Quantitative standardization of pharmacologically active components from antiplasmodial plant Solanum nudum Dunal (wild and in vitro)

Solanum nudum Dunal (Solanaceae) is most commonly known and used by the population of the colombian Pacific coast as an antimalarial treatment. This article study into optimization and quantitative analysis of compounds steroidal over time of development of this species when grown in vitro and wild. A new steroidal compound named SN6 was elucidated by NMR and a new method of quantification of seven steroidal compounds (Diosgenone DONA and six steroids SNs) using HPLC-DAD-MS in extracts of cultures in vitro and wild was investigated. Biology activity of extracts was found to a range of antiplasmodial activity in FCB2 and NF-54 with inhibitory concentration (IC50) between (17.04 -100 μg/mL) and cytotoxicity in U-937 of CC50 (7.18 -104.7 μg/mL). This method creates the basis for the detection of seven sterols antiplasmodial present in extracts from S. nudum plant as a quality parameter in the control and expression of phytochemicals.

Discovery of Novel Reductive Elimination Pathway for 10-Hydroxywarfarin

Coumadin (R/S-warfarin) anticoagulant therapy is highly efficacious in preventing the formation of blood clots; however, significant inter-individual variations in response risks over or under dosing resulting in adverse bleeding events or ineffective therapy, respectively. Levels of pharmacologically active forms of the drug and metabolites depend on a diversity of metabolic pathways. Cytochromes P450 play a major role in oxidizing R- and S-warfarin to 6-, 7-, 8-, 10-, and 4′-hydroxywarfarin, and warfarin alcohols form through a minor metabolic pathway involving reduction at the C11 position. We hypothesized that due to structural similarities with warfarin, hydroxywarfarins undergo reduction, possibly impacting their pharmacological activity and elimination. We modeled reduction reactions and carried out experimental steady-state reactions with human liver cytosol for conversion of rac-6-, 7-, 8-, 4′-hydroxywarfarin and 10-hydroxywarfarin isomers to the corresponding alcohols. The modeling correctly predicted the more efficient reduction of 10-hydroxywarfarin over warfarin but not the order of the remaining hydroxywarfarins. Experimental studies did not indicate any clear trends in the reduction for rac-hydroxywarfarins or 10-hydroxywarfarin into alcohol 1 and 2. The collective findings indicated the location of the hydroxyl group significantly impacted reduction selectivity among the hydroxywarfarins, as well as the specificity for the resulting metabolites. Based on studies with R- and S-7-hydroxywarfarin, we predicted that all hydroxywarfarin reductions are enantioselective toward R substrates and enantiospecific for S alcohol metabolites. CBR1 and to a lesser extent AKR1C3 reductases are responsible for those reactions. Due to the inefficiency of reactions, only reduction of 10-hydroxywarfarin is likely to be important in clearance of the metabolite. This pathway for 10-hydroxywarfarin may have clinical relevance as well given its anticoagulant activity and capacity to inhibit S-warfarin metabolism.

Keratinase Production by Endophytic Bacteria Aneurinibacillus aneurinilyticus VRCS-4 Isolated from Xerophytic Plant Opuntia ficus - indica (Prickly pear)

Bacterial endophytes colonize an ecological niche which is unexplored site makes them suitable to produce pharmacologically active substances with vast biotechnological potential therefore, xerophytes were chosen to isolate the endophytes. In the present study forty endophytic bacterial isolates were isolated from xerophytic plants grown near poultry farms and feather dumping sites. Of them eight isolates showed zone of hydrolysis and the maximum zone of hydrolyisis of 36mm was with VRCS-4 on skimmed milk agar. This isolate exhibited efficient feather degradation and was identified as Aneurinibacillus aneurinilyticus based on its morphological, biochemical test and molecular sequencing method. The isolate was deposited in NCBI with an accession number MW227423.The isolate showed maximum en-zyme activity of 140.24U/ml at 72h, pH 7.5 and 40º C at 140 rpm. Chicken feather 1% (w/v) used as a sole source of carbon and nitrogen. Feather deg-radation by A.aneurinilyticus VRCS-4 showed 90% degradation in feather meal broth. Ours appears to be the first report on keratinase production by endophytic bacteria from xerophytic plant (Opuntia ficus -indica).

In-silico activity prediction, structure-based drug design, molecular docking and pharmacokinetic studies of selected quinazoline derivatives for their antiproliferative activity against triple negative breast cancer (MDA-MB231) cell line

Background Cancer is a major health threat especially in unindustrialized nations. It surpasses coronary diseases and takes the number one killer position as a result of different global wide influences. Among many breast cancer substrates, triple-negative breast cancer (TNBC) is particularly devastating because it rapidly metastasize to other parts of the body, with a high risk of earlier recession and mortality. Result In this research work, four (4) quantitative structure activity relationship (QSAR) models were developed using a series of quinazoline derivatives with activities against triple negative breast cancer cell line (MDA-MB231), model 1 was selected due to its statistical fitness with the following validation parameters: R2 = 0.875, Q2 = 0.837, R2 − Q2 = 0.038, Next test set = 5, and R2ext = 0.655. Molecular docking studies was performed for the quinazoline series as well as the reference drug (Gefitinib) and the active site of the epidermal growth factor receptor (EGFR) (pdb id = 3ug2). Eight compounds (6, 10, 13, 16, 17, 18, 19 and 20) were observed to have better docking score docking scores relative to Gefitinib. Compound number nineteen from the training set (pred pIC50 = 5.67, Residual = − 0.04 and MolDock score = − 123.238) was identified as the best compound since it has the best Moldock score and was excellently predicted by the selected model with least residual value, Hence was adopted as template for the design of Ten (10) new novel compounds with better activities and better docking scores. The inhibitive activities of the designed compounds were predicted by the selected model and most of them possess an improved activity relative to the template compound (19). The designed compounds were also redocked on to active pocket of the EGFR receptor and it was observed that they displayed better docking scores compared to the Template and the reference drug (Gefitinib) utilized in the design. Furthermore, the designed compounds were subjected to ADMET and drug-likeness studies using SWISSADME and pkCSM online web tools and they were observed to be pharmacologically active, easily synthesized and do not violate the Lipinski’s rule of five. Conclusion Hence, the designed compounds can be employed as inhibitors of MDA-MB231 cell line after passing through in vivo and in vitro evaluation.

Recent Advances in the Application of Barbituric Acid Derivatives in Multicomponent Reactions

Barbituric acid is a pyrimidine heterocyclic organic compound, which is pharmacologically active. It is important to build structures containing various medicinal activities. This compound attracts the scientific research community in organic synthesis. It can be used in the synthesis of polyheterocyclic, natural, medicinal compounds, and organic sensors. Herein, the utilization of barbituric or thiobarbituric acid in multicomponent reactions is reported from 2016-2021 in this manuscript.

Pretreatment with 6-Gingerol Ameliorates Sepsis-Induced Immune Dysfunction by Regulating the Cytokine Balance and Reducing Lymphocyte Apoptosis

Sepsis is characterized by an initial net hyperinflammatory response, followed by a period of immunosuppression, termed immunoparalysis. During this immunosuppressive phase, patients may have difficulty eradicating invading pathogens and are susceptible to life-threatening secondary hospital-acquired infections. Due to progress in antimicrobial treatment and supportive care, most patients survive early sepsis. Mortality is more frequently attributed to subsequent secondary nosocomial infections and multiorgan system failure. 6-Gingerol is the major pharmacologically active component of ginger. Although it is known to exhibit a variety of biological activities, including anti-inflammation and antioxidation, the role of 6-gingerol in sepsis-induced immune dysfunction remains elusive. Thus, we investigated whether 6-gingerol improves septic host response to infections during sepsis. 6-Gingerol-treated mice showed significantly lower mortality in polymicrobial sepsis induced by cecal ligation and puncture LPS via enhanced bacterial clearance in the peritoneum, blood, and organs (liver, spleen, and kidney) and inhibited the production of TNF-α and IL-6 in TLR2 and/or TLR4-stimulated macrophages. In addition, we demonstrated that survival improvement of secondary infection following septic insult was associated with an initial response of enhanced neutrophil numbers and function at the infection site, reduced apoptosis of immune cells, and a shift from a T helper cell type 2 (Th2) to a T helper cell type 1 (Th1) cytokine balance in the hypoinflammation phase. Our overall findings suggest that 6-gingerol potentially restores sepsis-induced immune dysfunction by shifting the balance of Th1/Th2 and by regulating apoptosis of immune cells.

Using high performance thin layer chromatography for the detection of pharmacologically active secondary metabolites in Empetrum nigrum L.

Introduction. The article presents the results of the detection of pharmacologically active secondary metabolites in black crowberry Empetrum nigrum L. using the method of high performance thin layer chromatography (HPTLC).Aim. To show the efficiency of HPTLC for conducting preliminary phytochemical analysis to determine the main groups of metabolites in promising medicinal plant species.Materials and methods. HPTLC analysis was carried out on a CAMAG device (Switzerland), using MERCK HPTLC silica gel 60 F154, 20 × 10 cm plates. For the evaporation of the samples, a Heidolph vacuum rotary evaporator (Germany) was used. The aerial parts (shoots) of Empetrum nigrum were harvested next to St. Petersburg State Chemical and Pharmaceutical University (SPCPU) nursery garden of medicinal plants (Leningrad Region, Vsevolozhsky District, Priozerskoe Highway, 38 km) in August 2019.Results and discussion. In the course of the research, four fractions from the aerial parts of Empetrum nigrum were obtained: hexane, dichloromethane, butanol, and water. Then, these fractions were investigated by HPTLC in two solvent systems – n-butanol : acetic acid : water (BAW) (4 : 1 : 2) and hexane : dichloromethane : methanol (HDM) (1 : 2 : 0.5). After scanning densitometric analysis of the plates eluted in the HDM system, it was revealed, that the hexane and dichloromethane fractions have a similar composition and contain the greatest amount of compounds, compared to the butanol and water fractions, and in the BAW system, it was found, that the butanol fraction contains the greatest variety of metabolites. As a result of UV spectroscopy, it was found, that the main groups of compounds contained in the hexane and dichloromethane fractions are derivatives of chalcones, dihydrochalcones, bibenzyls and 9,10-dihydrophenanthrenes. While in the butanol fraction, the main groups of secondary metabolites were derivatives of flavonoids and tanninsConclusion. The data obtained allow us to note the efficiency, speed and simplicity of HPTLC for conducting preliminary phytochemical analysis to determine the main groups of metabolites of promising medicinal plant species.

Bacterial Nanocellulose Fortified with Antimicrobial and Anti-Inflammatory Natural Products from Chelidonium majus Plant Cell Cultures

In this work we developed a bi-functional Bacterial-Nano-Cellulose (BNC) carrier system for cell cultures of Chelidonium majus—a medicinal plant producing antimicrobial compounds. The porous BNC was biosynthesized for 3, 5 or 7 days by the non-pathogenic Komagataeibacter xylinus bacteria and used in three forms: (1) Without removal of K. xylinus cells, (2) partially cleaned up from the remaining K. xylinus cells using water washing and (3) fully purified with NaOH leaving no bacterial cells remains. The suspended C. majus cells were inoculated on the BNC pieces in liquid medium and the functionalized BNC was harvested and subjected to scanning electron microscopy observation and analyzed for the content of C. majus metabolites as well as to antimicrobial assays and tested for potential proinflammatory irritating activity in human neutrophils. The highest content and the most complex composition of pharmacologically active substances was found in 3-day-old, unpurified BNC, which was tested for its bioactivity. The assays based on the IL-1β, IL-8 and TNF-α secretion in an in vitro model showed an anti-inflammatory effect of this particular biomatrix. Moreover, 3-day-old-BNC displayed antimicrobial and antibiofilm activity against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. The results of the research indicated a possible application of such modified composites, against microbial pathogens, especially in local surface infections, where plant metabolite-enriched BNC may be used as the occlusive dressing.