Presence Of Amines Research Articles

Synthesis and antimicrobial evaluation of some novel malononitrile derivatives from N-phenylpyrrolidine-2, 5-diones under microwave irradiation

The purpose of study was to synthesize the focused library of new malononitrile derivative of substituted Nphenylpyrrolidine- 2, 5-dione as potential new hybrid antifungal molecules. These hybrid molecules were synthesized in a coupling reaction of substituted N-phenylpyrrolidine-2, 5-dione with dicyanomethane using solvent free ecofriendly microwave assisted method. The 2, 5-diones were prepared by the reaction of succinic anhydride with substituted aryl amines in presence of benzene and acetyl chloride. All the synthesized molecules were persisted and vetted for antimicrobial activities. Most of the molecules showed potential antifungal activity against Candida albicansandAspergillusniger.

Remarkable rheological properties of short alkyl chain derivatives of hyaluronic acid

Event Abstract Back to Event Remarkable rheological properties of short alkyl chain derivatives of hyaluronic acid Dalila Petta1, 2, David Eglin1, Dirk W. Grijpma2 and Matteo D'Este1 1 AO Research Institute Davos, Switzerland 2 University of Twente, Department of Biomaterials Science and Technology, Netherlands Introduction: Chemical modification of hyaluronic acid (HA) is a key aspect for the production of advanced naturally derived biomaterials. The grafting of hydrophobic moieties to HA is of particular interest to generate amphiphilic species that can self-assemble in supramolecular structures[1]. In this study, we prepared and characterized a series of short alkyl derivatives of HA with a broad range of substitution degree (DS). A novel derivatization method based on amidation promoted by 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) was used[2]. Remarkable rheological properties were observed. Materials and Methods: HA-butylamine (HA-B) and HA-propylamine (HA-P) were synthesized by reacting HA (molecular weight = 280 kDa) with the amines in presence of DMTMM in MES buffer, pH = 5.5, at different temperatures, molar ratios between reagents and multiple feeding. The molar degree of substitution (DS) was determined via 1H NMR (Bruker Avance AV-500 18 MHz spectrometer). Flow and oscillatory rheological measurements were performed for 5% v/w solutions of HA-B and HA-P with an Anton Paar MCR-302 rheometer. As some derivatives were non-soluble, a thermal treatment (92°C for 1h 30', sufficient to make them soluble) was applied to all specimens before characterization. Absence of free amine groups in the final product was assessed via Ninhydrin assay. Results: Synthesis. At higher temperature, DMTMM was deactivated faster. Also the coupling proceeded faster, with overall yield increase (fig 1). DS of up to 51% was achieved with multiple amine additions. Rheological properties. Storage modulus G' increased with the increase of DS up to a maximum at DS = 3.7% (HA-B) and 3% (HA-P), and decreased for higher DS (fig 2). Similar behavior was observed for the viscosity curve (not shown), with maximum zero-shear viscosity and shear-thinning gradient for the DS above indicated. Fig. 1: Kinetics of HA-P formation at 56°C and at room temperature (RT), also upon multiple amine additions (empty squares). Fig. 2: G' at RT versus DS (ratio HA:DMTMM: amine 1:1:0.5). Discussion: A broad range of HA modifications with grafted short alkyl groups was achieved. Upon changing the DS values, remarkable changes in the rheological properties were observed. The complex dependence of G' on DS suggests a structural rearrangement with associative behaviour maximized at DS= 3.7% (HA-B) and 3% (HA-P). The non-solubility of most as-prepared derivatives before thermal treatment supports this hypothesis. At the moment, deeper structural analyses are ongoing. Conclusion: The DMTMM grafting strategy introduced here is a viable method for fine-tuning the rheological properties of HA with minimal modification of the polymer. Synthesis conditions were optimized, resulting in superior efficiency at high temperature despite faster DMTMM deactivation. Owing to their singular rheological profile, HA-B and HA-P are valuable biomaterial candidates for preparing bio-inks or hydrogels for drug delivery and regenerative medicine. Ms. Doris Sutter from ETH-Zurich, for performing NMR measurements

Synthesis, Molecular Docking and Biological Evaluation of Substituted Quinazolinones as Antibacterial Agents

A series of 7-chloro-2,3-disubstituted-4(3H)-quinazolinones (4a-j) were synthesized by the reaction of 3-amino-7-chloro-2-phenylquinazolin-4(3H)-one (3) with various amines in presence of formaldehyde. The starting material for the compounds was 2-amino-4-chloro benzoic acid. The structures of the compounds were characterized by IR, 1 H NMR, elemental analyses. Docking analysis of quinazolinone derivatives was done with DNA gyrase protein which was carried out by means of the AutoDockTools (ADT) v 1.5.4 and AutoDock v 4.2 programs. All compounds interacted with DNA gyrase protein. Preclinical evaluation of the compounds was ascertained by in silico toxicity, blood-brain barrier and drug like properties. All compounds were investigated for their antibacterial activity. Overall, compound (4b) showed better properties as a drug like candidate.

Synthesis and Characterization of Polysialic Acid–Uricase Conjugates for the Treatment of Hyperuricemia

Uricase, an enzyme used for the treatment of hyperuricemia, is conjugated with polysialic acid (PSA) of average molecular weight of 10 kDa by reductive amination in presence of NaCNBH3 in order to improve its pharmacological properties. Polysialylation with 50-,100-,150- and 200-fold molar excess of PSA increased the percentage substitution of the free amino groups on enzyme surface (46, 66, 78 and 80 % respectively). The SDS-PAGE is used to visualize the conjugates with increased molecular weight and it retained almost 65 % of their initial specific activity after conjugation. The stability studies at physiological condition reveals improved stability and activity than the native enzyme. The apparent KM of the enzyme has increased slightly from 4.18 × 10−5 M to 5.46 × 10−5 M suggesting that the affinity of the substrate to the enzyme has not been altered to a higher extent. The conjugates, when probed against anti-uricase antibodies generated in rabbit, showed a clean decline in the affinity by 35 % and also have retained double the catalytic activity than that of the native enzyme after exposure to antiserum. The results suggest that uricase-PSA conjugates can be used as an alternative to the conventional synthetic polymer-enzyme conjugates.

Synthesis and antimicrobial evaluation of amide derivatives of benzodifuran-2-carboxylic acid

We have synthesized various amide derivatives of benzodifuran-2-carboxylic acid from resorcinol. Reaction of 7-hydroxy-4-methylcoumarin with chloroacetone in anhydrous K2CO3 and dry acetone gave ether derivative of 7-hydroxy-4-methylcoumarin 3 which on reaction with N-bromosuccinimide in chloroform gave corresponding 3-bromo derivative 4. Cyclization of bromo derivative in 10% ethanolic KOH gave benzodifuran-2-carboxylic acid 5. This acid was converted into acid chloride using oxalyl chloride and then substituted with different amines in presence of base, triethylamine to give amide derivatives of benzodifuran-2-carboxylic acid 6. All compounds were screened for antimicrobial activity against two Gram positive bacteria Staphylococus aureus and Bacillus subtilis, two Gram negative bacteria E. coli and P. aeruginosa and one fungus Candida albicans.

ChemInform Abstract: Synthesis of 6‐Aminopropyl‐6H‐indolo[2,3‐b]quinoxaline Derivatives.

A series of 6-(3-aminopropyl)-6H-indolo[2,3-b]quinoxalines were synthesized with high yields by the reaction of 6-(3-chloropropyl)-6H-indolo[2,3-b]quinoxaline and corresponding amines in presence of tetrabutylammonium iodide in boiling toluene or dimethylformamide at room temperature. It was found that boiling of 6-(3-chloropropyl)-6H-indolo[2,3-b]quinoxaline in acetone with sodium iodide or in acetic acid lead to intramolecular cyclization product.

Synthesis, In Vitro Evaluation of Some Novel Quinazolin-4(3H)-one Derivatives as Anti-Tumor Agents

In an effort to develop anticancer agents, a series of Mannich bases were prepared by Mannich reaction. When one biologically active molecule is linked to another, the resultant molecule generally has increased potency. Hence two pharmacophores, i.e. quinazoline ring and amine moiety are fused to obtain highly potent, more specific and less toxic agent. In the present study, synthesis of novel quinazolin-4(3H)-one derivatives by condensation of appropriate quinazolines with various p- substituted primary amines in presence of glacial acetic acid and ethanol at room temperature (Mannich reaction). Synthesized compounds were characterized; both analytical and spectral data (UV, IR, GC-MS, 1 H NMR) of all derivatives were in full agreement with proposed structures. All the derivatives were tested for their anti-tumor activity by two in vitro studies like Brine shrimp Lethality assay and Trypan blue exclusion assay.

Synthesis of 6‐Aminopropyl‐6H‐indolo[2,3‐b]quinoxaline Derivatives

A series of 6‐(3‐aminopropyl)‐6H‐indolo[2,3‐b]quinoxalines were synthesized with high yields by the reaction of 6‐(3‐chloropropyl)‐6H‐indolo[2,3‐b]quinoxaline and corresponding amines in presence of tetrabutylammonium iodide in boiling toluene or dimethylformamide at room temperature. It was found that boiling of 6‐(3‐chloropropyl)‐6H‐indolo[2,3‐b]quinoxaline in acetone with sodium iodide or in acetic acid lead to intramolecular cyclization product.

Ruthenium catalysed one-pot synthesis of S-allyl and cinnamyl dithiocarbamates using allyl and cinnamyl acetates in water

A convenient and efficient procedure for the synthesis of S-allyl/cinnamyl dithiocarbamates has been developed by a one-pot reaction of allyl/cinnamyl acetate, carbon disulfide and amine in presence of Ru(acac)3 in water. A variety of functionalized dithiocarbamates have been obtained by this procedure in high yields. The reaction proceeds via a catalytic Ru(II) species, generated in situ during the reaction.

Carbon surface derivatization by electrochemical reduction of a diazonium salt in situ produced from the nitro precursor

Two different surface derivation procedures have been used to modify glassy carbon electrodes based on the electrochemical reduction of diazonium cations in situ generated from the nitro precursor. The first sequential procedure completely reduces the nitro group into the corresponding amine, which is further diazotized in situ. This unique sequential procedure allows surface derivatization by species having extended conjugation as illustrated by the use of a p-nitrophenylethynyl benzene precursor. The second concerted procedure yields the diazonium cation in situ by the conversion of the nitro group into the corresponding amine in presence of all reagents required for the diazotization reaction. The major advantage of this “one-pot” procedure is that the diazonium cation is generated locally in close proximity to the electrode surface by rapid diazotization of the electrogenerated amine. The in situ production of diazonium cations and subsequent surface attachment is monitored using a p-nitrophenylethynyl benzene precursor bearing a catechol group. Surface coverages are determined from the cyclic voltammograms of the surface-confined catechol groups. A comparative study of the surface coverage values obtained for redox surfaces prepared with different conditions, allows optimization of the “one pot” procedure, leading to an efficient surface modification.

Enantioselective one-pot three-component synthesis of propargylamines catalyzed by copper(I)–pyridine bis-(oxazoline) complexes

A one-pot three-component coupling of aldehydes and amines in presence of terminal alkynes has been efficiently catalyzed by copper (I) complex of i-Pr-pybox-diPh 2b or s-Bu-pybox-diPh 2c. The process is simple and allows the synthesis of various propargylamines in good to excellent enantioselectivities (up to 99% ee) and in higher yields. The nature of the substituents attached to imines plays a vital role on the enantioselectivities obtained. The presence of gem-diphenyl group at C-5 position and secondary alkyl substituents at the C-4 chiral center of the oxazoline rings of the chiral ligands was found to be crucial for higher enantioselectivities. A transition state model involving π–π stacking is also proposed for the stereochemical outcome.

Synthesis and In‐vitro Antimicrobial Activity of Secondary and Tertiary Amines Containing 2‐Chloro‐6‐methylquinoline Moiety

A number of secondary and tertiary amines bearing 2-chloro-6-methylquinoline were synthesized by nucleophilic substitution reaction of 3-(chloromethyl)-2-chloro-6-methylquinoline with substituted aromatic primary and secondary amines in presence of catalytic amount of triethylamine (TEA) and K(2)CO(3). All the compounds were characterized by combined use of IR, (1)H-NMR, (13)C-NMR, mass spectral data, and microanalyses. The newly synthesized quinolinyl amines were screened in vitro for their antifungal activity against Aspergillus niger MTCC 281, Aspergillus flavus MTCC 277, Monascus purpureus MTCC 369, Penicillium citrinum NCIM 768 and for antibacterial activity strains viz. Escherichia coli NCTC 10418, Staphylococcus aureus NCTC 65710, and Pseudomonas aeruginosa NCTC 10662 by agar diffusion technique. Results of the preliminary screening revealed that some of the compounds mainly those with electron withdrawing groups in the phenyl ring showed promising antifungal activity.

Morpholinium bisulfate [morH][HSO4]-promoted O, S, and Nacylation at room temperature

Morpholinium bisulfate [morH][HSO4] found to be highly inexpensive, efficient, and reusable catalyst to promote the acylation of phenols, thiols, alcohols, and amines in presence of acetic anhydride under solvent-free condition with excellent yields by stirring at room temperature. Present methodology deals with remarkable features of mild reaction condition, high yielding, shorter reaction time, easy workup, and more importantly, environmentally benign.

Grafting of aminated oligogalacturonans onto Douglas fir barks. A new route for the enhancement of their lead (II) binding capacities

Chemical modification of Douglas fir bark and its subsequent utilization in adsorption of PbII from aqueous solutions was investigated. A new approach to enhance the natural properties of bark by covalent grafting of oligogalacturonans was developed. The polysaccharidic moiety of barks was functionalized by periodate oxidation and derivatized after reductive amination in presence of aminated oligogalacturonic acid. PbII adsorption isotherms of derivatized barks were then determined and compared with the capabilities of crude barks using the Langmuir adsorption model in terms of affinity ( b) and maximum binding capacities ( q max). Derivatization resulted in significant enhancements of the q max values (up to ×8), along with little change of the affinity parameter.

Synthesis of 7-substituted pyrazolo[1,5-a]pyrimidine-3-carboxamides as potential non benzodiazepine hypnotics

A variety of new pyrazolo[1,5-a]pyrimidines has been prepared as potential drugs for the treatment of insomnia. The general synthetic route used for this purpose involves the condensation of substituted cyanoacetamides 5a-c, prepared by reaction of cyanoacetic acid with amines in presence of acetic anhydride, with dimethylformamide dimethylacetal and subsequent treatment of the formed enamines 6 with hydrazine hydrate. This process affords the corresponding aminopyrazole carboxamides 9 that react with the enaminonitrile 12 to generate the targets. Structures of the substance prepared in these sequences were established by using spectroscopic methods, including N HMBC and NOE difference experiments, as well as X-raycrystallographic analysis.

Suitability of ionic liquids as mobile‐phase additives in HPLC with fluorescence and UV detection for the determination of heterocyclic aromatic amines

The effects of several ionic liquids (ILs) as mobile-phase additives in HPLC with fluorescence and UV-Vis detection for the determination of six heterocyclic aromatic amines were evaluated using two different C(18) stationary phases with moderate silanol activity. The studied ILs were 1-butyl-3-methylimidazolium tetrafluoroborate, 1-hexyl-3-methylimidazolium tetrafluoroborate and 1-methyl-3-octylimidazolium tetrafluoroborate. The optical behaviour of heterocyclic aromatic amines in presence of ILs was studied and the silanol-suppressing potency of ILs was evaluated for the two stationary phases studied. Several chromatographic parameters were evaluated in the presence or absence of ILs, or using triethylamine, the most common mobile-phase additive. The best results were achieved using 1 mM 1-butyl-3-methylimidazolium tetrafluoroborate as mobile-phase additive and NovaPak column. In these conditions and with 18% of ACN in the mobile phase, analytical performance of the chromatographic methods using fluorescence and UV-Vis were evaluated, obtaining good precision in all cases (RSD lower than 6.6%) and low LOD (0.001-0.147 microg/mL with UV-Vis and 0.001-0.006 ng/mL with fluorescence detection).

L-Proline-catalysed facile green protocol for the synthesis and antimycobacterial evaluation of [1,4]-thiazines

A series of ethyl 6-(4-chlorobenzoyl)-1,1-dioxo-3,5-diaryl-1,4-thiazinane-2-carboxylates was prepared in good yields (72–90%) from the reaction of ethyl 2-[(2-oxo-2-arylethyl)sulfonyl]acetate, substituted aromatic aldehydes and amines in presence of green catalyst, l-proline. These compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant M. tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC 2) using agar dilution method. Ethyl 6-(4-chlorobenzoyl)-3,5-di(4-nitrophenyl)-1,1-dioxo-1,4-thiazinane-2-carboxylate was found to be the most promising compound (MIC: 0.68 μM) active against MTB and MDR-TB.

Synthesis of (purin-6-yl)acetates and their transformations to 6-(2-hydroxyethyl)- and 6-(carbamoylmethyl)purines

A novel approach to the synthesis of (purin-6-yl)acetates was developed based on Pd-catalyzed cross-coupling reactions of 6-chloropurines with a Reformatsky reagent. Their reduction with NaBH4 and treatment with MnO2 gave 6-(2-hydroxyethyl)purines, while reactions with amines in presence of NaCN afforded 6-(carbamoylmethyl)purines. Mesylation of the 6-(2-hydroxyethyl)purines followed by nucleophilic substitutions gave rise to several 6-(2-substituted ethyl)purines. This methodology was successfully applied to the synthesis of substituted purine bases and nucleosides for cytostatic and antiviral activity screening. None of the compounds exerted significant activity.

Synthesis and antimicrobial activities of novel formazans incorporating pyrimidine ring

Reaction of 5-substituted-4(3H)-one-2-mercaptopyrimidines la and 1b with hydrazine hydrate furnishes 5- ' substituted-4(3H)-one-2-hydrazinopyrimidines 2a and 2b. Condensation of compounds 2a and 2b with salicylaldehyde and anisaldehyde yields 2-hydroxybenzaldehyde-(5'-substituted-4'(3'H)-one)-2'-pyrimidazolylhydrazones) 3a and 3b and 4-methoxybenzaldehyde-(5'-substituted-4'(3'H)-one)-2'-pyrimidazolylhydrazones) 3c and 3d respectively. Compounds 3a-d were reacted with diazonium salts of an appropriate primary amine in presence of base furnished the target formazans 4a-1. All the synthesized compounds were evaluated for antimicrobial activities.

Eco‐friendly Crosslinking Agent for Acid Functional Acrylic Resin

Oil from J. multifida was extracted and it was first converted into N,N‐bis(2‐hydroxyethyl) Jatropha fatty amide (HEJFA). HEJFA has been synthesized by reaction between Jatropha oil and diethanol amine in presence of zinc oxide as a catalyst. The reaction is relatively rapid and proceeded to high yield at 200±5 OC. The resulting HEJFA was used to formulate thermosetting coating compositions. Films were cured at ambient (air drying) and elevated (stove drying) temperatures using N, N‐bis(2‐hydroxyethyl) Jatropha fatty amide (HEJFA) as eco‐friendly crosslinking agent for acrylic resin. The coating performance of the various compositions was tested by measurement of scratch hardness, impact strength and chemical resistance. The results show better performance of the HEJFA based compositions compared to butylated melamine formaldehyde (MF) based compositions.