Lucian Gabriel Bahrin

Antibacterial activity and proposed action mechanism of a new class of synthetic tricyclic flavonoids.

This study reports on the inhibitory and bactericidal properties of a new synthetized flavonoid.

The antibacterial properties of sulfur containing flavonoids.

Some dithiocarbamic esters bearing a flavanone backbone, as well as their corresponding 1,3-dithiolium salts were tested against Staphylococcus aureus and Escherichia coli. The 1,3-dithiolium tricyclic flavonoids display good inhibitory properties against both Gram-positive and Gram-negative pathogens.

Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

Summary A structure–activity relationship study concerning the antibacterial properties of several halogen-substituted tricyclic sulfur-containing flavonoids has been performed. The compounds have been synthesized by cyclocondensation of the corresponding 3-dithiocarbamic flavanones under acidic conditions. The influence of different halogen substituents on the antibacterial properties has been tested against Staphylococcus aureus and Escherichia coli. Amongst the N,N-dialkylamino-substituted flavonoids, those having an N,N-diethylamino moiety exhibited good to excellent antimicrobial properties against both pathogens. Fluorine-substituted flavonoids were found to be less active than those bearing other halogen atoms.

[2.2]Paracyclophane derivatives containing tetrathiafulvalene moieties

Summary The synthesis of [2.2]paracyclophane derivatives containing tetrathiafulvalene units has been accomplished by the coupling reaction of 4-([2.2]paracyclophan-4-yl)-1,3-dithiol-2-thione in the presence of trimethylphosphite. The 1,3-dithiol-2-thione derivative was in turn synthesized by the regioselective bromination of 4-acetyl[2.2]paracyclophane, then through the corresponding dithiocarbamates and 1,3-dithiolium salts.

A novel synthetic flavonoid with potent antibacterial properties: In vitro activity and proposed mode of action

The emergence of pathogenic multidrug-resistant bacteria demands new approaches in finding effective antibacterial agents. Synthetic flavonoids could be a reliable solution due to their important antimicrobial activity. We report here the potent in vitro antibacterial activity of ClCl-flav—a novel synthetic tricyclic flavonoid. The antimicrobial effects were tested using the minimum inhibitory concentration (MIC), time kill and biofilm formation assays. Fluorescence microscopy and scanning electron microscopy were employed to study the mechanism of action. MTT test was used to assess the cytotoxicity of ClCl-flav. Our results showed that Gram positive bacteria were more sensitive (MIC = 0.24 μg/mL) to ClCl-flav compared to the Gram negative ones (MIC = 3.9 μg/mL). We found that our compound showed significantly enhanced antibacterial activities, 32 to 72-fold more active than other synthetic flavonoids. ClCl-flav showed bactericidal activity at concentrations ranging from 0.48 to 15.62 μg/mL. At twice the MIC, all Escherichia coli and Klebsiella pneumoniae cells were killed within 1 h. Also ClCl-flav presented good anti-biofilm activity. The mechanism of action is related to the impairment of the cell membrane integrity. No or very low cytotoxicity was evidenced at effective concentrations against Vero cells. Based on the strong antibacterial activity and cytotoxicity assessment, ClCl-flav has a good potential for the design of new antimicrobial agents.

Intramolecular interactions in [2.2]paracyclophanes

C organic sulfoxides are important synthons and chiral auxiliaries in synthetic organic chemistry. Therefore synthesis of chiral sulfoxide is an active area of continuing research interest. The most common method for the preparation of sulfoxide is by the oxidation of their corresponding sulfides. Both the chemical and biological catalysts have been developed for this purpose. Though the reaction conditions for the preparation of chiral organic sulfoxides. With hope that some of them will produce the desired sulfoxidation in a good enantiomeric excess. Being involving in biological catalysts are milder and ecofriendly in comparison to those involving in chemical catalysts, they are of limited practical use. This communication reports a crude preparation of ascorbate peroxidase from Musa paradisiaca which can be conveniently prepared and used for the transformation of methyl phenyl sulfide to its sulfoxide. This is the report of sulfoxide formation using a plant enzyme. The method for the preparation of enzyme from Musa paradisiaca has been developed. The enzymatic characteristics like Km for the substrates sulfide and H2O2, pH and temperature optima of the enzyme have been determined. The enzymatic transformation of sulfide to its sulfoxide has been demonstrated. The results of the above studies will be presented in the conference.M reactions (MCRs) are important processes from atom and step economy point of view. 1,3-Dipolar cycloadditions (1,3-DC) involving azomethine ylides and electrophilic alkenes are good examples for this type of transformation but are not so frequently described. In this lecture, the thermal and silver mediated multicomponent 1,3DC between α-amino esters, dipolarophiles and aldehydes will be considered. This 1,3-DC allows the synthesis of highly substituted pyrrolidines under conventional or MW heating. In general, 4,5-endo diastereoselectivity was mainly observed and 2,5-cis-cycloadducts are formed according to a W-shaped dipole. When this MCR was performed with 2-oxoaldehydes, the 1,3-DC takes place under silver acetate catalysis at rt [3b]. On the other hand, the multicomponent 1,3-dipolar cycloaddition between different proline esters, aldehydes and dipolarophiles afford highly substituted pyrrolizidines will also be described. The corresponding highly substituted pyrrolizidines are obtained in all cases with 2,5-trans-relative configuration between two electron-withdrawing groups and major endo-selectivity with 2,4-cis-relative configuration. The use of (2S,4R)-4hydroxyproline methyl ester hydrochloride allowed the synthesis of enantiomerically enriched pyrrolizidines. When pipecolic acid alkyl esters are used the corresponding indolizidines can be prepared under thermal reaction conditions.Background: The hypervalent iodine (III) compounds, (diacetoxyiodo)benzene (DIB) possess numerous applications as oxidizing reagent. A particularly useful methodology for the oxidative α-functionalization of enolizable carbonyl compounds involves DIB in methanolic potassium hydroxide resulting in the synthesis of α-hydroxydimethylacetals. The reaction is also applicable to enones which cannot form anion by α-hydrogen abstraction such as chromone, chalcone, flavones and flavanone.H compounds are the most valuable sources of diverse biologically active molecules. The utility of heterocyclic structures is the ability to synthesize one library based on one core scaffold and to screen it against a variety of different receptors, yielding several active compounds. Of these, particularly the indolic scaffolds are the important substances of a large number of important compounds that occur in nature. Therefore, the invention of new synthetic routes to functionalize the indolic scaffolds continues to command wide interest due to the numerous natural products and biologically significant compounds whose structures incorporate these heterocyclic systems. In contrast, few existing methods provide efficient and regiocontrolled access to functionalize the indolic molecules. In this context, the transition metal-catalyzed C-H bond activation strategy provides a powerful vehicle for the direct assembly and functionalization of the bioactive heterocyclic molecules. This approach is highly modular and is especially well-suited for the preparation of carbon-carbon and carbonheteroatom bond due to the minimization of stoichiometric metallic waste and of the costs associated with substrate preactivation. These considerations led us to investigate the possibility of functionalization of indolic scaffolds at the C7–position which is highly challenging in C-H activation events. Moreover, the constructed C7–functionalized indolic compounds were tested for in vitro cytotoxicity against various human cancer cell lines and some of them were found to display most potent anticancer activity, compared to that of anticancer doxorubicin a positive control.Since its discovery in 1949 by Brown and Farthing [1], [2.2]para-cyclophane has been intensely studied by chemists. Consisting of two benzene rings bound together by two ethano bridges, the [2.2]paracyclophane core can undergo chemical transformations specific to both aliphatic and aromatic compounds, resulting in a wide variety of functionalized [2.2]paracyclophanes. Thus, cyclophanes are ideal model systems to investigate whether and how functionalized groups can interact and react with each other. Because of the rigid molecular framework provided by the paracyclophane moiety and its short interannular distance, functional groups in pseudo-geminally substituted [2.2]paracyclophanes are often held in such a position as to allow highly specific reactions to take place between them. Both the parent hydrocarbon and its derivatives have been used in asymmetric catalysis, optoelectronics and polymer synthesis.T development of protocols for the construction of C-C bond following the principles of green chemistry is one of the most challenging tasks in organic synthesis. Since more and more organic solvents are blacklisted due to their damaging effect on human health and environment, organic reactions under solvent-free reaction conditions (SFRC), mainly fulfill these principles. C-C bond forming reactions display one of the most important implements for the synthesis of complex organic products, many of them developed bioactivity as drugs or agrochemicals. C-C bond formation by direct coupling of alcohols with other partners could be a very attractive strategy from practical, atom-efficient and environmental point of view, producing water as only a by-product of the reaction. Because of their lower leaving group ability, hydroxyl moieties are rarely substituted under mild conditions and must often be activated before treatment with nucleophiles. Numerous related methodologies have been elaborated using a substoichiometric amount of Brønsted acids, metals ions, Lewis/Brønsted acid combination or other promoters which have been touched on by several excellent reviews and recent advanced related reports. Silver hexafluoroantimonate (V) (AgSbF6) has been used as a catalyst for direct α-alkylation of unactivated ketones using benzylic alcohols. While a new method for direct benzylation/allylation of malonates with alcohols via a palladium catalyzed Tsuji-Trost type reaction was developed. Accordingly, the development of an efficient and environmentally benign catalytic methodology for C-C bond formation remains an attractive research subject. We report new, efficient and selective methodology for the direct C-C bond formation through the direct coupling of various benzyl alcohols with a different type of electron rich compounds including 1,3-dicarbonyl compounds, heteroatom benzo-cyclenes, phenyl substituted alkenes, or tertiary benzyl alcohols, bearing a vicinal hydrogen atom as alkene precursors, catalyzed by N-halo organic compound as a metaland acid-free catalyst under SFRC, enhancing the green chemical profiles of these transformations.Z have the chemical formula Mx/n[(AlO2)x(SiO2)y].wH2O, where the charge-balancing nonframework cation M has valence n, x is 2.0 or more, and y is the moles of water in the voids. The Al and Si tetrahedral atoms, or T-atoms, form a threedimensional (3D) framework of AlO4 and SiO4 tetrahedra linked together by shared oxygen ions. Although SiO4 tetrahedra are charge balanced, AlO4 tetrahedra has a negative charge balanced by a positive charge on M while water molecules lie within the pores of zeolites. The water can be expelled upon by heating and evacuation and may be replaced by a number of small inorganic and organic guests. We are developing novel nanoporous zeolite materials for the treatment of waste including radioactive, toxic gas/chemicals separation, pesticide/herbicide management, sewage treatment etc. Zeolite acts as auxiliary as well as functional support in gas sensing. Zeolites has been modified dually i.e. both surface modified and ion exchanged present inside in the pore cavity. Also several polymer based composites has been synthesized for gas sensing purposes. This modification in zeolite structure increases its sorption capacity, sensitivity and recyclability. The parent sodium form was also modified to proton form to increase their catalytic activity and further applying for organic drug synthesis.T vascular endothelial growth factor receptor-2 (VEGFR-2) is considered as the most important transducer of VEGFdependent angiogenesis. VEGFR-2 is highly up-regulated in several solid tumors and plays a critical role in the process of tumor angiogenesis; therefore, VEGFR-2 inhibition emerged as a prime approach for discovering new therapies for many human angiogenesis-dependent malignancies. A novel series of indole derivatives was synthesized and tested for their cytotoxic activities against a panel of 60 cancer cell lines. A molecular docking study was also carried out to determine their binding modes and binding affinities in the VEGFR-2 active site using a reference VEGFR-2 inhibitor, sorafenib (Figure 1). The synthesized compounds exhibited a broad spectrum antiproliferative activity on 60 cell lines with growth inhibition percent (GI)% ranging from 31 to 82.5%. An indoloimidazolone derivative was found the most potent VEGFR-2 inhibitor with IC50 of 0.07 μM more potent than that of sorafenib (0.09 μM). The molecular docking study attributed the promising inhibitory activity on VEGFR-2 of this series to their hydrophobic interaction with the VEGFR-2 binding site hydrophobic side chains and their hydrogen bonding interaction with the key amino acids Glu885 and Asp1046.

Flavonoids – Small Molecules, High Hopes

Abstract This brief review takes a look at flavonoids, a wide class of polyphenols, which are regarded as plant secondary metabolites. Their roles in plants are diverse and little understood. They can act as growth hormone modulators, phytoalexins, they offer UV protection, contribute to pollen viability and can function as signaling molecules in establishing symbiotic relationships. Flavonoids were also found to have a range of beneficial effects for the human body. Their anticancer, antioxidant, anti-inflammatory and cardioprotective activity, as well as their antibacterial, antiviral and antihelmintic properties make them promising candidates for the design of new drugs.

4-Bromo-2-[5-methyl-2-(morpholin-4-yl)-1,3-thia­zol-4-yl]phenol

In the title compound, C14H15BrN2O2S, synthesized by the reaction of the corresponding phenacyl thiocyanate with morpholine, the dihedral angle between the 1,3-thiazole ring and the phenolic substituent ring is 23.46 (10)° as a result of the steric influence of the ortho-methyl group on the thiazole ring. A strong intramolecular phenolic O—H⋯N hydrogen bond is present in the molecule. In the crystal, a weak C—H⋯Ophenol hydrogen bond gives rise to chains lying parallel to [20-1]. A short intermolecular Br⋯Omorpholine interaction is also present [3.1338 (19) Å].

3-Methylpiperidinyl Carbodithioates as Building Blocks for 1,3-Dithiolium Derivatives

Abstract New 1,3-dithiolium derivatives have been synthesized by heterocyclocondensation of various 3-methylpiperidinyl carbodithioates derived from 2-hydroxypropiophenones. Thus, 1,3-dithiolium perchlorates have been obtained by the treatment of the corresponding dithiocarbamates with a mixture of acetic and sulfuric acid, followed by the addition of perchloric acid. 1,3-Dithiolium perchlorates have been converted to the corresponding 2-(1,3-dithiolium) phenolates under weak basic conditions. These phenolates exhibit mesoionic character with an internal charge transfer absorption band.