, the aim of the below study was to synthesize new chromene derivatives and study their biological activities. [ABSTRACT FROM AUTHOR]

Betulinic acid (BA) was used as starting building block to create a library of novel BA-derived compounds containing O- and N-heterocycles. Firstly, BA was converted into methyl betulonate (BoOMe), which was used as intermediate in the developed methodologies. 1,2-Oxazine-fused BoOMe compounds were obtained in 12–25% global yields through a Michael addition of nitromethane to methyl (E)-2-benzylidenebetulonate derivatives, followed by nitro group reduction and intramolecular cyclization. Remarkably, the triterpene acts as a diastereoselective inducer in the conjugate addition of nitromethane, originating only one diastereomer out of four possible ones. Furthermore, other oxygen and nitrogen-containing heterocycles were installed at the A-ring of BoOMe, affording 2-amino-3-cyano-4H-pyran-fused BoOMe, diarylpyridine-fused BoOMe and 1,2,3-triazole–BoOMe compounds, using simple and straightforward synthetic methodologies. Finally, BA was revealed to be a versatile starting material, allowing the creation of a molecular diversification of compounds containing a triterpenic scaffold and O- and N-heterocycles. [ABSTRACT FROM AUTHOR]

Supporting cells of oocytes, i.e., cumulus cells, control oocyte quality, which determines fertilization success. Therefore, the transformation of mature and immature cumulus cells (MCCs and ICCs, respectively) into dysmature cumulus cells (DCCs) with dead characteristics deteriorates oocyte quality. However, the molecular basis for this transformation remains unclear. Here, we explored the link between autophagic decline and cumulus transformation using cumulus cells from patients with infertility, female mice, and human granulosa cell-derived KGN cell lines. When human cumulus cells were labeled with LysoTracker probes, fluorescence corresponding to lysosomes was enhanced in DCCs compared to that in MCCs and ICCs. Similarly, treatment with the autophagy inhibitor chloroquine elevated LysoTracker fluorescence in both mouse cumulus cells and KGN cells, subsequently suppressing ovulation in female mice. Electron microscopy analysis revealed the proliferation of abnormal lysosomes in chloroquine-treated KGN cells. Conversely, the addition of an autophagy inducer, trehalose, suppressed chloroquine-driven problematic lysosomal anomalies and ameliorated ovulation problems. Our results suggest that autophagy maintains the healthy state of the supporting cells of human oocytes by suppressing the formation of lysosomes. Thus, our results provide insights into the therapeutic effects of trehalose on female fertility. [ABSTRACT FROM AUTHOR]

Astraeus hygrometricus extensively been utilized by tribal people for long time. A triterpene, astrakurkurol has been isolated from A. hygrometricus but anticancer effect of this novel triterpene has imperceptibly been investigated. Motive of this research was to scrutinize its underlying apoptotic mechanism in HepG2 cells. Cytotoxicity studies demonstrated a selective effect of astrakurkurol with towering influence in HepG2 than Thle2 cells. The exposure of these triterpene‐induced marked apoptotic morphological changes enhanced the rate of cell apoptosis and arrest cell cycle at G0/G1. Furthermore, these results are aided by decline in the expression of Bcl‐2, Bcl‐xL with an increase in the expression of p53, Bax, Fas, FADD together with the activation of caspase cascade. Astrakurkurol also displayed a remarkable anti‐migratory capacity at a lower concentration. Altogether, studies explained anti‐proliferative, pro‐apoptotic, and anti‐migratory efficacy of astrakurkurol on HepG2, composing a gripping challenge in the advancement of novel treatments against hepatocellular carcinoma. Practical applications: Mushrooms, the minuscule pharmaceutical factory, bear hundreds of novel elements with incredible biological attributes. Triterpenoids from mushrooms has been proven to bear potentials of curing cancer. This study highlights the cytotoxic and anti‐migratory effects of novel triterpene in vitro in HepG2 cell, an HCC cell line. Astrakurkurol mediated cell death via both extrinsic and intrinsic apoptotic signaling. Utilization of astrakurkurol will provide a non‐toxic substitute of chemotherapy and also uplift the value of forsaken taxon, Astraeus and boost the rural acceptance. [ABSTRACT FROM AUTHOR]

Much attention is given to research and development of efficient systems for the delivery of essential omega-3-polyunsaturated fatty acids and other nutraceuticals to the human body with food. Nanocomplexes, which are based on soybean phosphatidylcholine liposomes with nutraceuticals included, are among the efficient delivery systems. The prolonged use of these nanocomplexes may affect the antioxidant status in various organs and tissues. In this work, thermo-initiated chemiluminescence was used to study changes in the antioxidant activity of the blood plasma, liver, and brain lipids in mice divided into six groups depending on the composition of liposomal nanocomplexes introduced into drinks substituted for water in a long-term (3 month) diet. The components of six types of liposomal nanocomplexes, except for phosphatidylcholine, in different combinations were clove essential oil, fish oil, and sodium caseinate. The results of the study showed that nanocomplexes containing liposomes made of phosphatidylcholine with the addition of fish oil and clove essential oil and encapsulated in milk protein (sodium caseinate) proved to be the most effective in increasing the antioxidant activity of the blood plasma and brain lipids in mice compared to the control. [ABSTRACT FROM AUTHOR]

2‐[(4‐Thiazolylmethyl)thio]‐1H‐benzimidazole 3 was prepared and was allowed to react with ethyl chloroactate then with hydrazine hydrate to afford the hydrazide derivative 5, which was then reacted with aromatic aldehydes to afford the corresponding arylidine derivatives 6–9. Heterocyclization of the latter hydrazones with acetic anhydride afforded the substituted 1,3,4‐oxadiazoline derivatives 10–13. In addition, new ((thiazolyl)imidazolyl) oxadiazole thioglycoside and acyclic‐C nucleoside analog were prepared via heterocylization of the hydrazide 5 then glycosylation with α‐acetobromoglucose or condensation with D‐xylose, respectively. All the new compounds were structurally characterized. The anticancer activity of some of the newly synthesized compounds was studied against human breast cancer cells (MCF‐7). The results of the anticancer activity showed that compounds 8, 11, 12, 17, and 18 revealed high activities superior to Doxorubicin; however, the other derivatives showed moderate to low inhibition activities against human breast cancer cells. Docking studies into CDK2 enzyme were investigated, which supported the anticancer activity results. [ABSTRACT FROM AUTHOR]

Chromone derived carbazones provide an important antioxidant activity by exhibiting radical scavenging action, Semicarbazones are synthesized in good yield and these act as a good radical scavenger, where the presence of various substituent at C-6 of chromone nucleus tend to alter the activity behaviour, presence of electronegative atom such as fluoro/ chloro enhances the radical scavenging activity in comparison to electron donating group. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a multifactorial and chronic disease describing the destruction of cartilage that can lead to defects in the elderly. There is currently no practical strategy that can reverse the OA process. Here, we describe nepetin, a small natural compound with extracellular matrix (ECM) and inflammation regulating functions. In this study, we investigated the therapeutic effects of nepetin on interleukin-1β (IL-1β)-induced inflammation in mice chondrocyte and OA model. In chondrocytes, treatment with nepetin inhibited the overexpression of pro-inflammatory cytokines and mediators induced by IL-1β. Moreover, pretreatment or posttreatment with nepetin also reduced the ECM catabolism and enhanced the ECM anabolism. Mechanistically, nepetin suppressed NF-κB signaling pathway in IL-1β stimulated chondrocyte. Meanwhile, our molecular docking studies indicated nepetin had a powerful binding capacity to p65. Furthermore, nepetin showed a protective and therapeutic effect on the mouse OA model. To sum up, this study indicated nepetin had a new potential therapeutic option in OA., (© 2021 Wiley Periodicals LLC.)

The current study was conducted to evaluate the antiproliferative and oxidative damage protection potential of endophytic fungi Aspergillus fumigatus and Chaetomium globosum isolated from Moringa oleifera. The chloroformic extract (CE) of both the fungi showed dose dependent antiproliferative activity against human prostate adenocarcinoma (PC-3) cell line with (IC 50 ) value of 0.055 mg/ml and 0.008 mg/ml, respectively. Further, CE of both the fungi was studied for their ability to induce apoptosis in PC-3 cell line. Various deformities in the cancerous cells treated with CE of both the fungi have been observed by confocal microscopy which indicates the cell death by apoptosis. Further apoptosis inducing ability of CE of both the fungi was observed using various flow cytometric studies. The chloroformic extract of both the fungi showed slight increase in the level of reactive oxygen species to induce apoptosis. It also showed arrest of cancerous cells at G0/G1 phase of cell cycle to induce apoptosis. The externalization of phosphatidylserine (PS) to induce apoptosis was also observed when analysed using Annexin V-FITC/PI double staining assay where the CE of A. fumigatus and C. globosum showed the total apoptosis of 94.2% and 90.3%, respectively, at the highest tested concentration of GI 70 . The CE of both the fungi further showed the protective behaviour for plasmid DNA pBR322, when tested for their effect against the oxidative stress caused by the Fenton's reagent. Thus, the studies demonstrated a good antiproliferative and oxidative damage protection potential of the endophytic fungi., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A new fabrication of {[H3O][Cu6(tpta)3(DMA)4(COO)]·12H2O·7DMA} (1) was used as a drug vehicle of 5-fluorouracil (5-FU) for drug delivery. The incorporation of the drug 5-FU into the 1 was around 47.3 wt% per gram of dehydrated 1. Cargo release behavior and material degradation profile were also investigated under different mdeium. 5-FU is released in a highly controlled and progressive manner with 92% of the drug release after 96 h at acidic condition and with 88% after 96 h at PBS. In vitro cytotoxicity assays indicated that the 1 possesses no obvious cytotoxicity. The results provide a new avenue for MOFs to be used as potential drug delivery. [ABSTRACT FROM AUTHOR]

We compared the effects of the dipeptide carnosine on learning and the biochemical parameters in the brain of rats trained for defensive and food-procuring conditioned reflexes. In the first series, the animals were trained for active avoidance behavior; in the second series, the rats were trained for the food-procuring conditioned reflex in a modified shuttle box. After training, the hypothalamus and cortex were dissected and used for evaluation of lipid peroxidation processes and the levels of monoamine neurotransmitters. The activating effect of carnosine was observed during the entire training period of defensive training, whereas during training for the food-procuring reflex it was observed only in the first two sessions. In both training series, impairments of oxidative homeostasis were found in the brain; these were efficiently corrected with carnosine. This effect of carnosine may explain its positive influence on learning. Moreover, in both models, carnosine increased the contents of the main monoamine neurotransmitters in the hypothalamus. These data led us to the conclusion about high prospectivity of further studies of the carnosine modulatory effects in the nervous system. [ABSTRACT FROM AUTHOR]

The catalytic efficiency of a bifunctional chiral thiourea derived from L-proline was evaluated in the asymmetric direct vinylogous Michael reaction of α,α-dicyanoolefins to β-nitrostyrenes with an electron- releasing or electron-withdrawing substituent in various positions. The corresponding adducts were isolated in good yields, with excellent diastereo- (>99%) and enantioselectivity (up to 95%). The Michael adducts were further functionalized to achieve the synthesis of polycyclic fused pyrrolidines with three contiguous stereocenters in good enantioselectivities. [ABSTRACT FROM AUTHOR]

This work describes the development and optimization of an analytical method utilizing liquid chromatography and chemometrics to evaluate and differentiate two varieties of Casearia sylvestris Swartz (Salicaceae) from São Paulo State (Brazil) based on their secondary metabolite profiles. Previously, analytical studies only concerned the analysis of clerodane-type diterpenes. Therefore, considering the importance of including phenolic compounds in such analysis, we used design of experiments to simultaneously extract and detect the largest number of compounds from both chemical classes. This new strategy allowed a comprehensive chromatographic analysis of C. sylvestris, and the results for the two varieties exhibited an interesting distribution according to their original ecosystems, suggesting a strong correlation to the main metabolites found in each species group. Besides their inherent morphological differences, C. sylvestris variety lingua, mainly found in Cerrado areas, predominantly contains phenolic compounds, while C. sylvestris variety sylvestris, mainly found in Atlantic Forest areas, contains mostly clerodane-type diterpenes. Finally, it was also possible to observe differences in the secondary metabolite composition within each group depending on the place where samples were collected. [ABSTRACT FROM AUTHOR]

Anxiety and insomnia are among the most common mental health disorders and are a major cause of disability around the world. Traditional herbal medicines are receiving significant attention in global health debates. Several Italian regions maintain rural traditions and are among the most extensively studied areas of Europe regarding medicinal plant uses. The present overview aims to highlight the use of wild and cultivated plants, specifically as sedatives and for insomnia treatment in Italy, and to collect, analyze, and summarize the available literature about their pharmacological activity as well as clinical and pre-clinical studies concerning the most cited plants. In total, 106 wild taxa are used in Italy for sedative purposes. The plant species belong to 76 genera and 32 families, of which the most cited are Asteraceae (24.2%) and Lamiaceae (21.1%). Leaves (29%) and flowers (27%) are the plant parts mostly used as infusion (70%) and decoction (25%). Out of 106 taxa documented, only the most cited are analyzed in this overview (A. arvensis L., C. nepeta L., C. monogyna Jacq., H. lupulus L., L. nobilis L., L. angustifolia Mill., M. sylvestris L., M. chamomilla L., M. officinalis L., O. basilicum L., P. rhoeas L., P. somniferum L., R. officinalis L., T. platyphyllus Scop., and V. officinalis L.). Among the fifteen species selected, only seven have been studied for their pharmacological activity as hypnotic-sedatives. Future pre-clinical and clinical studies are needed to better clarify the mechanism of action of bioactive compounds and confirm the potential of these alternative therapies. [ABSTRACT FROM AUTHOR]