Synthesis, Activity Test and Molecular Docking of Novel Nitrophenylcalix[4]-2-methylresorcinarene Derivatives as Antimalarial Agent

This research involved the synthesis, antimalarial assay and molecular docking of novel nitrophenylcalix[4]-2-methylresorcinarene derivatives. Calix[4]-2-methylresorcinarene derivatives, i.e., 2N, 3N and 4N, were synthesized in a one-step reaction through the cyclo-condensation reaction between resorcinol and aldehydes, i.e., 2-nitrobenzaldehyde, 3-nitrobenzaldehyde and 4-nitrobenzaldehyde, respectively. The reaction was carried out through the reflux method with ethanol and hydrochloric acid 37% as the solvent and catalyst, respectively. The synthetic products were characterized using FTIR, 1H-NMR, 13C-NMR, and LC-MS spectrometers. Furthermore, the in vitro antimalarial assay was carried out against Plasmodium falciparum strain 3D7. The results showed that the 2N, 3N and 4N compounds were successfully synthesized in 86.4, 78.6 dan 95.7% yield, respectively. The antimalarial activity test of 2N, 3N and 4N gave IC50 values of 2.35, 1.68 and 1.79 µM, therefore, these compounds are classified as active antimalarial agents. Molecular docking performed against the PfLDH receptor showed that the 2N, 3N and 4N compounds had negative binding affinity values of -5.1, -6.1, and -6.0 kcal/mol and had specific interactions in the form of hydrogen bonds to the amino acid residues Arg109, Thr101 and Lys102 in the active site of the receptor. The molecular docking results agreed with the experimental antimalarial assay demonstrating the mechanism of action of nitrophenylcalix[4]-2-methylresorcinarenes as active antimalarial agents happened through the inhibition of the PfLDH receptor

Sonochemical and Mechanochemical Synthesis of Alcohols from Aldehydes and Ketones

A green, convenient, and scalable synthesis of alcohols through the reduction of aldehydes and ketones has been developed. The green reduction was conducted using two different methods, namely sonochemistry and mechanochemistry. In the former method, the solution of aldehydes or ketones and sodium borohydride was irradiated under ultrasound irradiation. In the latter technique, the reaction mixture was ground under solvent-free conditions. The reduction reaction was performed at room temperature and completed in only 10 min using both protocols. The results showed that aldehydes and ketones with aromatic, heteroaromatic, and aliphatic motifs were tolerated under the reaction conditions, allowing the formation of the corresponding alcohols with the synthetic yields of 75–98% and 77–95% for grinding and sonication methods, respectively. In addition, the reaction can be carried out on a multigram scale

SYNTHESISOF FLAVANONE-6-CARBOXYLICACID DERIVATIVES FROMSALICYLIC ACID DERIVATIVE

Synthesis of fIavanone-6-carboxylic acid derivatives had been conducted via the route of chalcone. The synthesis was carried out from salicylic acid derivative, i.e. 4-hydroxybenzoic acid, via esterification, Fries rearrangement, Claisen-Schmidt condensation and 1,4-nucleophilic addition reactions. Structure elucidation of products was performed using FT-IR, 1H-NMR, GC-MS and UV-Vis spectrometers. Reaction of 4-hydroxybenzoic acid with methanol catalyzed with sulfuric acid produced methyl 4-hydroxybenzoate in 87% yield. The acidcatalyzed- acetylation of the product using acetic anhydride gave methyl 4-acetoxybenzoate in 75% yield. Furthermore, solvent-free Fries rearrangement of methyl 4-acetoxybenzoate in the presence of AIC/3produced 3- acetyl-4-hydroxybenzoicacid as the acetophenonederivatives in 67%yield. Then, Claisen-Schmidtcondensation of the acetophenone and benzaldehyde derivatives of p-anisaldehyde and veratraldehydein basic condition gave 2\u27- hydroxychalcone- 5\u27-carboxylicacid derivatives in 81 and 71 %yield, respectively. Finally, the ring closure reaction of the chalconeyielded the co"esponding fIavanone-6-carboxylicacids in 67 and 59%yield, respectively

PREPARATION AND APPLICATION OF 2-METHOXYPHENYLCALIX[ 4]RESORCINARENE TRIPHENYLPHOSPHONIUM CHLORIDE IMMOBILIZED ON ALGINATE TO REMOVE HEXAVALENT CHROMIUM

Synthesis of positively-charged 2-methoxyphenylcalix[4]resorcinarene triphenylphosphonium chloride has been conducted. The synthesis was carried out from salicylaldehyde via methylation, aromatic electrophilic substitution-cyclization, chloromethylation and bimolecular nucleophilic substitution reactions. Structural elucidation of products was performed using FT-IR spectrophotometer, NMR, GC-MS and MS spectrometers. The synthesized calix[4]resorcinarene was then immobilized on the alginate matrix. The immobilized material was characterized using FT-IR spectrophotometer. The three adsorbents of positively-charged calix[4]resorcinarene C, alginate A, and calix[4]resorcinarenealginate CA 1% were then applied in the removal of hexavalent chromium. Adsorption parameters including pH, kinetic and equilibrium parameters were also determined. Reaction of salicylaldehyde with dimethyl sulphate (DMS) catalyzed by NaOH was performed by refluxing the mixture for 4 hours and gave 2-methoxybenzaldehyde in 93% yield. The aromatic electrophilic substitution-cyclization of methylation product and resorcinol in the presence of HCl gave 2-methoxyphenylcalix[4]resorcinarene in 86% yield. Chloromethylation of calix[4]resorcinarene using paraformaldehyde, ZnCl2, HCl in N,Ndimethylformamide (DMF) produced chloromethylated calix[4]resorcinarene (88% yield), which was then reacted with triphenylphosphine to give positively-charged 2- methoxyphenylcalix[4]resorcinarene triphenylphosphonium chloride in 88% yield. Preparation of alginate and calix[4]resorcinarene-alginate gel beads was performed using calcium chloride solution and produced transparent (diameter of 2.2 mm/bead) and orange (2.4 mm) beads, respectively. The IR analysis showed that immobilized calix[4]resorcinarene had similar functional group with free calix[4]resorcinarene. Adsorption of Cr(VI) on calix[4]resorcinarene, alginate and immobilized calix[4]resorcinarene on alginate was optimum at pH 3 and reached the equilibrium time at 8, 2 and 8 hours, respectively. Furthermore, the pseudo second-order kinetic model of Ho could satisfactorily describe the adsorption process, where the intraparticle and liquid film diffusions might govern the adsorption mechanism. Adsorption of Cr(VI) on calix[4]resorcinarene, and immobilized calix[4]resorcinarene on alginate with the capacities of 81.301 and 21.739 mg/g, could be classified as chemisorption and correlated well with the Langmuir model, while that on alginate with the capacity of 12.870 mg/g, could be considered as physical adsorption and fitted with Freundlich model. The immobilization of calix[4]resorcinarene on alginate matrix might reduce capacity of calix[4]resorcinarene and increase the capacity of alginate. The material seemed to be more applicable in the industrial and environmental applications as it was easily collected and had adequate particle size

Strategies To Access γ-Hydroxy-γ-butyrolactams

α,β-Unsaturated γ-hydroxy-γ-butyrolactams are of a great interest due to their presence in designed pharmaceutical molecules and numerous natural products displaying a broad spectrum of biological activities. In addition, these five-membered heterocyclic compounds are also relevant and versatile building blocks in organic synthesis. In this context, strategies for the construction of these scaffolds has triggered considerable attention and this review highlights the progress in the formation of α,β-unsaturated γ-hydroxy-γ-butyrolactams (5-hydroxy-1,5-dihydro-2H-pyrrol-2-ones)

Synthesis of Vanillin-Azine as Colorimetric Chemosensor of Sulfide Anion

Vanillin-azine (VA), (4,4'-((1E,1'E)-hydrazine-1,2-diylidenebis(methanelylidene))bis(2-methoxyphenol) has been synthesized from vanillin and tested as anion colorimetric chemosensors for sulfide anion. The VA was obtained from a condensation reaction between vanillin and hydrazine hydrate with a mol ratio of 2:1 mol for 24 h at room temperature. The structure was elucidated using FTIR, GC-MS, 1 H-NMR, and 13CNMR spectrometers. The VA compound was examined as a colorimetric chemosensor for sulfide anion over several anions of CN−, F−, Cl−, Br−, I−, N3 −, CH3COO−, and NO3 −. The structure of the product showed agreement with all spectrometric data. The VA chemosensor tests indicated only selective to S2− anion followed by a color change from colorless to light blue in a DMF:HEPES buffer solution (DMF:HBS) medium (9:1, v/v, 10 mM, pH = 7.4). Filter paper strips can detect S2− anion with a color change from white to yellow. The VA chemosensor has a limit of detection (LOD) of 5.4 × 10−4 M, therefore, the VA chemosensor can be applied to detect S2− anion in tap water

Copper(I)-Catalysed Multicomponent Reaction: Straightforward Access to 5-Hydroxy-1H-pyrrol-2(5H)-ones

International audienceA copper-catalysed multicomponent coupling reaction between readily available (Z)-3-io-doacrylic acids, terminal alkynes, and primary amines was developed to smoothly access a small library of 5-hydroxy-1H-pyrrol-2(5H)-ones in good yields. This practical and general process was applied to a short-steps synthesis of the natural product pulchellalactam

Synthesis and Heme Polymerization Inhibitory Activity (HPIA) Assay of Antiplasmodium of (1)-N-(3,4-Dimethoxybenzyl)-1,10-Phenanthrolinium Bromide from Vanillin

The synthesis of (1)-N-(3,4-dimethoxy-benzyl)-1,10-phenanthrolinium bromide had been conducted from vanillin. Heme polymerization inhibitory activity assay of the synthesized antiplasmodium has also been carried out. The first step of reaction was methylation of vanillin using dimethylsulfate and NaOH. The mixture was refluxed for 2 h to yield veratraldehyde in the form of light yellow solid (79% yield). Methylation product was reduced using sodium borohydride (NaBH4) with grinding method and yielded veratryl alcohol in the form of yellow liquid (98% yield). Veratryl alcohol was brominated using PBr3 to yield yellowish black liquid (85% yield). The final step was benzylation of 1,10-phenanthroline monohydrate with the synthesized veratryl bromide under reflux condition in acetone for 14 h to afford (1)-N-(3,4-dimethoxy-benzyl)-1,10-phenanthrolinium bromide (84%) as yellow solid with melting point of 166-177 °C. The structures of products were characterized by FT-IR, GC-MS and 1H-NMR spectrometers. The results of heme polymerization inhibitory activity assay of (1)-N-(3,4-dimethoxybenzyl)-1,10-phenanthrolinium bromide showed that it had IC50 HPIA of 3.63 mM, while chloroquine had IC50 of4.37 mM. These results indicated that (1)-N-(3,4-dimethoxybenzyl)-1,10-phenanthrolinium bromide was more potential antiplasmodium than chloroquine

Fe/ZSM-5-catalyzed-synthesis of 1,4-dihydropyridines under ultrasound irradiation and their antioxidant activities

A small library of 1,4-dihydropyridines have been synthesized from ethyl acetoacetate, ammonium acetate and various aldehydes via Hantzsch multicomponent reaction in the presence of Fe/ZSM-5 catalyst under ultrasound irradiation for 90 min. 1,4-Dihydropyridine derivatives were obtained in 64-86% yields and the heterogeneous Fe/ZSM-5 catalyst can be employed for four reaction cycles without losing the catalytic activity. All products were evaluated for their antioxidant activities using the DPPH method and compound 4g was found to be an effective antioxidant agent with DPPH activity of 83.5%

SYNTHESIS OF FLAVANONE-6-CARBOXYLIC ACID DERIVATIVES FROM SALICYLIC ACID DERIVATIVE

Synthesis of flavanone-6-carboxylic acid derivatives had been conducted via the route of chalcone. The synthesis was carried out from salicylic acid derivative, i.e. 4-hydroxybenzoic acid, via esterification, Fries rearrangement, Claisen-Schmidt condensation and 1,4-nucleophilic addition reactions. Structure elucidation of products was performed using FT-IR, 1H-NMR, GC-MS and UV-Vis spectrometers. Reaction of 4-hydroxybenzoic acid with methanol catalyzed with sulfuric acid produced methyl 4-hydroxybenzoate in 87% yield. The acid-catalyzed-acetylation of the product using acetic anhydride gave methyl 4-acetoxybenzoate in 75% yield. Furthermore, solvent-free Fries rearrangement of methyl 4-acetoxybenzoate in the presence of AlCl3 produced 3-acetyl-4-hydroxybenzoic acid as the acetophenone derivatives in 67% yield. Then, Claisen-Schmidt condensation of the acetophenone and benzaldehyde derivatives of p-anisaldehyde and veratraldehyde in basic condition gave 2'-hydroxychalcone-5'-carboxylic acid derivatives  in 81 and 71 % yield, respectively. Finally, the ring closure reaction of the chalcone yielded the corresponding flavanone-6-carboxylic acids in 67 and 59% yield, respectively