Synthesis, Physicochemical, Computational and Biological Evaluation of Phenylurea Derivatives as CNS agents

Background: A series of phenylurea derivatives were designed and synthesized, The target compounds were subjected to pharmacological studies. Various other parameters such as physicochemical properties, computational studies, and % similarity were also calculated. Materials and Methods: The synthesis of the target compounds has been carried out by reaction of Phenylurea with chloroacetyl chloride to afford 1-(2-chloroacetyl)-3-phenylurea, which further reacted with substituted anilines. All the reactions were monitored by TLC. All the target compounds were purified by recrystallization and characterized by spectroscopic methods. Physicochemical parameters and Log P values of the synthesized derivatives were also calculated. It identified compounds that have the prospect to cross the blood-brain barrier (BBB) and are CNS active. Skeletal muscle relaxant activity was also carried out using the Rotarod method. Results: The data of Log P indicated that the synthesized compounds have the potential to cross the BBB, so they are CNS active. Pharmacological activities of the derivatives showed that the compounds containing chloro group have moderate skeletal muscle relaxant activity. The test compounds possess significant differences between the control group and the treated group. Conclusion: The synthesized derivatives containing chloro group were found to be more potent when compared to standard drug Diazepam. Various others parameters studied revealed that the drug has the potency to cross the blood-brain barrier.

Crystal structures of three N-acylhydrazone isomers

The crystal structures of three isomers of (E)-4-chloro-N-{2-[2-(chlorobenzylidene)hydrazinyl]-2-oxoethyl}benzenesulfonamide, namely, (E)-4-chloro-N-{2-[2-(2-chlorobenzylidene)hydrazinyl]-2-oxoethyl}benzenesulfonamide (I), (E)-4-chloro-N-{2-[2-(3-chlorobenzylidene)hydrazinyl]-2-oxoethyl}benzenesulfonamide (II) and (E)-4-chloro-N-{2-[2-(4-chlorobenzylidene)hydrazinyl]-2-oxoethyl}benzenesulfonamide (III), with the general formula C15H13Cl2N3O3S are described, with the chloro group in ortho, meta and para positions in the benzylidene benzene ring. All the three isomeric compounds crystallize in the centrosymmetric triclinic P\overline{1} space group with one molecule each in the asymmetric unit and two molecules in the unit cell. The dihedral angles between the two phenyl rings are 11.09 (14), 53.79 (18) and 72.37 (11)° in (I), (II) and (III), respectively. The central part of the molecule (–C—N—N=C–) is almost linear with C—N—N—C torsion angles of 179.1 (2), −169.5 (3) and 178.5 (2)° for (I), (II) and (III), respectively. In all the three crystals, the molecules form inversion dimers with R 2 2(8) ring motifs, which are further augmented by C—H...O interactions.

Antioxidant, biofilm inhibition and mutagenic activities of newly substituted fibrates

Purpose: A series of benzylidene-2-(4-bromophenoxy)-2-methyl propane hydrazides (1-10) were synthesized and assay them for their biofilm inhibition, antioxidant and mutagenic. Methods: All derivatives were prepared by condensation of various substituted benzaldehyde and acetophenones with 2-(4-bromorophenoxy)-2-methyl propane hydrazide, which was itself prepared by hydrazinolysis of ethyl-2-(4-bromophenoxy)-2-methyl propanoate and were characterized by FTIR, 1H NMR 13C NMR, mass spectrometry. They were screened for their in-vitro anti-oxidant, biofilm inhibition and mutagenicity by established methods. Results: Anti-oxidant results revealed that the electron donating group enhanced the scavenging ability of the compounds as seen in compounds 4b, 4h and 4i. In biofilm inhibition studies, all compounds were more active against Gram –ive bacterial strain when compared to gram +ive strain. The mutagenicity assay results indicate that the compound having chloro group substitution is mutagenic. Conclusion: The benzylidine compounds of 2-(4-bromophenoxy)-2-methyl hydrazide possessing electron donating substituents exhibit superior activities to the electron withdrawing group substituents.

Selective Synthesis and Photoluminescence Study of Pyrazolopyridopyridazine Diones and N-Aminopyrazolopyrrolopyridine Diones

The newly designed luminol structures of pyrazolopyridopyridazine diones and N-aminopyrazolopyrrolopyridine diones were synthesized from versatile 1,3-diaryfuropyrazolopyridine-6,8-diones, 1,3-diarylpyrazolopyrrolopyridine-6,8-diones, or 1,3-diaryl-7-methylpyrazolopyrrolopyridine-6,8-diones with hydrazine monohydrate. Photoluminescent and solvatofluorism properties containing UV–Vis absorption, emission spectra, and quantum yield (Φf) study of pyrazolopyridopyridazine diones and N-aminopyrazolopyrrolopyridine diones were also studied. Generally, most of pyrazolopyrrolopyridine-6,8-diones 6 exhibited the significant fluorescence intensity and the substituent effect when compared with N-aminopyrazolopyrrolopyridine diones, particularly for 6c and 6j with a m-chloro group. Additionally, the fluorescence intensity of 6j was significantly promoted due to the suitable conjugation conformation. Based on the quantum yield (Φf) study, the value of compound 6j (0.140) with planar structural skeletal was similar to that of standard luminol (1, 0.175).

Biotransformation of chlorothalonil by strain Stenotrophomonas acidaminiphila BJ1 isolated from farmland soil

Chlorothalonil is a widely used fungicide, but the contamination of soil and water environments by this chemical causes potential threats to biodiversity. Given the metabolic potential of soil microorganisms, there is a need for developing microbiological approaches to degrade persistent compounds, such as chlorothalonil, in contaminated sites. Here in this study, we isolated a bacterial strain (namely, BJ1) capable of degrading chlorothalonil from a chlorothalonil-contaminated farmland soil in the Shandong Province, China. Using 16S rDNA gene sequencing, morphological and biological characteristics, we identified the strain BJ1 as Stenotrophomonas acidaminiphila . The strain BJ1 uses chlorothalonil as a sole carbon source. At initial concentrations of 50, 100, 200 and 300 mg l −1 , it degraded 91.5%, 89.4%, 86.5% and 83.5% of chlorothalonil after 96 h of inoculation under optimum conditions (30°C and pH 7.0). Two metabolites, methyl-2,5,6-trichloro-3-cyano-4-methoxy-benzoate and methyl-3-cyano-2,4,5,6-tetrachlorobenzoate, were detected and identified based on HPLC–MS analysis, which suggests that the strain BJ1 metabolized chlorothalonil through the hydroxylation of chloro-group and hydration of cyano-group. The results of this study highlight the great potential for this bacterium to be used in chlorothalonil pollution remediation.

Glacial Acetic Acid Catalyzed Synthesis, Physicochemical and Biological Evaluation of Benzodiazepines as Potent CNS Agents

Background: Approach for green chemistry for chemical synthesis is found to be very efficient as it makes the reaction more easily, less tedious, maximize desired products and minimize by-products. Materials & Methods: Utilizing this approach 1, 5-benzodiazepines and its derivatives have been synthesized and evaluated for skeletal muscle and antianxiety activity. 1, 5-benzodiazepine derivatives have attracted great attention due to its diversity of pharmacological activities and its application in heterocyclic synthesis and medicines. The target compounds were synthesized by first reacting o-phenylenediamine with acetophenone to yield 1, 5-benzodiazepines. In the next step the NH of 1, 5-benzodiazepines were chloroacetylated and then the chloro group was substituted with different anilines. The structures were confirmed on the basis of their TLC, IR, 1H NMR and CHN elemental studies. The physicochemical parameters were determined for BBB penetration through online software. Results: The Log P values of the compounds tested showed that compounds have the potential to be CNS active. The compounds were evaluated for the skeletal muscle relaxant activity and antianxiety activity. It was investigated that 1, 5-benzodiazepines derivatives possess significant differences between control group and treated group. Conclusion: Among these derivatives, the compound bearing chloro group possesses the highest skeletal muscle relaxant and antianxiety activity.

Synthesis of a Fluorescent Whitening Molecule and its Application to Wool Fibres

Aim and Objective: Reactive dye molecules are commonly employed to dye or modify colour characteristics of wool fibres. Yellowness of wool fibres poses a challenge and here, we report synthesis of a reactive fluorescent molecule and its application to wool fibres to reduce yellowness of the wool fibre and improve its colour features. Material and Methods: The new molecule was based upon 7-amino-4-methylcoumarin (AMC) and 2,4,6- trichloro-1,3,5-triazine (TZT). The synthesis involved a two-step chemical reaction, initiated by the nucleophilic substitution of a chloro group on the triazine ring with the hydroxyl group of 4-hydroxybenzenesulfonic acid. The substitution of 2nd chloro group at triazine ring with the amino group of 7-amino-4-methylcoumarin resulted in a novel molecule with a monofunctional reactive chloro group (AMC-MCT molecule). Results: The new molecule was applied to the wool fibres using exhaust dyeing method. This exhibited a high exhaustion value; however low fixation and total efficiency values were observed for the new molecule. The resultant wool fibres exhibited fluorescence which shows that aminocoumarin fluorophore retained its fluorescence when incorporated in the new molecule. An assessment of the molecule for yellowness index in a controlled exposure to UV radiation suggested an improvement in whiteness of wool fibre. Conclusion: A novel aminocoumarin based fluorescent whitening molecule 2 has been synthesised and applied to the wool fibres. The new molecule continued to exhibit fluorescence after its application to the wool fibres. These results will encourage researchers to explore further possibilities for reactive whitening agent for wool fibres.

Selective Preparation of C 2v -Symmetric Hexaphenylbenzene Derivatives through Sequential Suzuki Coupling

We have developed effective reaction conditions for the ­Suzuki cross-coupling of chlorinated hexaphenylbenzene derivatives. A chloro group on a hexaphenylbenzene framework exhibits a low reactivity to Suzuki cross-coupling, and only nickel catalysts bearing alkyl-substituted phosphine ligands achieved the coupling. With this as a key step, we succeeded in the selective preparation of a C 2v -symmetric hexaphenylbenzene derivative containing two kinds of aryl group.