Synthesis of Fluorinated Heterocyclic Compounds for Pharmacological Screening

A series of derivatives of (E)-6-chloro-5-fluoro-2-styryl-1H-benzo[d]imidazole, and 5-fluoro-2-methylN-phenyl-1H-benzo[d]imidazol-6-amine was synthesized. Compounds confirmed by melting point, FT-IR, 1HNMR, Mass spectral analytical techniques and predicted for their ADME, Pharmacokinetic properties.Synthesized compounds screened for better antibacterial and antiinflammatory activity. To synthesize a series of novel trisubstituted fluorinated benzimidazole derivatives and evaluate the physicochemical, ADME and pharmacokinetic properties and biological activity. The starting material Flouro-chloro-aniline ona series of reaction such as acetylation, nitration, deacetylation followed by reductionto get 4-fluoro-5-chloroorthophenylene diamine. The di-amino compound cyclized with acetyl chloride to obtain 6-chloro-5-fluoro-2- methyl-1H-benzimidazole which on reaction with various aromatic aldehyde forms series of compounds 31(a-h), and with various anilines forms compounds 32(a-j). Physicochemical, ADME and pharmacokinetic properties predicted Insilco. Antimicrobial activity screened by Agar diffusion method. In vitro antiinflammatory activity screened by protein denaturation assay.The compounds synthesized confirmed by melting Point, FT-IR, 1HNMR, Mass spectral analytical techniques and predicted for their ADME, Pharmacokinetic properties in silico. The compounds screened and confirmed with moderate antimicrobial, and in vitro antiinflammatory activity.

Phytochemical and Antiinflammatory Properties of Etlingera elatior (Jack) RM Sm.: A Review

Background: Inflammation is part of the biological response that exists in vascular tissue to harmful stimulation. Using medicinal plants can help to treat inflammation. Etlingera elatior (Jack) RM Sm. is one of the medicinal plants. Objective: The review aims to present information from some research about the phytochemical and antiinflammatory activity of Etlingera elatior (Jack) RM Sm. Methods: The review provides evidence in the literature for the phytochemical and antiinflammatory activity of Etlingera elatior (Jack) RM Sm. from 2010-2021. The bibliographic databases were used as the primary sources of information (Google Scholar, ScienceDirect, and PubMed). The keywords in this search were "Phytochemical or Phytochemistry" and "Etlingera elatior (Jack) RM Sm. or Nicolaia speciosa Horan" and "Anti-inflammatory or Anti Inflammatory." Five studies were included in this review according to the required criteria. Results: Phytochemical compounds contained in Etlingera elatior (Jack) RM Sm. dominated by flavonoids, saponins, tannins, terpenoids phenolic, and volatile oils which are widely distributed in leaves, flowers, stems, and rhizomes. Pharmacological studies reported that Etlingera elatior (Jack) RM Sm. shown anti-inflammatory activity by inhibiting regulation of NF-κB-p65 expression. It can reduce carrageenan-induced edema in the soles of rat's feet and stabilize erythrocyte membranes. Conclusion: Etlingera elatior (Jack) RM Sm. is the potential medicinal plant to develop as anti-inflammatory therapy.

HPTLC analysis and anti-inflammatory activity of Plectranthus amboinicus (Lour.) leaves

Plectranthus amboinicus (Lour.) Spreng. are generally used in Chinese folk medicine for treating fever, cough, mumps, sore throats, and mosquito bite. The current study was therefore carried out to provide vital pharmacological details about the leaf. This study investigated the anti-inflammatory properties of ethanolic extract from Plectranthus amboinicus. The leaves of Plectranthus amboinicus were rinsed, air dried and then powdered using machine. The ethanol extract of the plant was used for phytochemical analysis to identify the constituents present in the plants. HPTLC analysis was carried out to investigate its secondary metabolite profile by using the solvent mixture. The anti-inflammatory effect was analysed by inhibition of protein denaturation assay. The hypotonicity induced haemolysis was observed from 100µg/ml to 500µg/ml of extract concentration. The results proved that the ethanolic leaf extract of P.amboinicus has antiinflammatory activity. The presence of flavonoid, quercetin in plant extract was confirmed by HPTLC analysis and these flavonoids may be responsible for the antiinflammatory activity. Further studies are needed to the development of potential drug that may be used for various pharmacological activities.

Evaluation of effect of Calotropis gigantea root bark in some animal models of Wister albino rats

Background: Calotropis gigantea is a well-documented traditional medicinal plant useful for many disease conditions. The present study deals with the effect of alcoholic extract of roots bark of Calotropis gigantean in some animal models.Methods: Acute anti-inflammatory activity of root extract was assessed on carrageenin induced paw edema and chronic antiinflammatory activity on cotton pellet granuloma formation in rats and compared with standard diclofenac sodium. Antiasthmatic activity was assessed in histamine and actylcholine induced bronchoconstriction in guinea pigs.Results: 100 and 200 mg/kg p.o. root extract of CG showed significant anti-inflammatory and bronchodilator activity. Antiinflammatory activity was higher than Diclofenac Sodium 50mg/kg. The combination of low dose diclofenac sodium 25mg/kg potentiated the effect. Inhibitory effect on synthesis and release of various inflammatory mediators might contribute to both of these actions. Steroid like phytoconstituents might be responsible for these effects. Further research is needed to understand the exact mechanism behind these effects.Conclusions: In the present study Calotropis gigantea root bark exhibited anti-inflammatory activity in animal models.

Functional monovalency amplifies the pathogenicity of anti-MuSK IgG4 in myasthenia gravis

Human immunoglobulin (Ig) G4 usually displays antiinflammatory activity, and observations of IgG4 autoantibodies causing severe autoimmune disorders are therefore poorly understood. In blood, IgG4 naturally engages in a stochastic process termed “Fab-arm exchange” in which unrelated IgG4s exchange half-molecules continuously. The resulting IgG4 antibodies are composed of two different binding sites, thereby acquiring monovalent binding and inability to cross-link for each antigen recognized. Here, we demonstrate that this process amplifies autoantibody pathogenicity in a classic IgG4-mediated autoimmune disease: muscle-specific kinase (MuSK) myasthenia gravis. In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness, whereas the same antibodies in their parental bivalent form were less potent or did not induce a phenotype. Mechanistically this could be explained by opposing effects on MuSK signaling. Isotype switching to IgG4 in an autoimmune response thereby may be a critical step in the development of disease. Our study establishes functional monovalency as a pathogenic mechanism in IgG4-mediated autoimmune disease and potentially other disorders.

PHYTOCHEMICAL COMPOSITION AND ANTIINFLAMMATORY ACTIVITY OF NELUMBO NUCIFERA GAERTN

Objective: Inflammation is a process of injuries caused by physical, chemical, and biological factors. Nitric oxide (NO) plays an important role in theregulation of various pathological and pathophysiological processes. Overproduction of NO induces tissue damage associated with acute and chronicinflammations. This study was conducted to determine the phytochemical composition and the NO inhibitory properties of Nelumbo nucifera extractsin lipopolysaccharide(LPS)-stimulated macrophage cell line.Methods: The dried leaf, stalk, and flower materials of roseum plenum and album plenum (AP) were extracted with 95% ethanol solvents. Thephytochemical compounds of the extraction were analysed by gas chromatography-mass spectrometry. The cytotoxic assay of extracts againstmacrophage cells was conducted using resazurin. The NO was determined using LPS-induced RAW264.7 cells to measure inhibitory activity of extracton the production of NO.Results: The extracts from Lotus, which exhibited the non-cytotoxic to the RAW264.7 cells. The AP-stalk extracts were capable to reduce the NO levelin LPS-activated RAW264.7 cells. GC-MS analysis of AP-stalk extraction revealed pharmacologically active compounds.Conclusion: The results conduct that the AP-stalk extract effectively inhibited the NO production and may be useful in preventing inflammatorydiseases mediated by excessive production of NO. Bio-active phytoconstituents from AP stalk extract could potentially be used for anti-inflammation.These data also suggest that AP-stalk extract may serve as a good indicator of the pharmacological activities of medicinal plants.