Abstract:A simple preparation of sodium impregnated on activated chicken eggshells (Na-ACE) as a solid base material for substituted chalcones synthesis is presented. After characterization using FTIR, XRD, SEM, EDS and total basicity, the catalyst was applied in Aldol condensation to produce corresponding chalcones 3a-3j. Confirmation of products structure has been done by FTIR, UV-Vis and MS instruments. Reaction can be carried out in relative short time with ethanol as the best solvent and gave the highest yield of … Show more
“…The lowest yields were obtained with 2-bromobenzaldehyde 4f and 3,4,5-trimethoxybenzaldehyde 4 h as substrates. Low yields of chalcones with benzaldehydes containing a methoxy group in the substrate are documented in the literature [ 13 ]. Fig.…”
Background
Malaria remains the major health problem responsible for many mortality and morbidity in developing countries. Because of the development of resistance by Plasmodium species, searching effective antimalarial agents becomes increasingly important. Pinocembrin is a flavanone previously isolated as the most active antiplasmodial compound from the leaves of Dodonaea angustifolia. For a better understanding of the antiplasmodial activity, the synthesis of pinocembrin and a great number of analogs was undertaken.
Methods
Chalcones 5a-r were synthesized via Claisen-Schmidt condensation using 2,4-dibenzyloxy-6-hydroxyacetophenone and aromatic aldehydes as substrates under basic conditions. Cyclization of compounds 5a-r to the corresponding dibenzylated pinocembrin analogs 6a-r was achieved using NaOAc in EtOH under reflux. Catalytic hydrogenation using 10% Pd/C as catalyst in an H-Cube Pro was used for debenzylation to deliver 7a-l. The structures of the synthesized compounds were characterized using various physical and spectroscopic methods, including mp, UV, IR, NMR, MS and HRMS. The synthesized dibenzylated flavanones 6a-d, 6i and 7a were evaluated for their in vivo antiplasmodial activities against Plasmodium berghei infected mice. Molecular docking simulation and drug likeness properties of compounds 7a-l were assessed using AutoDock Vina and SwissADME, respectively.
Results
A series of chalcones 5a-r has been synthesized in yields ranging from 46 to 98%. Treatment of the chalcones 5a-r with NaOAc refluxing in EtOH afforded the dibenzylated pinocembrin analogs 6a-r with yields up to 54%. Deprotection of the dibenzylated pinocembrin analogs delivered the products 7a-l in yields ranging from 78 to 94%. The dibenzylated analogs of pinocembrin displayed percent inhibition of parastaemia in the range between 17.4 and 87.2% at 30 mg/kg body weight. The parastaemia inhibition of 87.2 and 55.6% was obtained on treatment of the infected mice with pinocembrin (7a) and 4’-chloro-5,7-dibenzylpinocembrin (6e), respectively. The mean survival times of those infected mice treated with these two compounds were beyond 14 days indicating that the samples suppressed P. berghei and reduced the overall pathogenic effect of the parasite. The molecular docking analysis of the chloro derivatives of pinocembrin revealed that compounds 7a-l show docking affinities ranging from – 8.1 to – 8.4 kcal/mol while it was -7.2 kcal/mol for chloroquine.
Conclusion
Pinocembrin (7a) and 4’-chloro-5,7-dibenzyloxyflavanone (6e) displayed good antiplasmodial activity. The in silico docking simulation against P. falciparum dihydrofolate reductase-thymidylate synthase revealed that pinocembrin (7a) and its chloro analogs 7a-l showed better binding affinity compared with chloroquine that was used as a standard drug. This is in agreement with the drug-like properties of compounds 7a-l which fulfill Lipinski's rule of five with zero violations. Therefore, pinocembrin and its chloro analogs could serve as lead compounds for further antiplasmodial drug development.
“…The lowest yields were obtained with 2-bromobenzaldehyde 4f and 3,4,5-trimethoxybenzaldehyde 4 h as substrates. Low yields of chalcones with benzaldehydes containing a methoxy group in the substrate are documented in the literature [ 13 ]. Fig.…”
Background
Malaria remains the major health problem responsible for many mortality and morbidity in developing countries. Because of the development of resistance by Plasmodium species, searching effective antimalarial agents becomes increasingly important. Pinocembrin is a flavanone previously isolated as the most active antiplasmodial compound from the leaves of Dodonaea angustifolia. For a better understanding of the antiplasmodial activity, the synthesis of pinocembrin and a great number of analogs was undertaken.
Methods
Chalcones 5a-r were synthesized via Claisen-Schmidt condensation using 2,4-dibenzyloxy-6-hydroxyacetophenone and aromatic aldehydes as substrates under basic conditions. Cyclization of compounds 5a-r to the corresponding dibenzylated pinocembrin analogs 6a-r was achieved using NaOAc in EtOH under reflux. Catalytic hydrogenation using 10% Pd/C as catalyst in an H-Cube Pro was used for debenzylation to deliver 7a-l. The structures of the synthesized compounds were characterized using various physical and spectroscopic methods, including mp, UV, IR, NMR, MS and HRMS. The synthesized dibenzylated flavanones 6a-d, 6i and 7a were evaluated for their in vivo antiplasmodial activities against Plasmodium berghei infected mice. Molecular docking simulation and drug likeness properties of compounds 7a-l were assessed using AutoDock Vina and SwissADME, respectively.
Results
A series of chalcones 5a-r has been synthesized in yields ranging from 46 to 98%. Treatment of the chalcones 5a-r with NaOAc refluxing in EtOH afforded the dibenzylated pinocembrin analogs 6a-r with yields up to 54%. Deprotection of the dibenzylated pinocembrin analogs delivered the products 7a-l in yields ranging from 78 to 94%. The dibenzylated analogs of pinocembrin displayed percent inhibition of parastaemia in the range between 17.4 and 87.2% at 30 mg/kg body weight. The parastaemia inhibition of 87.2 and 55.6% was obtained on treatment of the infected mice with pinocembrin (7a) and 4’-chloro-5,7-dibenzylpinocembrin (6e), respectively. The mean survival times of those infected mice treated with these two compounds were beyond 14 days indicating that the samples suppressed P. berghei and reduced the overall pathogenic effect of the parasite. The molecular docking analysis of the chloro derivatives of pinocembrin revealed that compounds 7a-l show docking affinities ranging from – 8.1 to – 8.4 kcal/mol while it was -7.2 kcal/mol for chloroquine.
Conclusion
Pinocembrin (7a) and 4’-chloro-5,7-dibenzyloxyflavanone (6e) displayed good antiplasmodial activity. The in silico docking simulation against P. falciparum dihydrofolate reductase-thymidylate synthase revealed that pinocembrin (7a) and its chloro analogs 7a-l showed better binding affinity compared with chloroquine that was used as a standard drug. This is in agreement with the drug-like properties of compounds 7a-l which fulfill Lipinski's rule of five with zero violations. Therefore, pinocembrin and its chloro analogs could serve as lead compounds for further antiplasmodial drug development.
“…In the IR spectrum of the chicken eggshell sample, a broad peak around 3500-3200 cm -1 suggests the presence of -OH vibration from residual water in chicken eggshell. 7 Peaks around 1380 cm -1 and 825 cm -1 indicate the existence of nitrate ions in KNO3/ACE sample. 15 The narrow band at 3650 cm -1 is ascribed to the -OH stretching vibration.…”
Section: Catalyst Characterizationmentioning
confidence: 97%
“…ACE was prepared based on literature. 7 Chicken eggshells waste was crushed into rough powder, then it was washed sequentially with water and acetone to remove inorganic and organic impurities. After that, it was dried in an oven at 120 o C for 2 h. Dried eggshells waste was calcined at 900 o C for 4 h to produce ACE as white solid.…”
Section: Preparation Of Kno3/acementioning
confidence: 99%
“…On the other hand, the demand for a cost-effective and active catalyst in various organic transformation is still highly necessitated, and it is shifted from homogeneous to the heterogeneous system. 7 Activated chicken eggshell(ACE) constitutes one of the highly applicable CaO-based catalysts in synthetic organic chemistry. Aldol condensation, transesterification in biodiesel production, and Schiff base formation have been reported to be catalyzed using ACE.…”
Potassium nitrate impregnated on activated chicken eggshell (KNO3/ACE) was successfully prepared, and then it was characterized by means of IR, XRD, FESEM and EDAX spectroscopy. The KNO3/ACE showed high activity for the synthesis of chalcone compound, (2E,4E)-1,5-diphenylpenta-2,4-dien-1-one (3) from the reaction between acetophenone (1) and cinnamaldehyde (2). The highest yield of compound 3 was achieved up to 93% after reaction at 60 o C for 2 h in the presence of 15 wt% catalyst. Then, compound 3 was further treated with hydrazine hydrate (4) to produce (E)-3-phenyl-5-styryl-1H-pyrazole (5) up to 97% yield using the same optimized condition as in chalcone synthesis.
“…[1][2][3][4][5] They denoted remarkable biological advantages such as anticancer, anti-inflammatory, antioxidant, antimalarial, antitubercular and antimicrobial activities. [6][7][8][9][10][11] Generally, chalcones are produced by using base catalysts via Claisen-Schmidt Aldol condensation.…”
Solid catalyst of Ca@Al-Bentonite was prepared by modifying natural bentonite which collected from Bogor, Indonesia via pillarization of Al and wet impregnation of Ca particles. The catalyst was characterized by means of FTIR, XRD, XRF and BET surface area. The catalyst is successful to use for Aldol condensation in chalcone synthesis.
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