On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

Several valuable biologically active molecules can be obtained through C–H activation processes. However, the use of expensive and not readily accessible catalysts complicates the process of pharmacological application of these compounds. A plausible way to overcome this issue is developing and using cheaper, more accessible, and equally effective catalysts. First-row transition (3d) metals have shown to be important catalysts in this matter. This review summarizes the use of 3d metal catalysts in C–H activation processes to obtain potentially (or proved) biologically active compounds.

Potential Implications of Quercetin in Autoimmune Diseases

Autoimmune diseases are a worldwide health problem with growing rates of morbidity, and are characterized by breakdown and dysregulation of the immune system. Although their etiology and pathogenesis remain unclear, the application of dietary supplements is gradually increasing in patients with autoimmune diseases, mainly due to their positive effects, relatively safety, and low cost. Quercetin is a natural flavonoid that is widely present in fruits, herbs, and vegetables. It has been shown to have a wide range of beneficial effects and biological activities, including anti-inflammation, anti-oxidation, and neuroprotection. In several recent studies quercetin has reportedly attenuated rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and systemic lupus erythematosus in humans or animal models. This review summarizes the evidence for the pharmacological application of quercetin for autoimmune diseases, which supports the view that quercetin may be useful for their prevention and treatment.

Synthesis, Characterization and Antimicrobial Evaluation of Mannich Bases of 4-(Furan-2-yl-methyleneamino)-3-(2-hydroxyphenyl)-1H-1,2,4-triazole-5-thione

Triazole nucleus has drawn much attention since the last decade because of its various potent biological activities. The pharmacological application of triazoles has been widely recognized and well documented. Schiff and Mannich bases are both considered as bioactive compounds, however, there are not much of documentation about the Mannich bases as their study has begun lately. The main aim of this study was to synthesize new Mannich bases from Schiff base bearing 1,2,4-triazole nucleus to access their antimicrobial activities. The newly synthesized compounds 1,2,4-triazole-5-thione, Schiff base (4) and Mannich bases (5a & 5b) were characterized by spectral techniques like UV, FT-IR, and NMR. Mannich bases were tested against various bacterial (gm +ve and gm –ve) as well as fungal strains. The synthesized Mannich bases showed good to moderate activities against the tested bacterial and fungal strains.

Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise

Growing evidence supports that pharmacological application of growth differentiation factor 15 (GDF15) suppresses appetite but also promotes sickness-like behaviors in rodents via GDNF family receptor α-like (GFRAL)-dependent mechanisms. Conversely, the endogenous regulation of GDF15 and its physiological effects on energy homeostasis and behavior remain elusive. Here we show, in four independent human studies that prolonged endurance exercise increases circulating GDF15 to levels otherwise only observed in pathophysiological conditions. This exercise-induced increase can be recapitulated in mice and is accompanied by increased Gdf15 expression in the liver, skeletal muscle, and heart muscle. However, whereas pharmacological GDF15 inhibits appetite and suppresses voluntary running activity via GFRAL, the physiological induction of GDF15 by exercise does not. In summary, exercise-induced circulating GDF15 correlates with the duration of endurance exercise. Yet, higher GDF15 levels after exercise are not sufficient to evoke canonical pharmacological GDF15 effects on appetite or responsible for diminishing exercise motivation.

Medicinal and Biological Significance of Phenoxazine Derivatives

: Since 1887, phenoxazine derivatives have attracted attention of chemist due to its versatile utility, industrially and pharmacologically. Literature is found abundant with various pharmacological activities of phenoxazine derivatives like antitumor, anticancer, antifungal, antibacterial, anti-inflammatory, anti-diabetic, anti-viral, anti-malarial, antidepressant, analgesic and many other drug resistance reversal activities. This review covers detailed over-view on pharmacological application of phenoxazine nucleus, its chemistry and reactivity and also illustrating the incorporation of different group at different positions enhancing its biological application, besides some synthetic procedures.

Entomopathogenic Filamentous Fungi as Biocatalysts in Glycosylation of Methylflavonoids

Flavonoids are known for their numerous biological activities; however, their pharmacological application is limited by poor bioavailability. Glycosides are usually more stable and more soluble in water and in this form, flavonoids are present in nature. Likewise, the presence of the methyl group in the flavonoid skeleton results in facilitated absorption and greater bioavailability. Entomopathogenic filamentous fungi are effective in the biotransformation of flavonoids; they are known especially for efficient glycosylation. In the current study we used strains of Beauveria bassiana KCH J1.5 and Isaria fumosorosea KCH J2 to biotransform flavonoids with a single methyl group. 2′-Hydroxy-5′-methylchalcone was biotransformed by both strains into 2′-hydroxy-5′-methylchalcone 3-O-β-D-(4″-O-methyl)-glucopyranoside. In the culture of B. bassiana KCH J1.5 four products were obtained from 6-methylflavanone: 4′-hydroxy-6-methylflavanone 3′-O-β-D-(4″-O-methyl)-glucopyranoside; 4′-hydroxyflavanone 6-methylene-O-β-D-(4″-O-methyl)-glucopyranoside; 6-hydroxymethylflavanone 3′-O-β-D-(4″-O-methyl)-glucopyranoside and 4′-hydroxy-6-hydroxymethylflavanone 3′-O-β-D-(4″-O-methyl)-glucopyranoside. Biotransformation with I. fumosorosea KCH J2 as a biocatalyst resulted in the formation of 6-methylflavanone 4′-O-β-D-(4″-O-methyl)-glucopyranoside and 2-phenyl-6-methylchromane 4-O-β-D-(4″-O-methyl)-glucopyranoside. All of these flavonoids can be used in biological activity tests and can be useful in studies concerning structure—bioactivity relationships.

Biodiversity of β-Carboline Profile of Banisteriopsis caapi and Ayahuasca, a Plant and a Brew with Neuropharmacological Potential

Ayahuasca is a psychoactive infusion with a large pharmacological application normally prepared with Banisteriopsis caapi, which contains the monoamine oxidase inhibitors β-carbolines, and Psichotria virids, which contains the serotonin receptor agonist N,N dimethyltryptamine (DMT). The objectives of this study were to investigate the chemical profile of B. caapi and of ayahuasca collected in various Brazilian regions. In total, 176 plant lianas, of which 159 B. caapi and 33 ayahuasca samples were analyzed. Dried liana samples were powdered, extracted with methanol, diluted, and analyzed by LC-MS/MS. Ayahuasca samples were diluted and analyzed. Mean concentrations in B. caapi were 4.79 mg/g harmine, 0.451 mg/g harmaline, and 2.18 mg/g tetrahydroharmine (THH), with a high variability among the samples (RSD from 78.9 to 170%). Native B. caapi samples showed significantly higher harmine concentrations than cultivated ones, and samples from the Federal District/Goiás had higher THH content than those collected in the State of Acre. The other Malpighiaceae samples did not contain β-carbolines, except for one D. pubipetala sample. Concentrations in ayahuasca samples ranged from 0.109 to 7.11 mg/mL harmine, 0.012 to 0.945 mg/mL harmaline, 0.09 to 3.05 mg/mL THH, and 0.10 to 3.12 mg/mL DMT. The analysis of paired ayahuasca/B. caapi confirmed that harmine is reduced to harmaline and to THH during the brew preparation. This is the largest study conducted with Malpighiaceae samples and showed a large variability in the main β-carbolines present in B. caapi. This biodiversity is a challenge for standardization of the material used in ethnopharmacological studies of B. caapi and ayahuasca.

Self-Nanoemulsifying Drug Delivery Systems for Enhancing Solubility, Permeability, and Bioavailability of Sesamin

Sesamin (SSM) is a water-insoluble compound that is easily eliminated by liver metabolism. To improve the solubility and bioavailability of SSM, this study developed and characterized a self-nanoemulsifying drug delivery system (SNEDDS) for the oral delivery of SSM and conducted pharmacokinetic assessments. Oil and surfactant materials suitable for SNEDDS preparation were selected on the basis of their saturation solubility at 37 ± 0.5 °C. The mixing ratios of excipients were determined on the basis of their dispersibility, transmittance (%), droplet sizes, and polydispersity index. An SNEDDS (F10) formulation comprising glyceryl trioctanoate, polyoxyethylene castor oil, and Tween 20 at a ratio of 10:10:80 (w/w/w) was the optimal formulation. This formulation maintained over 90% of its contents in different storage environments for 12 weeks. After the self-emulsification of SNEDDS, the SSM dispersed droplet size was 66.4 ± 31.4 nm, intestinal permeability increased by more than three-fold, relative bioavailability increased by approximately 12.9-fold, and absolute bioavailability increased from 0.3% to 4.4%. Accordingly, the developed SNEDDS formulation can preserve SSM’s solubility, permeability, and bioavailability. Therefore, this SNEDDS formulation has great potential for the oral administration of SSM, which can enhance its pharmacological application value.