Synthesis and antibacterial activity of four natural chalcones and their derivatives

Four natural chalcones bearing hydroxyisoprenyl or prenyl groups, named Paratocarpin E (2), Xanthoangelol D (3), Angusticornin A (4) and Kanzonol C (5), were prepared by employing the Claisen-Schmidt condensation as the key step. In an attempt to investigate the effect of the hydroxyisoprenyl group on biological activity, two of their derivatives were also prepared for antibacterial activity research. The synthesized compounds were investigated for their expected antibacterial activities against Gram positive bacteria (Bacillus subtilis, Staphylococcus aureus) as well as Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa). Paratocarpin E (2) was found to be the most potent against two Gram positive bacteria while the majority of the remaining compounds showed promising activity as well. However, all of the compounds were inactive against both Gram-negative bacteria.     

Synthesis of various fused heterocyclic rings from thiazolopyridine and their pharmacological and antimicrobial evaluations

Various fused-heterocyclic-derivatives containing thiazolopyridine moieties has been synthesized by allowing 5-aminothiazolo[3,2-a]pyridine derivative 1 to undergo annulations reactions with different reagents under different-reaction conditions. The biological assessment of compounds 2 , 11 , 14 , 15 , and 19 showed remarkable antimicrobial activities. In addition, selected derivatives of the products were screened for their anticancer activities against two tumor cell lines using MTT assay and the results showed that some of these compounds have potent cytotoxic effect, as concluded from their IC₅₀ values. Meanwhile, compounds 3a , 7 have exhibited very strong potency as anticancer candidates. Thiazolopyridine structures have been confirmed as a useful lead compounds for the development of new anticancer agents. Molecular docking showed that,-some of the synthesized compounds more suitable inhibitor against-ALR2 with farther alteration in future.     

Synthesis of isomeric benzodipyrrolenines and their derivatives

The Fischer reaction was used to synthesize 2,3,3,5,5,6-hexamethyl-3H,5H-benzo[1,2-b5,4-b]dipyrrole and 2,3,3,7,8,8-hexamethyl-3H,8H-benzo[1,2-b3,4-b]dipyrrole from the dihydrazone obtained by the action of methyl isopropyl ketone on m-phenylenedihydrazine. Centrosymmetrical 2,3,3,6,7,7-hexamethyl-3H,7H-benzo[1,2-b4,5-b]dipyrrole was synthesized from p-phenylenediamine and methyl bromoisopropyl ketone. Mono- and diquaternary salts were obtained from the new bases. The diquaternary salts were converted to bismethylene bases.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 614–617, May, 1971.     

Synthesis and characterization of some chalcones and their cyclohexenone derivatives

A series of chalcones and their derivatives have been synthesized. Chalcones, 1-(1,3-benzodioxol-5-yl)-3-(aryl)-prop-2-en-1-ones were prepared by the aldol condensation of 1-(1,3-benzodioxol-5-yl)ethanones and aryl aldehydes. Based-catalyzed condensation of 1-(1,3-benzodioxol-5-yl)-3-(aryl)prop-2-en-1-ones with ethyl acetoacetate yields corresponding ethyl 4-(1,3-benzodioxol-5-yl)-6-(aryl)-2-oxocyclohex-3-ene-1-carboxylates. Some of the synthesized chalcones were reported in the literature; the newly synthesized compounds were characterized by single crystal X-ray studies, IR, ¹H-NMR and LCMS mass spectral analysis.     

Synthesis and antioxidant activity of new hydroxy derivatives of chalcones

New hydroxy derivatives of chalcones obtained via a condensation of 3-acetyl-2H-chromen-2-one with 2,4-dihydroxy- and 4-hydroxy-benzaldehydes and via an aldol crotonic condensation of methyl N-(4-acetylphenyl)carbamate with 4-hydroxy-3,5-di(tert-butyl)benzaldehyde have been isolated and characterized. A wide range of promising biological activity of the synthesized compounds, including the radical scavenging and antioxidant ones, was predicted by the in silico method. The anti- and pro-oxidant activities in model systems of peroxidation of cis-9-octadecenoic (oleic) acid and lipids from the liver homogenate of tilapia were estimated in vitro. The presence of sterically hindered hydroxy groups and a chromene moiety provides the prolonged antioxidant activity of new hydroxy derivatives of chalcones.

     

Synthesis,dimerization, and biological activity of hexaoxygenated chalcones related to calythropsin and combretastatins

Five new hexaoxygenated chalcones and one new chalcone photodimer were synthesized and their cytotoxicity against leukemia cell line L-1210 was studied. The three more active compounds were tested for their activity on the inhibition and promotion of tubulin assembly and it was found that these chalcones do not interfere with the tubulin-microtubule system at cytotoxic concentrations, and therefore operate by some different mechanism of action.     

Synthesis of 5-methylsulfonylpyrimidines and their fused derivatives

The interaction of available 2-methylsulfonyl-3-ethoxyacrylonitrile with amidine, their analogs, and aminoazoles containing amidine fragment, yielding earlier unknown 4-amino-5-methylsulfonylpyrimidines and their fused derivatives has been studied.     

Synthesis and antitumor activity of fused quinoline derivatives

Some tetracyclic quinolines (9 and 14) with a [2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino side chain were prepared and their deoxyribonucleic acid (DNA) intercalative properties, KB cytotoxicity, antitumor activity (P388 leukemia), and ability to induce topoisomerase II dependent DNA cleavage were investigated. The indoloquinoline derivative 9 exhibited the most potent activity (dose = 6.3 mg, T/C% = 300) in this series. The steric structural features of the chromophores of the compounds previously and newly synthesized were studied by a computer-associated molecular graphics technique. Relationships between the steric structural features of the chromophores and biological activities are also discussed.     

Synthesis of fluorescent polyisoprene nanoparticles and their uptake into various cells

Fluorescent polyisoprene nanoparticles were synthesized by the miniemulsion technique as marker particles for cells. The uptake of the non-functionalized polyisoprene nanoparticles, without any transfection agents, into different adherent (HeLa) and also suspension (Jurkat) cell lines is strikingly efficient and fast compared to other polymeric particles, and leads to high loading of the cells. The intracellular polyisoprene particles are localized as single particles in endosomes distributed throughout the entire cytoplasm. The uptake kinetics shows that particle internalization starts during the first minutes of incubation and is finished after 48 h of incubation. Since (unfunctionalized) polystyrene particles show a comparable, low uptake behavior in cells, the uptake rates can be tuned by the amount of polystyrene in polyisoprene/polystyrene copolymer particles. As polyisoprene nanoparticles are internalized by different cell lines that are relevant for biomedical applications, they can be used to label these cells efficiently if a marker is incorporated in the particles. As polyisoprene is not or is hardly biodegradable the particles should be suited for long-term applications.     

Synthesis of various arylated trifluoromethyl substituted indanes and indenes,and study of their biological activity

A series of 1-trifluoromethyl substituted indanes and indenes bearing aryl groups in positions 1 and/or 3 of the indane core have been synthesized mainly by electrophilic cyclization and arylation of the corresponding trifluoromethylated allyl and propargyl alcohols. The distinctly lipophilic compounds thus obtained were tested against various components of human endocannabinoid system. None of the compounds displayed affinity toward CB₁ or CB₂ receptors. Two compounds inhibited monoacylglycerol lipase (MAGL) and three compounds showed inhibition of anandamide (AEA) uptake. The latter can be related to the low-micromolar inhibition of fatty acid amide hydrolase (FAAH) inhibition displayed by one of these compounds.     

Synthesis of some fused heterocyclic systems and their nucleoside candidates

A series of pyridofuro compounds were synthesized from 4-(4-chlorophenyl)-1,2-dihydro-2-oxo-6-(thiophen-2-yl)pyridine-3-carbonitrile (1) as starting material. Alkylation of 1 with ethyl bromoacetate gave the corresponding ester 2, which was condensed with hydrazine hydrate to afford the corresponding acid hydrazide derivative 3. Thrope-Ziegler cyclization of 2 with sodium methoxide gave furo[2,3-b]pyridine derivative 4, which was reacted with thiosemicarbazide, allyl isothiocyanate, formamide or hydrazine hydrate to give furopyridine derivatives 5–8, respectively. The latter compound 8 was cyclized with acetylacetone or formic acid to give the corresponding compounds 9 and 10, respectively. Furthermore, sulfurization of 1 with P₂S₅ gave the corresponding thioxopyridine 11, which was reacted with glycosyl (or galactosyl) bromide, morpholine or piperidine to give the corresponding thioglycoside 12a,b and Mannich base 14a,b derivatives. The deacetylation of 12a,b gave the corresponding deacetylated thioglycosides 13a,b, respectively. All the newly synthesized compounds were characterized by the elemental analyses and spectroscopic evidences (IR, ¹H- and ¹³C NMR).     

Synthesis, cytotoxicities and DNA-binding affinities of benzofuran-3-ols and their fused analogs

A series of benzofuropyrazoles 2a-i were synthesized in 10-92% from the reaction of 2-aroylbenzofuran-3-ols 1a-i with hydrazine hydrate, and screened for their antitumor activities toward four human solid tumor cell lines, including gastric carcinoma cells MKN45, hepatocellular carcinoma cells HepG2, breast cancer cells MCF-7, and lung cancer cells A549. The results indicated that both compounds 1a-i and 2a-i displayed moderate antitumor activities. Among them, compound 2e exhibited potent inhibitory activity toward all the four tumor cell lines. In addition, compounds 1e and 2e showed strong DNA-binding affinities, and induced an increase in the viscosity of calf-thymus DNA, suggesting that they might act as an intercalator.