Synthesis, characterization and evaluation of antiinflammatory properties of novel α, β-unsaturated ketones

Purpose: To prepare and characterize alicyclic aromatic chalcone derivatives, and study their antibiotic and anti-inflammatory properties.Methods: Claisen-Schmidt (aldol condensation) base-catalyzed condensation was used for preparation of chalcone derivatives (compounds I - IV), and the products were characterized using ultraviolet-visible spectroscopy (UV), FT-IR spectroscopy, proton nuclear magnetic resonance (1H-NMR), carbone 13CNMR and mass spectroscopy (MS). The antibacterial effect of the compounds was determined against Baci. cereus, Staph. Aureus, E. coli, and Pseudomonas Aeruginosa. In addition, their anti-inflammatory effects were assayed using cotton granule-induced granuloma in mice. The results were compared with those for diclofenac, a standard drug. The synthesized derivatives were subjected to theoretical studies on their stabilities, and some chemical parameters were calculated using density function theory [DFT].Results: Using Claisen-Schmidt reaction, it was possible to prepare stable chalcone derivatives, such as derivatives of 2-(3-phenyl  acryloyl)cyclopentan-1-one, with good results. Depending on the substituted group, it was also shown that the derivatives had effective biological effects. Compound IV displayed a noticeable antibacterial effect against Staph. aureus and E. coli. The prepared chalcone derivatives exerted markedly variable anti-inflammatory effects.Conclusion: These results indicate that Claisen-Schmidt reaction is not limited to the preparation of chalcone derivatives from diphenyl structures  only. Stable alicyclic aromatic structures can also be used. This results in derivatives with good biological effects. Keywords: Chalcones, Claisen-Schmidt, Anti-inflammatory effects, Granuloma, Aldol Condensatio

Preparation of diethyl malonate adducts from chalcone analogs containing a thienyl ring

Nine chalcone-diethyl malonate derivatives (4a-i) were prepared by the reaction of chalcone derivatives (3a-i) with diethyl malonate in the presence of a catalytic amount of KOt-Bu in CH2CI2 in good to excellent yields. The products were characterized by FTIR, 1H-NMR, 13C-NMR and elemental analyses. KEY WORDS: Michael addition, Chalcone, KOt-Bu, Diethyl malonate  Bull. Chem. Soc. Ethiop. 2010, 24(1), 85-91. 

Cyclohexenones Through Addition of Ethyl Acetoacetate to 3-Aryl-1-(thiophen-3-yl)prop-2-en-1-one Derivatives

Chalcone derivatives 3a–i containing a thiophene ring were prepared by the condensation of 1-(thiophen-3-yl)ethanone with aromatic aldehydes in excellent yields. The Michael addition of ethyl acetoacetate 4 to chalcone derivatives 3a–i resulted in the formation of nine novel ethyl 6-aryl 4-(3-thienyl)cyclohex-3-en-2-one-1-carboxylate derivatives 6a–i.Keywords: Michael Addition, Ethyl Acetoacetate, Cyclohexenones, Cyclocondensatio

SYNTHESIS OF FLAVONES FROM 2-HYDROXY ACETOPHENONE AND AROMATIC ALDEHYDE DERIVATIVES BY CONVENTIONAL METHODS AND GREEN CHEMISTRY APPROACH

Objective: Flavones occupy a special place in the realm of natural and synthetic organic chemistry owing to their diversified biological activities. In this study, a series of chalcone derivatives were synthesized and after cyclization of chalcone to synthesized various substituted flavone derivatives (2A-2L). 2 Methods: The reaction of 2-hydroxy acetophenone with substituted aromatic aldehydes produced chalcone by trituration (NaOH) and conventional methods (KOH/EtOH), which upon further cyclization with dimethyl sulfoxide/I  resulted to form flavone derivatives.Results: The purity of compounds was ascertained by melting point and thin-layer chromatography. The synthesized compounds have been characterized by mass, infrared, and1H nuclear magnetic resonance spectral analysis.Conclusion: Based on spectral data, it was proved that all synthesized chalcones and flavones derivatives meet the standard values of various spectral techniques and further it will be evaluated for pharmacological activities.Keywords: Chalcone, Flavone, Trituration, Conventional, Claisen-Schmidt condensation

Diversity of secondary metabolites from Genus Artocarpus (Moraceae)

Abstrak. Hakim A. 2010. Keanekaragaman metabolit sekunder Genus Artocarpus (Moraceae). Nusantara Bioscience 2:146-156. Beberapa spesies dari genus Artocarpus (Moraceae) telah diteliti kandungan bahan alamnya. Metabolit sekunder yang berhasil diisolasi dari genus Artocarpus terdiri dari terpenoid, flavonoid, stilbenoid, arilbenzofuran, neolignan, dan adduct Diels-Alder. Kelompok flavonoid merupakan senyawa yang paling banyak ditemukan dari tumbuhan Artocarpus. Senyawa flavonoid yang telah berhasil diisolasi dari tumbuhan Artocarpus memiliki kerangka yang beragam seperti calkon, flavanon, flavan-3-ol, flavon sederhana, prenilflavon, oksepinoflavon, piranoflavon, dihidrobenzosanton, furanodihidrobenzosanton, piranodihidrobenzosanton, kuinonosanton, siklolopentenosanton, santonolid, dihidrosanton. Kata kunci: Artocarpus, Moraceae, flavonoid, Diels-Alder, metabolit sekunder

A comparative study on synthesis of some novel α,β-unsaturated carbonyl derivatives and their antioxidant potential

Free radicals are constantly formed in human system either as accidental products during metabolism or deliberately during the process of phagocytosis or due to environmental pollutants, ionizing radiations, ozone, heavy metal poisoning, etc. It is found from literature survey that chalcones (α,β-unsaturated carbonyl derivatives) exhibit great antioxidant activity. Hence, the synthesis of some new chalcone derivatives was undertaken and were synthesized by two methods namely, conventional and microwave irradiation methods. The synthesized chalcone derivatives were tested for their in vitro antioxidant activity by using NBT-superoxide free-radical scavenging activity and DPPH radical scavenging activity. The potency of the chalcone derivatives was estimated by IC50 values and they have shown promising antioxidant activity. Among all the chalcones synthesized, derivative 3e showed maximum superoxide inhibition as per NBT method and all the derivatives have shown different percentage inhibitions at different concentrations as per  DPPH method. The compounds were characterized by 1H NMR and IR spectral analysis

Design and synthesis of new inhibitors of p53–MDM2 interaction with a chalcone scaffold

The virtual screening of a library of chalcone derivatives led us to the identification of potential new MDM2 ligands. The chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two chalcones (3 and 4) were identified as putative small molecule inhibitors of p53–MDM2 interaction. The activity of both chalcones was further investigated in a panel of human tumor cells. Chalcones 3 and 4 revealed a pronounced tumor cell growth inhibitory effect on tumor cell lines. Additionally, chalcone 4 caused alterations in the cell cycle profile, induced apoptosis and increased the levels of p53, p21 and PUMA proteins in NCI-H460 cells. Computational docking studies allowed to predict that, like nutlin-3A (a well-known small-molecule inhibitor of p53–MDM2 interaction), chalcones 3 and 4 bind to the p53-binding site of MDM2. The results here presented will be valuable for the structure-based design of novel and potent p53–MDM2 inhibitors.This research was partially supported by the Strategic Funding UID/Multi/04423/2013 , ERDF , COMPETE , and FCT under the projects PTDC/MAR-BIO/4694/2014, and INNOVMAR – Innovation and Sustainability in the Management and Exploitation of Marine Resources, reference NORTE-01-0145-FEDER-000035 , Research Line NOVELMAR . This work also received financial support from the European Union (FEDER funds POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/QUI/50006/2013 and the FCT project PTDC/DTP-FTO/1981/2014, “PEst-C/SAU/LA0003/2013”, “NORTE-07-0162-FEDER-00018 – Contributos para o reforço da capacidade do IPATIMUP enquanto actor do sistema regional de inovação” and NORTE-07-0162-FEDER-000067 – Reforço e consolidação da capacidade infraestrutural do IPATIMUP para o sistema regional de inovação”, both supported by ON.2 – O Novo Norte, through FEDER funds under the QREN. IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT. The authors also thank FCT for the grants of R.T. Lima ( SFRH/BPD/68787/2010 ), J. Soares ( SFRH/BD/78971/2011 ), and S. Gomes ( SFRH/BD/96189/2013 ; Doctoral Programme BiotechHealth), L. Raimundo ( PD/BI/113926/2015 , Doctoral Programme BiotechHealth)

Surface intermediate species of the 4-isobutylacetophenone adsorption-reaction over fosfotungstic Wells-Dawson heteropoly acid

Surface adsorbed species of isobutylbenzene and 4-isobutylacetophenone on bulk fosfotungstic Wells-Dawson acid have been screened in the present investigation. The evolution of chemisorbed species towards products was followed through infrared spectroscopy of systems containing liquid reactants and the solid acid kept at various temperatures. Isobutylacetophenone adsorbs on Brønsted acid sites of the heteropoly acid and further reacts towards a condensation product similarly to the reaction of acetophenone over other acid materials such as, mordenite, niobic acid and sulfated zirconia. The condensation product possesses well defined infrared signals at 1654 cm-1 and 1597 cm-1 that resemble the carbonyl stretching vibration and the double bond of dypnone. Additional signals at 1221 cm-1 give more evidences of the formation of a chalcone type compound. A reaction mechanism of the Aldol condensation of 4-isobutylacetophenone through an enol reactive intermediate is proposed.Fil: Matkovic, Silvana Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; ArgentinaFil: Valle, Graciela Manuela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; ArgentinaFil: Briand, Laura Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; Argentin

Synthesis of substituted flavone derivatives as potent antimicrobial agents

The biological activity of flavone has been enhanced by introducing heteroaryl moiety in C-2 position of chromone derivatives. Thus, 2-(1H-Indol-3-yl)-4H-chromen-4-one derivatives (6a-e) and 2-(2-chloroquinolin-3-yl)-4H-chromen-4-one derivatives (7a-e) were synthesized from corresponding chalcone. They were structurally confirmed by analytical and spectral data and evaluated for their antimicrobial activities. The results showed that this skeletal framework exhibited marked potency as antimicrobial agents.KEY WORDS: Chalcone, Flavone, Chromone, Antibacterial activity, Antifungal activity Bull. Chem. Soc. Ethiop. 2011, 25(3), 419-425