Novel benzofurane-pyrazole derivatives with anti-inflammatory, cyclooxygenase inhibitory and cytotoxicity evaluation

Novel benzofurane-pyrazolone hybrids have been synthesized for evaluating their anti-inflammatory and cytotoxic properties. 4-(2-chloroacetyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one were reacted with α-hydroxy aldehyde or α-hydroxy ketone derivatives to obtain nine novel pyrazolone derivatives. Structures were successfully elucidated by 1H NMR, 13C NMR, IR and HRMS. Enzyme inhibitory activity was measured on cyclooxygenases (COXs) as considered to address anti-inflammatory activity. Compound 2 showed the highest activity on both COX-1 and COX-2 subtypes with 12.0 μM and 8.0 μM IC50, respectively. This activity was found close to indomethacin COX-2 inhibition measured as 7.4 μM IC50. Rest of the compounds (1, 3–9) showed 10.4–28.1 μM IC50 on COX-2 and 17.0–35.6 μM IC50 on COX-1 (Compound 1 has no activity on COX-1). Tested compounds (1–9) showed activity on NO production. Only compound was the 4, which showed a low inhibition on IL-6 levels. Cell viability was up to 60% at 100 μM for all compounds (1–9) on RAW 264.7 and NIH3T3 cell lines, thus compounds were reported to be noncytotoxic.

Recent advancement and novel application of organocatalyzed aldol condensation reactions: A comprehensive review

Background: Aldol reactions play an important role in the development of organic synthesis-owing to their critical importance for the forming of carbon-carbon bonds while concurrently one or two chiral centers come into being. In the modern scenario, the Aldol condensation reaction has arisen as perhaps the most significant reaction for the formation of novel medicinal agents exhibits promising pharmacological activities. Objective: The purpose of this study is to present newer synthetic approaches through Aldol condensation reaction for the synthesis of diverse scaffolds to explore the promising various types of biological activities. Methods: Aldol condensation concerns the nucleophilic addition reaction of a ketone enolate to an aldehyde to form aldol or β- hydroxy ketone. Occasionally, the aldol addition product losing water molecule yields an α, β-unsaturated ketone. Results: Results showed that amino acids and all lengths of peptides are utilized as chiral catalysts. As of now, the arrangement of catalysts that have been accounted for is intensely one-sided towards proline. This is to some degree because of its exceptional status among the normally happening amino acids as an auxiliary amine and to its restricted underlying adaptability. Conclusion: The present study thus provides useful insight concerning the promising coherent way for the synthesis of prolinamide analogue of proline, through a direct asymmetric aldol condensation reaction. Thus, the current study summarizes various Aldol condensation reactions for the synthesis of novel agents as well as their promising pharmacological importance.

ASYMMETRIC ORGANOCATALYSIS

Dear Reader, Two basic reactions that were taught to us in the organic chemistry courses were the aldol condensation reaction and the Diels-Alder reaction. In aldol condensation, discovered by the French chemist Charles Wurtz in 1872, an enolate ion reacts with a carbonyl compound in the presence of an acid/ base catalyst to form a β-hydroxy aldehyde or a β-hydroxy ketone, usually followed by dehydration to give a conjugated enone. If the enolate ion and the carbonyl group are present in the same molecule, then the aldol reaction is intramolecular. It is an extremely useful carbon-carbon bond-forming reaction. The Diels-Alder reaction, discovered in 1928 by the German chemist Otto Diels and his student Kurt Alder, is the reaction between a conjugated diene and an alkene, a so-called dienophile, to form an unsaturated six-membered ring. It is called a cycloaddition reaction, since the reaction involves the formation of a cyclic product via a cyclic transition state. Uncatalysed Diels– Alder reactions usually require extended reaction times at elevated pressures and temperatures with the formation of by-products, hence various catalysts are employed. The Diels-Alder reaction also has great industrial relevance and the discoverers were crowned with the 1950 Nobel Prize in Chemistry. The aldol condensation reaction and the Diels-Alder reaction typically require catalysts, basically Brønsted acids, Brønsted bases, Lewis acids or Lewis bases. This triggered the minds of Dr. David MacMillan and Dr. Benjamin List for different reasons at different locations in USA around not so different times, more than twenty years ago, culminating in their being jointly awarded the Nobel Prize in Chemistry for this year.

Nanocrystals perovskites photocatalyzed singlet oxygen generation for light-driven organic reactions

Lead halide perovskite nanocrystals were prepared and used as photocatalysts for the in situ 1O2 generation to perform hetero Diels–Alder, ene and oxidation reactions with suitable dienes and alkenes. The methodology has been reasonably standardized and made applicable to a variety of olefinic substrates. The scope of the method is finely illustrated by the results in all the tested reactions, which allowed to obtain desymmetrized hydroxy-ketone derivatives, unsaturated ketones and epoxides. Some limitations were also observed especially in the case of the alkene oxidations as well as poor chemoselectivity was somewhere observed. Graphic abstract 1O2 generated by lead halide perovskite nanocrystals as photocatalyst in organic reactions.

The 1,3-Dipolar Cycloaddition Reactions of Nitrile Oxides in Water Media

: The 1,3-dipolar cycloadditions (DCs) of nitrile oxides (NOs) have been used as a powerful tool in synthetic organic chemistry. The cycloadducts arising from cycloadditions (CAs) of NOs to alkenes and alkynes (2-isoxazolines and isoxazoles respectively) are valuable synthetic intermediates because, among others, their capacity to mask other functionalities including α, β-unsaturated ketones, β-hydroxy carbonyl compounds and 1,3-aminoalcohols. In particular, the β-hydroxy ketone functionality is an illustrative example, making the NOs alkenes CAs reactions a synthetically equivalent methodology of aldol reactions. The vast majority of these reactions are carried out in organic solvents. Nevertheless, the use of water as an alternative solvent has evident advantages on the “Green Chemistry” concept. The critical discussion on the use of water instead of “conventional” solvents in the 1,3-DCs reactions of NOs is the objective of the present review.

Design, synthesis and molecular modeling study of substituted indoline-2-ones and spiro[indole-heterocycles] with potential activity against Gram-positive bacteria

Longstanding and firsthand infectious diseases are challenging community health threats. A new series of isatin derivatives bearing β-hydroxy ketone, chalcone, or spiro-heterocycle moiety, was synthesized in a good yield. Chemical structures of the synthesized compounds were elucidated using spectroscopic techniques and elemental analysis. Antibacterial activities of the compounds were then evaluated in vitro and by in silico modeling. The compounds were more active against Gram-positive bacteria, Staphylococcus aureus (MIC = 0.026–0.226 mmol L−1) and Bacillus subtilis (MIC = 0.348–1.723 mmol L–1) than against Gram-negative bacteria (MIC = 0.817–7.393 mmol L–1). Only 3-hydroxy-3-(2-(2,5-dimethylthiophen-3-yl)-2-oxoethyl)indolin-2-one (1b) was found as active as imipenem against S. aureus (MIC = 0.026 mmol L–1). In silico docking of the compounds in the binding sites of a homology modeled structure of S. aureus histidine kinase-Walk allowed us to shed light on the binding mode of these novel inhibitors. The highest antibacterial activity of 1b is consistent with its highest docking score values against S. aureus histidine kinase.

Direct Synthesis of Aromatic Imine Schiff Bases from β-Phenol Hydroxy Ketone

: A facile methodology has been developed to build carbon nitrogen double bond from ketones promoted by the hydroxyl groups in β-phenol hydroxy ketone. It is noteworthy that the halogenated β-phenol hydroxy ketone can chemoselectively react with amine to afford halogenated phenol imine. It is suitable for certain natural products and also suitable for water-based heteroamines. The method is low toxicity, widely applicable. This strategy is usually used to obtain moderate to good yields of aromatic amine Schiff base.