Compound R1 Research Articles

Design, synthesis and antidiabetic study of triazole clubbed indole derivatives as α-glucosidase inhibitors

α -Glucosidase is an enzyme present near the brush boundary of the small intestine that is essential in the hydrolysis of carbohydrates to glucose. Because inhibiting this enzyme slows the release of glucose, α-Glucosidase inhibitors are appealing medications for treating diabetes as a carbohydrate-related illness. The present study includes the design, synthesis and antidiabetic potential of novel triazole based indole derivatives as α-glucosidase inhibitor. Among them, the compound R1 was found to be most potent with promising candidate with IC50 value of 10.1 μM and R2 and R3 showed the good inhibitory potency with IC50 values 12.95 μM, 11.35 μM, respectively when compared to the standard drug acarbose having IC50 value of 13.5 μM. In in vivo studies, body weight of the mice was increased when compared to standard drug acarbose, the blood glucose level of the mice was decreased, same as the total cholesterol level, LDL, and triglycerides level decreased in comparison to standard drug. The level HDL was increased as it is a good cholesterol in comparison to standard drug acarbose. Furthermore, these synthesized compounds were docked with α-glucosidase using PDB ID:3WY1 which showed that compound R1 having good docking score −6.734 kcal/mol and compound R2, R3 showed docking score −6.14, −6.10 kcal/mol, respectively when compared with standard acarbose having docking score −4.55 kcal/mol. R1 showed the similar interaction with amino acid PHE166, GLU271, comparison with standard drug Acarbose. The synthesized compounds have been confirmed for antidiabetic activity and may be used for further development of potent compounds.

SYNTHESIS OF PARA-AMINOPHENYL CYCLOPROPYLMETHACRYLATE AND ITS RADICAL COPOLYMERIZATION WITH STYRENE

The synthesis of a new monomer para-aminophenyl cyclopropyl methacrylate (APCM) was carried out, its radical copolymerization with styrene was investigated and some regularities of the process were studied. Its radical copolymerizations with styrene were carried out and the resulting copolymers were established in the structures. Based on the IR-NMR and UV spectra, it was found that the copolymerization process of para-aminophenyl cyclopropyl methacrylate proceeds through the double bond, and the substituents, para-aminophenyl cyclopropyl fragment, remain in the side macrochain. The values of the relative activity constants of monomer were determined and the parameters Q and e were calculated according to Alfrey and Pras. The copolymerization constants of the specified compound (r1) with styrene (r2) calculated by the Feinman-Ross method are r1=0.45, r2=0.22, the values of parameters Q and e: Q=0.024 and e=-2.316, respectively. It was revealed that the resulting copolymer has a sufficiently high biomedical activity, which opens the possibility of using this copolymer as a bactericide

Thiophene-modified donor-[formula omitted]-acceptor compound with an enhanced two-photon absorption response: An ultrafast dynamics study

Comparative investigations were performed to determine how thiophene group modifications affect the two-photon absorption properties of a donor-π-acceptor compound. Specifically, linear absorption and one/two-photon fluorescence spectra, open-aperture Z-scan, time-resolved spectroscopy and quantum chemical calculations were performed. After thiophene modification, the two-photon absorption cross-section of compound R1’ was determined to be 264 GM, exhibiting a 1.6-fold enhancement compared with that of compound R1. A transient absorption spectra experiment together with quantum chemical calculations were performed to investigate the effect of thiophene modification on the ultrafast response and intramolecular charge transfer properties of the dipolar compounds. The results indicate that the thiophene group modification on the conjugated bridge and terminal ends plays an important role in the two-photon absorption and intramolecular charge transfer properties.

COPOLYMERS ON THE BASIS OF (p-CHLOROPHENOXYCARBONYL)-CYCLOPROPYL STYRENE WITH STYRENE AND METHYL METHACRYLATE

The radical copolymerization of (p-chlorophenoxycarbonyl)cyclopropyl styrene with styrene and methyl methacrylate has been carried out. New cyclopropane-containing copolymers have been obtained. It has been established that the synthesized copolymers due to peculiarities of their structure and polyfucntionality, namely with content of carbonyl and cyclopropane groups sensitive to UV irradiation in the macromolecule have photosensitivity. The constant values of relative activity of monomers have been determined and Q-e parameters on Alfrey and Price have been calculated. The copolymerization constants of this compound (r1) with styrene and methyl methacylate (r2), calculated on Fineman-Ross method are: r1 = 1.1 and1.05, but r2 = 0.56 and 0.48, respectively; Q and e parameters values: Q1 = 3.1 and 2.4, e1 = –1.4 and –0.8, respectively. The photochemical structuring has been investigated and it has been shown that the structuring process proceeds due to of cyclopropane ring opening and carbonyl group. The composition and structure of these copolymers have been established and their some characteristics (heat resistance, hardness, adhesive strength, water absorption) have been investigated. The structuring process has been also studied and it has been established that the synthesized copolymer has relatively high photosensitivity (50–55 cm2J-1)

Paraoxonase Mimic by a Nanoreactor Aggregate Containing Benzimidazolium Calix and l-Histidine: Demonstration of the Acetylcholine Esterase Activity.

An anion-mediated preorganization approach was used to design and synthesize the benzimidazolium-based calix compound R1⋅2 ClO4 - . X-ray crystallography analysis revealed that the hydrogen-bonding interactions between the benzimidazolium cations and N,N-dimethylformamide (DMF) helped R1⋅2 ClO4 - encapsulate DMF molecule(s). A nanoreactor, with R1⋅2 ClO4 - and l-histidine (l-His) as the components, was fabricated by using a neutralization method. The nanoreactor could detoxify paraoxon in 30 min. l-His played a vital role in this process. Paraoxonase is a well-known enzyme used for pesticide degradation. The Ellman's reagent was used to determine the percentage inhibition of the acetylcholinesterase (AChE) activity in the presence of the nanoreactor. The results indicated that the nanoreactor inhibited AChE inhibition.

SYNTHESIS OF 1-(P-VINYLPHENYL)-2- DIETHYLAMINOMETHYLCYCLOPROPANE AND ITS RADICAL COPOLYMERIZATION WITH METHYL METHACRYLATE

The radical copolymerization of 1-(p-vinylphenyl)-2-diethylaminomethylcyclopropane with methyl methacrylate was carried out and some regularities of the process examined. Values of constants of relative activity of monomers were determined and Q-e parameters calculated on Alfrey and Price. Copolymerization constants of this compound (r1) with methyl methacrylate (r2), calculated on the FinemanRoss method, are as follows: r1 = 0.95, r2 = 0.33, Q and e parameter values: Q1 = 1.80, e1 = -0.72, respectively. The photochemical structuring of the copolymer was studied. It was established that the obtained copolymer has a sufficiently high biomedical activity which opens up the possibility of its using as bactericides and fungicides

Solvent directed discrimination of metal ions using a coumarin-pyridine fluorescence receptor

The development of reliable methods for large scale discrimination of versatile metal ions is meaningful to avoid metal poisoning accidents and investigate their biological roles. Herein, a solvent directed strategy is reported for readily construction of a robust and powerful fluorescent sensor array R1SA for effective metal ion discrimination. The four sensors of R1SA were obtained by simply dissolving a unique coumarin-pyridine compound R1 in four different solvents, i.e., methanol, ethanol, acetonitrile and DMSO respectively. The sensing mechanism was based on the fact that R1 showed fluorescence responses towards various metal ions in a solvent directed manner. R1SA was able to generate distinct fluorescence response patterns for 12 kinds of metal ions including Cd2+, Co2+, V3+, Sn2+, Fe3+, Cr3+, Hg2+, Mn2+, Cu2+, Bi3+, Pb2+, and Ag+. It was able to discriminate these 12 metal ion species reliably in both aqueous solution and serum media, and identify the unknown metal ion in serum samples with high accuracy. Moreover, R1SA was also successfully applied to discriminate metal ion mixtures of Sn2+/Pb2+, Cd2+/Hg2+ and the valence states of iron in water and 5 % serum media, indicating that it can be considered as a practical tool for investigating the biological roles of iron.

Structural phase diagram and magnetic properties of Sc-substituted rare earth ferrites R1−xScxFeO3 (R = Lu, Yb, Er, and Ho)

We have studied the structural stability of Sc-substituted rare earth (R) ferrites R1−xScxFeO3 and constructed a structural phase diagram for different R and x. While RFeO3 and ScFeO3 adopt the orthorhombic and bixbyite structure, respectively, the substituted compound R1−xScxFeO3 may be stable in a different structure. Specifically, for R0.5Sc0.5FeO3, the hexagonal structure can be stable for small R, such as Lu and Yb, while the garnet structure is stable for larger R, such as Er and Ho. The formation of the garnet structure of R0.5Sc0.5FeO3 compounds, which requires that Sc occupies both the rare earth and the Fe sites, is corroborated by their magnetic properties.

Bioactive compounds from mangrove derived rare actinobacterium Saccharomonospora oceani VJDS-3.

A rare actinobacterium was isolated from Nizampatnam mangrove ecosystem of Andhra Pradesh, India, and was screened for its ability to produce bioactive compounds. The potential strain was identified as Saccharomonospora oceani VJDS-3 by polyphasic taxonomy. Purification of the biologically active compounds by column chromatography led to the isolation of three compounds, namely methoxy ethyl cinnamate (ethyl(E)-3-(4-methoxyphenyl)acrylate) (R1), 4-hydroxy methyl cinnamate (methyl(E)-3-(4-hydroxyphenyl)acrylate) (R2) and 4-methylbenzoic acid (R3). The structure of the compounds was elucidated on the basis of spectroscopic analysis including FTIR, EIMS, 1HNMR and 13CNMR spectroscopies. The antimicrobial activity of the bioactive compounds produced by the strain was tested against a panel of bacteria and fungi, and expressed in terms of minimum inhibitory concentration. Compound (R1) exhibited higher antimicrobial potential (50µg/ml) against Staphylococcus aureus, Bacillus megaterium and Candida albicans compared to R2 and R3. Antioxidant activity of compounds was determined by DPPH and ABTS radical scavenging activities. The results revealed that compound R3 effectively scavenged DPPH (73.08±1.29) and ABTS (99.74±0.00) radicals at a concentration of 25 and 50µg/ml, respectively. Antidiabetic and anti-obesity activities were evaluated by inhibitory potential of compounds against alpha-glucosidase, alpha-amylase and pancreatic lipase by spectrophotometric assays. Compound R1 showed effective inhibition against alpha-glucosidase (66.8±1.2) at 20µg/ml while moderate to weak activities were found against alpha-amylase and pancreatic lipase. To the best of our knowledge, this is the first report on the isolation of supra said compounds from the genus Saccharomonospora.

Acupuncture combined with ganglioside and mecobalamine injections can relieve the symptoms of idiopathic facial palsy

Objective To observe the clinical effect of acupuncture combined with ganglioside and mecobalamine injections on idiopathic facial palsy (IFP). Methods A total of 120 IFP patients were divided into a ganglioside group, a mecobalamine group and a consociation group, each of 40. All were given routine drug and acupuncture treatment, while the ganglioside and mecoblamine groups were additionally provided with the corresponding injections of ganglioside and mecobalamine, respectively. The treatment was administered once daily for a total of 14 days. All the groups were evaluated using the House-Brackmann facial nerve grading system before and after the interventions of 14 days ended. The compound muscle action potential (CMAP) wave amplitude and R1 incubation, the motor nerve conduction velocity (MCV) and the sensory nerve conduction velocity (SCV) of the affected facial nerves were observed and compared before and after the 14 days of treatment. Results The total effectiveness rate of the consociation group (95.0%) was significantly higher than that of the ganglioside (90.0%) or the mecobalamine group (87.5%). After the treatment the CMAP wave amplitude had improved significantly and the R1 latency had shortened significantly in the consociation group compared to the other 2 groups. The average MCV and SCV of the consociation group had also improved significantly compared with the other two groups. Conclusion Acupuncture combined with ganglioside and mecobalamine injections is an effective therapy for idiopathic facial palsy. It can improve the patient′s clinical symptoms, shorten the CMAP wave amplitude and R1 latency on the affected side and improve MCV and SCV. Key words: Acupuncture; Gangliosides; Mecobalamine; Idiopathic facial palsy; Muscle activation potentials; R1 latency; Nerve conduction velocity

Investigation of Photosensitivity of Copolymer with (P-Vinyl Phenyl) Cyclopropyl Methyl Cinnamate

The radical copolymerization of (p-vinyl phenyl) cyclopropyl methyl cinnamate with methyl methacrylate has been studied. New cyclopropane-containing photosensitive copolymers have been prepared. The constant values of relative activity of monomers have been determined and the parameters of Q-e on Alfrey and Price have been calculated. The copolymerization constants of this compound (r1) with methyl methacrylate (r2) calculated on Fineman-Ross method are r1 =1.05, r2 = 0.4, respectively; parameter values Q and e: Q1 =2.5, e1 = -0.9, respectively. The composition and structure of these copolymers have been established. The photochemical investigations of the synthesized copolymer have been carried out. It has been established that a structuring proceeds due to opening of cyclopropane ring and carbonyl groups and also double bond in cinnamate fragment.

Antimicrobial and Antimalarial Activity of Novel Synthetic Mononuclear Ruthenium(II) Compounds

AbstractThe present work was aimed that the two Ruthenium compounds namely, [Ru(A)2(B)]Cl2, where A = 1,10‐phenanthroline; B = 2‐NO2‐phenyl thiosemicarbazone (Compound R1)/2‐OH‐phenyl thiosemicarbazone (Compound R2) have been tested for antibacterial activity at the concentrations of 1 mg/mL against various Gram‐Positive organisms (Lactobacillus, Staphylococcus pyrogenes, Bacillus subtilis, Staphylococcus aureus & Bacillus megatarium) and Gram‐Negative organisms (Pseudomonas aeruginosa, Escherichia coli, Proteus vulgaris, Enterobacter aerogenes, Salmonella paratyphi, Klebsiella pneumonia & Proteus mirabilis). The compounds were also tested for antifungal activity against Aspergillus clavatus, Aspergillus niger, Colletotrichum & Penicillium notatum by using agar diffusion assay and antimalarial activity against Plasmodium falciparum (Strain 3D7) using MTT assay. The results concluded that the compound R1 exhibited significant antibacterial activity than R2 against Gram‐Negative bacteria with zones of inhibition ranging from 15‐20 mm. and mild antibacterial activity against Gram‐Positive bacteria in comparison to tetracycline, streptomycin and rifampicin. These complexes were found to have moderate antifungal activity with no activity was however observed against Aspergillus niger. The compound, R1 exhibited antimalarial activity at 10 μg/mL, whereas R2 did not show antimalarial activity upto 50 μg/mL. Sensitivity to the compounds was greatest in the gram‐negative bacteria, followed by the gram‐positive bacteria and fungi.

Synthesis, crystal structures and studies on Hg2+ sensing by the diazo derivatives of sulfathiazole and sulfamethoxazole

Diazocoupling of sulfathiazole and sulfamethoxazole with 2,4-pentanedione led to the syntheses of compounds R1 and R2. These were fully characterized by single crystal X-ray diffraction studies in conjunction with UV–visible, IR, 1H NMR, and mass spectral studies. Both the compounds were further screened for their possible use in metal ion recognition. Interestingly, compound R1 showed a selective naked-eye response for Hg2+, while R2 did not give a color change for any metal ions. These results can be understood in terms of a solvent-assisted low-energy absorption band in R1 that disappeared upon interaction with Hg2+. This absorption band was not observed in the case of compound R2 that consequently failed to show any naked-eye color change in the presence of metal ions.

Novel Mononuclear Ruthenium(II) Compounds in Cancer Therapy

The present study was conducted to evaluate in vivo anticancer activity of two novel mononuclear ruthenium(II) compounds, namely Ru(1,10-phenanthroline)2(2-nitro phenyl thiosemicarbazone)Cl2 (Compound R1) and Ru (1,10-phenanthroline)2(2-hydroxy phenyl thiosemicarbazone)Cl2 (Compound R2) against Ehrlich ascites carcinoma (EAC) mice and in vitro cytotoxic activity against IEC-6 (small intestine) cell lines and Artemia salina nauplii using MTT [(3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide)] and BLT [brine shrimp lethality] assays respectively. The test ruthenium compounds at the doses 2 and 4 mg/kg body weight showed promising biological activity, especially in decreasing tumor volume, viable ascites cell counts and body weights. These compounds prolonged the life span (% ILS), mean survival time (MST) of mice bearing-EAC tumor. The results for in vitro cytotoxicity against IEC-6 cells showed the ruthenium compound R2 to have significant cytotoxic activity with a IC50 value of 20.0 μg/mL than R1 (IC50=78.8 μg/mL) in the MTT assay and the LC50 values of R1 and R2 compounds were found to be 38.3 and 43.8 μg/mL respectively in the BLT assay. The biochemical and histopathological results revealed that there was no significant hepatotoxicity and nephrotoxicity associated with the ruthenium administration to mice.

Stabilization of TGB Phase in the Binary Mixture of Rod-Shaped Compounds

A miscibility study of two cholesterol based rod-shaped compounds (R1 and R2) is presented. Both the compounds possess in common enantiotropic liquid crystalline phase sequence Cr → SmA → N* → Isotropic, which is generally exhibited by cholesterol-based compounds. Additionally, one of the rod-shaped compounds (R1) possesses a twist-grain boundary (TGB) phase over a short temperature range. In the binary mixture of these two rod-shaped compounds the TGB phase was stabilized over a long temperature range compared to that in the individual molecule R1. In the binary mixture up to 20% (w/w) of compound R1 possessing the TGB phase exhibited enhancement of the temperature range of the TGB phase compared to that of individual compound R1. Further gradual increase of percentage of R1 in the binary mixture did not show any enhancement of the TGB phase compared to that of individual R1.

Synthesis of a new gadolinium complex with a high affinity for human serum albumin and its manifold physicochemical characterization by proton relaxation rate analysis, NMR diffusometry and electrospray mass spectrometry

A novel gadolinium complex, derived from Gd–DTPA (DTPA: diethylenetriaminepentaacetic acid) and sulfaphenazole, intended to be a potential MRI contrast agent and to interact with human serum albumin (HSA), was synthesized and characterized. Its relaxometric properties were evaluated in water, and its binding to HSA was investigated by three techniques: proton relaxation rate analysis, NMR diffusometry, and electrospray mass spectrometry. The complex has a higher relaxivity than the parent compound (r1=7.8s−1mM−1 at 310K and 0.47T and 7.7s−1mM−1 at 310K and 1.41T), a fast water exchange, and a very good stability versus zinc(II) transmetallation. All techniques agree with a high affinity of the complex for HSA, and competition experiments indicate that this contrast agent competes with ibuprofen for HSA.

Effects of Organoantimony(III) Compounds of Sterically Hindered Bifunctional Tetradentate Ligands on the Reproductive System of Male Rats

The antifertility activity of organoantimony(III) complexes PhSb[RC(NC6H4S)CH2(NC6H4S)CR′] {R' = CH3 (R1) and R = R' = CF3 (R2)} derived from corresponding sterically hinlered bifuinctional tetradentate ligands in the male rats was determined. The administration of compounds R1 and R2 at the dose level of 20 mg/kg. b. wt. siignificantly reduced the weights of testes and epididymides. Auxiliary glands showed a significant reduction after the treatment of compound R1 only. Treated animals showed a notable depression of spermatogenesis. The preleptotene spermatocytes were decreased by 76.19 and 47.06; the secondary spermatocytes by 87.4% and 54.87337; and the step-19 spermatids by 72.9 and 46.77% respectively, following the compound R1 and R2 treatment. Reduced sperm count and motility resulted in 100% negative fertility in both the treated groups. A significant fall in the content of various biochemical parameters of eproductive tissues was observed after R1 and R2 treatment in comparison to controls.

Coexistence of Superconductivity and Ferromagnetism in Electron and Nuclear Magnets

A phenomenological model uniting the London model of superconductivity and the micromagnetic approach to ferromagnetism is applied to new examples of coexistence of ferromagnetism and superconductivity revealed in recent experiments: (i) Type-I superconductivity in a nuclear ferromagnet AuIn 2 ; (ii) Type-II high-Tc superconductivity in a compound R 1.5 Ce 0.5 RuSr 2 Cu 2 O 10 which is weakly ferromagnetic.

Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm.

Botulinum toxin treatment improves dystonic blepharospasm by inducing transient paresis of the orbicularis oculi muscle. It is not known if it also reduces the enhanced brainstem neuronal excitability found in this disorder. We have performed conventional electromyography (EMG) and blink reflex excitability studies on fifteen patients with blepharospasm before and after botulinum toxin treatment. Denervation signs were found with needle EMG in all treated muscles. Amplitude of the facial compound muscle action potential (CMAP) and R1 response was reduced after botulinum toxin injections. In blink reflex excitability studies, the recovery of R2 response was enhanced after treatment even when patients were tested at the time of maximal benefit from botulinum toxin injections. The results suggest that there is little influence of botulinum toxin treatment upon the enhanced excitability of brainstem interneurons in patients with blepharospasm.