Natural Product Rottlerin Derivatives Targeting Quorum Sensing

Rottlerin is a natural product consisting of chalcone and flavonoid scaffolds, both of which have previously shown quorum sensing (QS) inhibition in various bacteria. Therefore, the unique rottlerin scaffold highlights great potential in inhibiting the QS system of Pseudomonas aeruginosa. Rottlerin analogues were synthesised by modifications at its chalcone- and methylene-bridged acetophenone moieties. The synthesis of analogues was achieved using an established five-step synthetic strategy for chalcone derivatives and utilising the Mannich reaction at C6 of the chromene to construct morpholine analogues. Several pyranochromene chalcone derivatives were also generated using aldol conditions. All the synthetic rottlerin derivatives were screened for QS inhibition and growth inhibition against the related LasR QS system. The pyranochromene chalcone structures displayed high QS inhibitory activity with the most potent compounds, 8b and 8d, achieving QS inhibition of 49.4% and 40.6% and no effect on bacterial growth inhibition at 31 µM, respectively. Both compounds also displayed moderate biofilm inhibitory activity and reduced the production of pyocyanin.

SYNTHESIS AND FUNCTIONALIZATION OF SOME PARA-R-PHENYLIMIDAZO[2,1-B][1,3,4]- THIADIAZOLE DERIVATIVES

The article describes the synthesis of new modifications of derivatives of 6-phenyl-, 6-piodophenyl- and 6-p-bromophenylimidazo[2,1-b][1,3,4]-thiadiazoles - N -((6-(4-iodophenyl)-2-R-imidazo[2,1-b][1,3,4]-thiadiazol-5-yl)methyl)-alkyl/ heterylamine based on the Mannich reaction, bromination 2((ethylsulfonyl)methyl)-6-phenylimidazo[2,1-b][1,3,4]-thiadiazole and the structure of the resulting compounds was established on the basis of IR spectroscopy. It was shown that the presence of substituents at the 2-nd position of the thiadiazole fragment and substituents at the 5th and 6th positions of the imidazole fragment of this heterocycle cause the appearance of a nonequivalent absorption band in the imidazo-thiadiazole fragment.

Synthesis and Characterization of Some Mannich Base Analogues of Ciprofloxacin: Antibacterial, Antifungal, and Cytotoxic Activities

The present work contains synthesis of six Mannich base analogues of ciprofloxacin 2-7 those have been prepared by the Mannich reaction to investigate some therapeutic assessment. The structure of the analogues has been established by FT-IR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis techniques. The derivatives were screened for their antimicrobial activities by the disc diffusion method. The antimicrobial activity of the analogues compared with the parent was evaluated against three Gram-positive, eight Gram-negative bacterial strains, and three different fungal strains. The synthesized compounds showed diverse antimicrobial profiles among which derivatives 2, 3 & 6 possessed enhanced activity in contrast to the ciprofloxacin. Additionally, unlike ciprofloxacin, most of the derivatives were found to demonstrate antifungal activity against Candida albicans. Cytotoxicity was also made against brine shrimp lethality assay. Interestingly, most of the derivatives revealed enhanced cytotoxic activity than that of ciprofloxacin.

Synthesis n-oxides of pyridylacethylene amines based on 2-methyl-5-ethynylpyridine

The aim of this work is to study the reaction of 2-methyl-5-ethynylpyridine N-oxide with some aliphatic and aromatic amines to obtain N-oxides of pyridylacetylenic amines. 2-Methyl-5-ethylpyridine converted to 2-methyl-5-vinylpyridine by dehydrogenation, and 2-methyl-5-ethynylpyridine obtained by bromination and dehydrobromination. 2-methyl-5-ethynylpyridine N-oxide synthesized by oxidation of 2-methyl-5-ethynylpyridine with perhydrol in acetic anhydride. The synthesis of N-oxides of pyridylacetylenic amines by the Mannich reaction carried out. The effect of the solvents: methanol, ethanol and n-dioxane, the catalyst, and the reaction time on the yield of the final product studied. The structure and composition of the synthesized PAA N-oxides were established using IR and PMR spectroscopy.

Three-component radical homo Mannich reaction

Aliphatic amine, especially tertiary aliphatic amine, is one of the most popular functionalities found in pharmaceutical agents. The Mannich reaction is a classical and widely used transformation for the synthesis of β-amino-carbonyl products. Due to an ionic nature of the mechanism, the Mannich reaction can only use non-enolizable aldehydes as substrates, which significantly limits the further applications of this powerful approach. Here we show, by employing a radical process, we are able to utilize enolizable aldehydes as substrates and develop the three-component radical homo Mannich reaction for the streamlined synthesis of γ-amino-carbonyl compounds. The electrophilic radicals are generated from thiols via the desulfurization process facilitated by visible-light, and then add to the electron-rich double bonds of the in-situ formed enamines to provide the products in a single step. The broad scope, mild conditions, high functional group tolerance, and modularity of this metal-free approach for the synthesis of complex tertiary amine scaffolds will likely be of great utility to chemists in both academia and industry.

Improved understanding of technical lignin functionalization through comprehensive structural characterization of fractionated pine kraft lignins modified by the Mannich reaction

Amino alkylation of technical lignins via the Mannich reaction can be used as an analytical derivatization technique, but also in an applied manner to improve kraft lignin hydrophilicity or metal...

Novel Mannich Base Derivatives: Synthesis, Characterization, Antimicrobial and Antioxidant Activities

: In this study, 3-alkyl(aryl)-4-(4-ethylbenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones 2 were synthesized as explained in the literature. Then, the Schiff bases 2 were treated with morpholine/ N-methylpiperazine/ 3-methylpiperidine/ 4-piperidinecarboxamide in the presence of formaldehyde according to the Mannich reaction to synthesize novel Mannich bases 3, 4, 5, and 6 types, respectively. The structural analyses of twenty four compound which synthesized new, were characterized using proton/ carbon 13 nuclear magnetic resonance (1H/ 13C-NMR), Infrared (IR) spectoscopic techniques. In addition, the antimicrobial activity of the compounds was determined on six bacteria by using the agar well diffusion method.The most effective results against gram positive and negative bacteria were observed in 6(a-d) and 6f compounds. Also, the antioxidant capacities of the substances were investigated by three different methods (DPPH, reducing power, metal chelation). All compounds 3-6(a-f) showed metal chelating effect.

Modified and unmodified technical lignins as flame retardants for polypropylene

Polyolefins used in building materials and furniture require the use of flame-retardant (FR) additives to improve their fire safety. Such additives should be safe to humans and the environment, and preferably bio-based. In the present work, the FR performance of unmodified and chemically modified technical lignins was compared to that of the ammonium polyphosphate/pentaerythritol (APP/PER) intumescent system in a polypropylene (PP) matrix. Micro-scale combustion calorimetry (MCC) was used to study the peak heat release rate (PHR), temperature at PHR (TPHR), total heat release (THR) and char yield upon thermal decomposition of milligram-scale specimens. The PP/lignin composites showed up to 41% lower PHR and up to 36% lower THR compared to pure PP as well as large char residues. Based on the same parameters, especially the PP/lignin composites made with modified lignins outperformed the reference PP/APP/PER system and the PP/APP/lignin composites where unmodified lignin was used with APP. The most promising PP/lignin composites were prepared with partially demethylated/demethoxylated and depolymerised kraft lignin (‘CatLignin’), modified by the Mannich reaction to a nitrogen content of 13.5%.