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.

Targeting the chemokine receptor CXCR4 with histamine analogue to reduce inflammation in juvenile arthritis: a proof of concept for COVID-19 therapeutic approach

Among immune cells, activated monocytes play a detrimental role in chronic and viral-induced inflammatory pathologies. The uncontrolled activation of monocytes and the subsequent excessive production of inflammatory factors damage bone-cartilage joints in Juvenile Idiopathic Arthritis (JIA), a childhood rheumatoid arthritis (RA) disease. Inflammatory monocytes also exert a critical role in the cytokine storm induced by SARS-CoV2 infection in severe COVID-19 patients. The moderate beneficial effect of current therapies and clinical trials highlights the need of alternative strategies targeting monocytes to treat RA and COVID-19 pathologies. Here, we show that targeting CXCR4 with small amino compound such as the histamine analogue clobenpropit (CB) inhibits spontaneous and induced-production of a set of key inflammatory cytokines by monocytes isolated from blood and synovial fluids of JIA patients. Moreover, daily intraperitoneal CB treatment of arthritic mice results in significant decrease in circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption leading to reduction of disease progression. Finally, we provide the prime evidence that the exposure of whole blood from hospitalized COVID-19 patients to CB significantly reduces levels of key cytokine-storm-associated factors including TNF-α, IL-6 and IL-1β. These overall data show that targeting CXCR4 with CB-like molecules may represent a promising therapeutic option for chronic and viral-induced inflammatory diseases.

Direct Surface Modification of Polycaprolactone-Based Shape Memory Materials to Introduce Positive Charge Aiming to Enhance Cell Affinity

In this study, the introduction of a positive charge on the surface of a shape memory material was investigated to enhance cell affinity. To achieve this, the direct chemical modification of a material surface was proposed. Sheet-type, crosslinked poly(caprolactone-co-α-bromo-ɤ-butyrolactone) (poly(CL-co-BrBL)) were prepared, and the direct reaction of amino compounds with bromo groups was conducted on the material surface with a positive charge. Branched poly(CL-co-BrBL) was prepared, followed by the introduction of methacryloyl groups to each chain end. Using the branched macromonomers, stable and sheet-type materials were derived through UV-light irradiation. Then, the materials were soaked in an amino compound solution to react with the bromo groups under various conditions. Differential scanning calorimetry and surface analysis of the modified materials indicated that 10 vol% of N, N-dimethylethylenediamine in n-hexane and 1 h soaking time were optimal to maintain the inherent thermal properties. The achievement of increased luminance and a positive zeta potential proved that the direct modification method effectively introduced the positive charge only on the surface, thereby enhancing cell affinity.

Identification of dipyrrolone pigments and their precursors formed in the Maillard reaction of carnosine and pentose under weakly acidic conditions

Colored compounds formed by the Maillard reaction of carnosine with xylose or glucose were investigated in this study. Yellow pigments showing an absorption maximum at 450 nm were found in a heated solution of carnosine with xylose at pH 5.0. These pigments were then isolated and identified as dicarnosyl-dipyrrolones A and B. The generation of dipyrrolones in the absence of lysine suggests that dipyrrolone pigments can be formed by pentose as well as every amino compound such as amino acids, peptides and proteins possessing a free amino group. Analysis of α-dicarbonyls using LC-MS/MS showed that pentosone, 1-deoxypentosone, 3-deoxypentosone (3-DP), and methylglyoxal were predominantly generated via degradation of Amadori compounds. Also, a potential formation pathway of dypyrrolones was established, indicating that an Amadori compound which could form 3-DP is likely to play a role as a main precursor for dipyrrolones.

Micro Evaluation of Sulphonamide in Biological Samples by Coupling Reaction

Sulphonamide is considered a turning point for therapeutic science. Structural changes in sulphonamide can lead to the formation of various drugs used for combating different diseases. Sulphonamide can be used in different applications, such as, antitumor agents, carbonic anhydrase inhibitors, anti-bacterials, hypoglycaemic agents, protease inhibitors, and diuretics. The most important thing for this assay is to find a modified approach to assess sulphonamide by utilizing an organic reaction that depends on a process of coupling between our target material (sulphonamide) with 4-amino antipyrine in basic media of phosphate buffer (pH = 11.3), forming a colored complex containing a higher molar absorptivity (wavelength = 457 nanometers). A preliminary investigation test was done to determine the typical condition for this reaction to determine the concentration curve for the interval 8.25 × 10-9 to 1.15 × 10-2 ppm, and the absorptivity molar was 2.1 × 104 L.mol-1.cm-1, RSD value greater than 1.12%, with a percentage of recovery of approximately 99.88%. We obtained the result and got the approved mole ratio for this reaction about 1:1 (sulphonamide:diazotized amino compound); the value of the stability factor reached 2.8 × 106 L.mol-1. This proposal could be used for a fair assessment for sulphonamide determination, which has different advantages, such as, low-cost economy, no need for an expert, simplicity, no need for more time, and high-quality results in the requirement of rapid and excellent determination. This approach can be utilized for validation of sulphonamide in different active biological samples with higher efficiency.

A review on versatile applications of novel Schiff bases and their metal complexes

Metal complexes synthesized from Schiff bases and furthermore Schiff bases are versatile in nature. Such types of compounds were prepared from the condensation of an amino compound with carbonyl compounds (aldehyde or ketone) during which the carbonyl group is replaced by an imine or azomethine group. Schiff bases and their derivatives are widely employed in industries, polymers, dyes and medicative and pharmaceutical fields and additionally exhibit biological activities like antibacterial, antifungal, anti-inflammatory, antimalarial, antiviral, and antipyretic properties. Many Schiff base metal complexes exhibit glorious catalytic activities in numerous mechanisms. Their several applications in homogenous and heterogeneous catalysis were according troughout last decade. Several Schiff base complexes were helpful for their application as catalysts in reactions involving at high temperatures because of the high thermal and moisture stabilities. This text totally based on literature review with examples of the most promising applied Schiff bases and their complexes in several areas, summarizing the applications of Schiff bases and their numerous derivatives and complexes.

Synthesis, identification and thermal study of some new inorganic polymers based on bis-dithiocarbamate ligands with silicone, tellurium and some transition metals

Introduction: In recent years, there has been considerable interest in dithiocarbamate complexes because of its diverse biological roles, very few reports have been made on polymeric bis- dithiocarbamate compounds with carbon chain of n-propyl or hexamethelene with transition metals in addition of the absence of any report of organosilicone or tellurium halides with such compounds Our interest in this report based on the preparation of new series of polymers with an expected activity as a fungi side compounds followed by the using of prepared amino compound as a hardners for epoxy paints Materials and Methods: A new polymers of the general structures –(MS2CNH(CH2)6NHCS2M-)n where [M= Cu, Cd, Mn and Zn] and –(M(R)2S2CNH(CH2)nNHCS2MR2-)m where [M= Si,R=CH 3 , n= 2 ,3 and 6 ; M=Te , R= Br , n= 2 ,3 and 6 ; M=Co, Ni R=Cl ; n= 6] have been prepared by reaction of MX2 where M= Ni ,Co, Cd , Mnor Zn , X= Cl ; M=Cu , X= SO4 , and dimethyl dichloro silane, tellurium tetrabromide with the corresponding sodium salts of bis-dithiocarbamateligands. Results and Discussion: Dimethyldichloro silane is a very sensitive material to O-H group, in addition to that, TeBr4 decomposed rapidlyin water so, a series solvents may be useful with such sensitive chemicals to water , in the other hand, dithiocarbamate ligands which is usually prepared in aqueous and alcoholic solution , must be prepared and isolated carefully to apply the other steps of synthesis using a chloroform solution as a solvent. It seems for the first view for dithiocarbamato ligands it may act as a bi dentate ligands using two sulphur donating atoms that is clearly appeared in common complexes such as diethyl dithiocarbamato or pipyridyl, morpholino dithiocarbamato with representation metal elements, even in such type of elements a sulfur bridges may formed. In this study, it showed clearly that Zinc and Cadimium polymers are diamagnetic polymers that is mean that these polymers are with oxidation state equal to (II) and a tetrahedral configuration Conclusions: The study showed that the new silicone polymers act as a stable polymers compared with others. All new polymers are of a high stability with large values of char contain with commercial epoxy. Among silicone polymers, the polymerwith carbon chain equal to 3 is more stable than that with 2 carbon atoms while the silicone polymer with 6 carbon atoms is the less stable one, may thermal treatment caused decomposition combined.

Synthesis, Crystal Structure and IR Spectrum studies of 2-(4-Methyl-2-phenyl-4,5-dihydro-oxazol-4-ylmethyl)- isoindole-1,3-dione

The organo-amino compound of title 2-(4-methyl-2-phenyl-4,5-dihydro-oxazol-4-ylmethyl)-isoindole-1,3-dione was synthesized by the mixture of (4-methyl-2-phenyl-4,5-dihydrooxazol-4-yl)methyl-4-methylbenzenesulfonate and isoindoline-1,3-dione in N,N-dimethylformamide with a yield of around 65%. The structural study of the compound, C19H16N2O3, is realized using single crystal X-Ray diffraction which shows that this compound crystallizes in the monoclinic system (P21/c, Z = 4) with the unit cell parameters: a = 14.3728 (13) Å, b = 9.6829 (10) Å, c = 11.8964 (12) Å and β = 107.384 (3). The refinement of the structure by the least-squares method with complete matrix leads to the following reliability factors R/Rw are 0.044/0.130.In the crystal, the molecules are linked together by hydrogen bonds and π…π interactions.The Infrared spectroscopic studies show the bands confirming the presence of the groups C=O, C-O, C-N, -CH3, -CH2 and =CH.

Position-Selective Synthesis and Biological Evaluation of Four Isomeric A-Ring Amino Derivatives of the Alkaloid Luotonin A

Following two orthogonal synthetic routes, a series of all four possible A-ring amino derivatives of the natural product Luotonin A (a known Topoisomerase I inhibitor) was synthesized. In both strategies, intramolecular cycloaddition reactions are the key step. The target compounds were obtained in good yields by mild catalytic transfer hydrogenation of the corresponding nitro precursors. In-vitro evaluation of the antiproliferative activity towards human tumor cell lines revealed the 4-amino compound (5b) to be the most effective agent, showing an interesting profile of cytotoxic activity. Among other effects, a significant G2/M cell cycle arrest was observed for this compound, suggesting that either Topoisomerase I is not the only biological target, or that some atypical mechanism is responsible for inhibition of this enzyme.

Rekayasa Chitosan Sebagai Pengawet Dan Meningkatkan Kadar Protein Dalam Tahu [Technologi Engineering Chitosan As A Preservative And Elevated Levels Of A Protein On Tofu ]

Chitosan is the potential to serve as a food preservative, because chitosan has polikation positively charged so that it can inhibit the growth of microbes and are able to bind to the compounds negatively charged such as protein, polysaccharides, nucleid acid, heavy methal and others. In addition, molecules of chitosan has an N capable of forming amino compound which is a component of protein and amine moieties on the H atoms which facilitates chitosan interact with water through hydrogen bonds. Know who manufactured this process at the time of processing is still done traditionality. So that power save know produced has a fairy low level of durability. This study used a randomized complete design methods, experimental design was used with tree treatment with five replicate. Treatment imposed in the research include ; treatment with the awarding of chitosan as much as 1%, granting of chitosan treatment B as much as 2%, granting of chitosan treatment C by as much as 3%. Form the results of our study, obtained a good treatment doses for food out of 3%. The doses may be extend save out to 5 days in the future at room temperature and increase the levels of protein know 0,5 – 1,5 %.