Abstract

In our search for peroxisome proliferator-activated receptor (PPAR) agonists, five undescribed compounds, namely two acyclic diterpenes (1 and 2; cladopsol A and cladopsol B), two sesquiterpenes (3 and 4; cladopsol C and cladopsol D), and one C21-ecdysteroid (5; cladopsol E), and 15 known compounds were isolated from the jellyfish-derived fungus – Cladosporium oxysporum. The structures of the undescribed compounds were defined using UV, NMR, HR-ESI-MS, and electronic circular dichroism (ECD) spectroscopy and a modified Mosher's method. Luciferase reporter assay and docking analysis suggested that cladopsol B may function as a PPAR-γ partial agonist with a potential antidiabetic lead which may evade the side effects of full agonists. Moreover, cladopsol B stimulated glucose uptake in HepG2 cells with an efficacy comparable to that of rosiglitazone, but with less side effect induced by lipid accumulation in 3T3-L1 cells. Therefore, cladopsol B could serve as a molecular skeleton in a study of advanced antidiabetic lead with less side effect.

Abstract

In the last few years, the interest in sulfonamides has expanded owing to their broad spectrum of biological activities. Their flexible structure turns them into amazing candidates to replace old drugs or develop modern multi-target agents. In this study, a series of new sulfonamides (sul1-5) was evaluated, in vitro, for the antibacterial, cytotoxic and genotoxic effects. The antibacterial activity was investigated against 12 clinical and 4 reference strains. Cytotoxic activity was carried out by the brine shrimp bioassay and the genotoxicity was assessed in the Ames test. An interesting antibacterial activity was showed especially against Gram negative strains. The inhibition zones varied between 15 and 30 mm, and the Minimum Inhibitory Concentrations (MIC's) values between 0.5 and 256 μg/ml. No antibacterial activity was shown with S. aureus isolates. Only Sul1 and Sul4 were active against P. aeruginosa. Compounds Sul1 and Sul2 showed a significant cytotoxicity with LC₅₀ equal to 18.29 and 18 μg/ml respectively, and a genotoxic effect against TA100 and TA1535 Salmonella strains. Only compounds Sul3, Sul4 and Sul5 with an interesting antibacterial activity, no cytotoxicity and no genotoxic effects, could be exploited against resistant pathogens as new drugs.

Abstract

In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner.

Abstract

In this study, it was aimed to examine the capacity of deep eutectic solvents (DESs) with different contents to extract bioactive compounds from tarragon (Artemisia dracunculus L.) plant. For this reason, the total phenolic-flavonoid content, total proanthocyanidin content and antioxidant/antimicrobial activities of the prepared DES extracts were investigated, as well as the individual phenolic and individual amino acid profiles. According to the results, DES10 had the highest efficiency in terms of its capacity to extract individual phenolics (approximately 59 mg/100 g) and individual amino acids (approximately 2500 mg/kg), and also gave a higher yield compared to ethanol (approximately 44 mg/100 g for individual phenolics and about 19810 mg/kg for individual amino acids) and methanol (approximately 58 mg/100 g for individual phenolics and approximately 21430 mg/kg for individual amino acids). However, the total phenolic content, total flavonoid content and antioxidant activity values of DES extracts were determined between 59.09–77.50 mg GAE/100 g, 28.68–45.55 mg GAE/100 g and 42.96–146.86 mg TE/100 g, respectively. Therefore, it can be recommended to use these green solvents, which are known as environmentally friendly, as an alternative to organic solvents in the process of preparing extracts of this important medicinal plant in different areas.

Abstract

Gagea genus, which is native to the Mediterranean and Black Sea regions, has attracted significant attention due to its biodiversity and potential health benefits. In this study, the biochemical composition and biological activities of methanol extracts from various parts of G. taurica were investigated, along with their anatomical and morphological characteristics. The best antimicrobial activity was found to be MeOH extracts of corm and leaf against several Candida strains with MIC=640 μg/mL. The highest level of phenolics together with significant results of antioxidant activities were observed in flowers extracts. The α-amylase inhibition assay results showed that the highest inhibition percentage was observed with acarbose (59 %), followed by leaf extract (43 %). Leaf exhibited the most effective inhibitory activity in AChE inhibition assay, whereas flower demonstrated the most significant inhibitory activity in BChE inhibition assay. Hesperidin was found as 1621.0001 ng/ml value in flower extract and 283.9339 ng/ml value leaf.

Abstract

The current study aimed to evaluate the anti-inflammatory activity of Dicliptera bupleuroides Nees aerial parts methanol extract and its different fractions namely hexane, chloroform, ethyl acetate and butanol in vitro using cyclooxygenase inhibitory assay (COX-2). In vivo anti-inflammatory evaluation was performed using carrageenan and formalin induced inflammation in rat models followed by molecular docking. High performance liquid chromatography (HPLC) and gas chromatography coupled with mass chromatography (GC/MS) analyses were used for chemical analyses of the tested samples. The tested samples showed significant inhibition in COX-2 inhibitory assay where methanol extract (DBM) showed the highest inhibitory potential at 100 μg/mL estimated by 67.86 %. At a dose of 400 mg/kg, all of the examined samples showed pronounced results in carrageenan induced acute inflammation in rat model at 4^th h interval with DBM showed the highest efficiency displaying 65.32 % inhibition as compared to the untreated rats. Formalin model was employed for seven days and DBM exhibited 65.33 % and 69.39 % inhibition at 200 and 400 mg/kg, respectively approaching that of the standard on the 7^th day. HPLC revealed the presence of caffeic acid, gallic acid and sinapic acid, quercetin and myricetin in DBM. GC/MS analysis of its hexane fraction revealed the presence of 16 compounds belonging mainly to fatty acids and sterols that account for 85.26 % of the total detected compounds. Molecular docking showed that hexadecanoic acid followed by decanedioic acid and isopropyl myristate showed the best fitting within cyclooxygenase-II (COX-II) while nonacosane followed by hexatriacontane and isopropyl myristate revealed the most pronounced fitting within the 5-lipoxygenase (5-LOX) active sites. Absorption, metabolism, distribution and excretion and toxicity prediction (ADMET/ TOPKAT) concluded that most of the detected compounds showed reasonable pharmacokinetic, pharmacodynamic and toxicity properties that could be further modified to be more suitable for incorporation in pharmaceutical dosage forms combating inflammation and its undesirable consequences.

Abstract

Curcumin has antioxidant properties resulting from its radical scavenging ability and inhibition of inflammation-associated factors. However, its lack of solubility, instability, and poor bioavailability are impediments to its therapeutic use. As potential alternatives, we synthesized and performed chemical analysis of thirty diarylidene-N-methyl-4-piperidone (DANMP), diheteroarylidene-N-methyl-4-piperidone (DHANMP), and spirobibenzopyran (SBP) derivatives, one of which was also characterized by single crystal X-ray diffraction. All compounds were evaluated for antioxidant activity via 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and for drug-like properties in silico. A subset of five compounds was investigated in terms of aqueous solubilities, which were significantly improved compared to that of curcumin. In vitro assessments of cellular and anti-inflammatory effects were conducted via real time polymerase chain reaction (RT-PCR) and Griess assays to evaluate the presence of inflammatory/activated (M1) markers and production of nitric oxide (NO) species, which are associated with inflammation. The five compounds reduced levels of markers and NO to extents similar to or better than curcumin in inflamed cells, and showed no adverse effects on cell viability. We show that these compounds possess anti-inflammatory properties and may be used as curcumin-substitutes with improved characteristics.

Abstract

This study, it was aimed to examine the change in the antimicrobial effect of sea anemone Parazoanthus axinellae extract by forming its nanoflowers. A scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDX) were expended to observe the morphologies of the Cu NFs that had been produced. Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) techniques were expended to analyze the managing assemblies in P. axinellae extract, which perform an effective part in the synthesis routine, as well as the crystal assembly of NFs.

P. axinellae extract mediated the HNFs (Hybrid nanoflowers) are at high, pure crystalline nature, flower shape with a crystallographic system at the nanoscale with mean crystallite size 21.9 nm using XRD, and average particle size ~10 nm by SEM. The broad absorption band at 2981–2915 cm⁻¹ in the FT-IR spectra of anemone extract and Cu-anemone NFs represents the unique peak of hydroxy groups.

In addition, Cu NFs were tested for their antibacterial properties. Cu NFs have been discovered to exhibit antibacterial properties. It is suggested that P. axinellae extract and various inorganic components be used to synthesize a variety of NFs and assess their suitability for usage in biomedical fields.

Abstract

To develop novel antimicrobial agents a series of 2(4)-hydrazone derivatives of quinoline were designed, synthesized and tested. QSAR models of the antibacterial activity of quinoline derivatives were developed by the OCHEM web platform using different machine learning methods. A virtual set of quinoline derivatives was verified with a previously published classification model of anti-E. coli activity and screened using the regression model of anti-S. aureus activity. Selected and synthesized 2(4)-hydrazone derivatives of quinoline exhibited antibacterial activity against the standard and antibiotic-resistant S. aureus and E. coli strains in the range from 15 to 30 mm by the diameter of growth inhibition zones. Molecular docking showed the complex formation of the studied compounds into the catalytic domain of dihydrofolate reductase with an estimated binding affinity from −8.4 to −9.4 kcal/mol.

Abstract

In this study, lemon peels were used as volatile component source. Automatic solvent extraction has been used for the recovery of limonene rich citrus volatile extract for the first time. The process parameters (amount of raw material, immersion time and washing time) were analyzed to optimize the process by means of Box-Behnken design via response surface methodology. The optimum conditions were achieved by ~10 g fresh lemon peel, and ~15 min immersion time and ~13 min washing time. The difference between the actual (89.37 mg/g limonene) and predicted (90.85 mg/g limonene) results was satisfactory (<2 %). α-Terpinene, β-pinene, citral, ɣ-terpinene and linalool were determined as other major volatiles in the peel extract. FT-IR and ¹H- and ¹³C-NMR spectroscopies were applied to verify the identified volatile compounds.