Solvent-free synthesis and antibacterial studies of some quinolinones

Abstract  

Solvent-free, microwave-induced condensation of 2-aminoaryl alkyl ketones and ethyl 3-oxobutanoate in the presence of amberlite Na sr1L gave quinolinones in high yield when compared to other catalysts. Further, N-alkylation of the quinolinones was carried out effectively with various halides using amberlite Na sr1L. An N-alkylated quinolinone exhibited enhanced activities against B. subtilis, E. coli, and P. aeruginosa, similar to standard drug ampicillin. Two compounds showed effective activity against S. aureus, and one resulted in moderate activity against E. coli.     

Synthesis of 5-spirocyclohexyl-2,4-dithiohydantoin derivatives: a potential anti-leishmaniasis agent

Abstract  

A series of spiro-dithiohydantoins were synthesized by heating a mixture of 5-spirocyclohexyl-2,4-dithiohydantoin potassium salt and 3-chloropropanoyl chloride. These compounds were synthesized and evaluated for their activity against five Leishmanial strains in the promastigote stage in vitro. Seventy-two hours inoculation of a variety of products gave an IC ₁₀₀ and average IC ₅₀ values of 1.25 and 0.376 mg/cm³ against all Leishmanial strains tested.     

Synthesis and antiproliferative activity of multisubstituted N-fused heterocycles against the Hep-G2 cancer cell line

Abstract  

Pyrrolo[1,2-a]imidazole and pyrrolo[2,1-b]thiazole derivatives were synthesized in a one-pot procedure by [3 + 2] cycloaddition reactions of the corresponding imidazolium ylides and thiazolium ylides with an alkene followed by oxidative aromatization of the primary cycloadducts under the action of the mild oxidant tetrakispyridinecobalt(II) dichromate. Antiproliferative activity of 14 new bicyclic N-fused heterocycles against the human hepatocellular liver carcinoma (Hep-G2) cell line were examined by the MTT method. Some of the compounds showed favorable antiproliferative activity, especially compound 3i displayed potent antiproliferative activities with an IC₅₀ value of 0.36 μg/cm³.     

Myosin-cross-reactive antigen (MCRA) protein from <Emphasis Type="Italic">Bifidobacterium breve</Emphasis> is a FAD-dependent fatty acid hydratase which has a function in stress protection

Background  

The aim of this study was to determine the catalytic activity and physiological role of myosin-cross-reactive antigen (MCRA) from Bifidobacterium breve NCIMB 702258. MCRA from B. breve NCIMB 702258 was cloned, sequenced and expressed in heterologous hosts (Lactococcus and Corynebacterium) and the recombinant proteins assessed for enzymatic activity against fatty acid substrates.     

Derivatives of 5-nitro-1H-benzo[de]isoquinoline-1,3(2H)-dione: design, synthesis, and biological activity

Abstract  

A series of mono and bis-2-(2-(dimethylamino)-ethyl)-5-nitro-1H-benzo[de]isoquinoline-1,3(2H)-diones with different amino side chains, a novel family of antitumor agents, has been designed and synthesized. Their antitumor activity was evaluated against HeLa, A549, P388, HL-60, MCF-7, HCT-8, and A375 cancer cell lines in vitro. Preliminary results showed that most of the derivatives had antitumor activity comparable with that of mitonafide, with IC ₅₀ values of 10⁻⁶–10⁻⁵ M. More importantly, the derivatives had distinct antitumor selectivity against different cancer cell lines. This work provided a novel class of mitonafide-based lead compounds with improved antitumor selectivity against cancer cell lines for further optimization.     

Synthesis and anticancer activity of some 1,5-diaryl-3-(3,4,5-trihydroxyphenyl)-1H-pyrazolo[4,3-e][1,2,4]triazines

Abstract  

The deregulation of cell cycle components in cancer cells has provided a rationale for the development of small molecule inhibitors of cyclin-dependent kinases as novel anticancer drugs. A series of 1,5-diaryl-3-(3,4,5-trihydroxyphenyl)-1H-pyrazolo[4,3-e][1,2,4]triazines was synthesized and their kinase inhibitory activity and cytotoxicity against several cancer cell lines has been evaluated. Some of the compounds of the series exhibited induction of caspase-dependent cell death and inhibition of cyclin-dependent kinase 2 (CDK2).     

One-pot synthesis of diphenyl pyrazolylmethylanilines via reductive amination using NaBH<Subscript>4</Subscript>/I<Subscript>2</Subscript> and their antimicrobial screening

Abstract  

Direct reductive amination of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde and 3-(4-methylphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde with various substituted aromatic amines using NaBH₄ in the presence of I₂ as reducing agent is described. The reaction has been carried out in anhydrous methanol under neutral conditions at room temperature. The structure of newly synthesized diphenyl pyrazolylmethylanilines was established on the basis of IR, ¹H, ¹³C NMR, and mass spectral data. All diphenyl pyrazolylmethylaniline derivatives were tested in vitro for their antifungal and antibacterial activity against different strains of fungi and bacteria. Most of the compound exhibited considerable antifungal activity but poor antibacterial activity against the test strains.     

Studies on the synthesis, characterization, binding with DNA and activities of two cis-planaramineplatinum(II) complexes of the form: cis-PtL(NH3)Cl2 where L = 3-hydroxypyridine and 2,3-diaminopyridine

Background  

Cis-planaramineplatinum(II) complexes like their trans isomers are often found to be active against cancer cell lines. The present study deals with the synthesis, characterization and determination of activity of new cis-planaramineplatinum(II) complexes.     

Synthesis, characterization, and antifungal activity of biaryl-based bis(1,2,3-triazoles) using click chemistry

Abstract  

Click chemistry was used to synthesize a series of biaryl-based bis(1,2,3-triazoles). Their antifungal activity was evaluated against three soil-borne plant pathogenic fungi, viz. Rhizoctonia bataticola, Sclerotium rolfsii, and Fusarium oxysporum, using the food poison technique at concentrations of 62.5–500 μg/cm³.     

Synthesis, chemical properties, and antimicrobial activity of 2- and 2,3-substituted [(tetrahydro-2,4-dioxopyrimidin-1(2H)-yl)phenoxy]naphthalene-1,4-diones

Abstract  

Mono- and disubstituted [(tetrahydro-2,4-dioxopyrimidin-1(2H)-yl)phenoxy]naphthalene-1,4-diones were synthesized by the reaction of dihydro-1-(3-hydroxy- and 4-hydroxyphenyl)pyrimidine-2,4(1H,3H)-diones and their 5- and 6-methyl derivatives with 2,3-dichloro-1,4-naphthoquinone. Their stability in alkaline and acidic media was investigated. Four of the compounds exhibited good antimicrobial activity against Staphylococcus aureus, Mycobacterium luteum, Candida tenuis, and Aspergillus niger.     

Toward the synthesis and biological evaluation of hirsutide

Abstract  

The present investigation deals with the synthesis of a N-methylated cyclotetrapeptide, hirsutide (2), by coupling of the dipeptide units Boc-l-phenylalanyl-l-N-methylphenylalanine-OH and l-valyl-l-N-methylphenylalanine-OMe followed by cyclization of the linear tetrapeptide fragment. The chemical structure was established on the basis of analytical as well as spectroscopic data. The newly synthesized cyclic peptide was subjected to pharmacological screening and found to be highly potent against the gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae at 6 μg cm⁻³. In addition, potent antihelmintic activity against the earthworms Megascoplex konkanensis and Pontoscotex corethruses at 1 and 2 mg cm⁻³, and potent cytotoxic activity against Dalton’s lymphoma ascites and Ehrlich’s ascites carcinoma cell lines with IC₅₀ values of 14 and 22 μM were also observed. Studies revealed that the pentafluorophenyl ester method employing a catalytic amount of N-methylmorpholine proved to be better for cyclization of the linear tetrapeptide unit.     

Design, synthesis, and bioactivity of cyanonitrovinyl neonicotinoids as potential insecticides

Abstract  

A series of cyanonitrovinyl neonicotinoids were designed and synthesized via five steps in about 35% overall yields. All compounds were structurally characterized by ¹H nuclear magnetic resonance (NMR), ¹³C NMR, infrared (IR), and high-resolution mass spectrometry (HRMS), and single-crystal X-ray diffraction analysis of 2-[1-[(6-chloropyridin-3-yl)methyl]-2-imidazolidinylidene]-2-nitroacetonitrile revealed that the double bond is (E)-configured. The preliminary agriculture bioassay indicated that one compound exhibited moderate insecticidal activity against pea aphid.     

Synthesis and biological activity of novel 4- and 6-(1-alkyl/aryl-1H-benzimidazol-2-yl)benzene-1,3-diols

Abstract  

A one-pot synthesis of new biologically active 4- and 6-(1-alkyl/aryl-1H-benzimidazol-2-yl)benzene-1,3-diols has been developed. The compounds were obtained by the reaction of aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione] with N-substituted benzene-1,2-diamines. Elemental analysis, IR, ¹H NMR, ¹³C NMR, and mass spectral data were used to elucidate their structures. The developed method offers short reaction times, easy and quick isolation of the products, and good yields. The antiproliferative properties of the synthesized compounds were investigated against a panel of human cancer cell lines. Some of the tested compounds showed significant cytotoxic activity.     

Synthesis,Biological Evaluation,and Molecular Docking Studies of Some N‐thiazolyl Hydrazones and Indenopyrazolones

Two new series of N‐thiazolyl hydrazones ( 3a – h ) and indenopyrazolones ( 4a – h ) were synthesized by the reaction of various 2‐acyl‐(1H)‐indene‐1,3(2H)‐diones, thiosemicarbazide, and phenacyl bromide/substituted phenacyl bromides. The in vitro antimicrobial activity of these synthesized compounds was assayed against four bacteria, namely, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, and two fungi, namely, Candida albicans and Aspergillus niger, by employing serial dilution method. Ciprofloxacin and fluconazole were used as antibacterial and antifungal reference drugs, respectively. Results of antimicrobial assay showed that the tested compounds have broad range of activity. The compounds 3h and 4a against C. albicans displayed more potency than fluconazole whereas 3b and 3c against B. subtilis showed activity comparable with ciprofloxacin. The synthesized indenopyrazolones ( 4a – h ) were evaluated for their in vitro antioxidant activity by 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging assay using ascorbic acid as reference. Compound 4b exhibited the highest 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging with IC₅₀ value 33.14 μg/mL. The observed results of antimicrobial activity were supported by molecular docking study performed to understand the binding interaction of hydrazones ( 3a – h ) and indenopyrazolones ( 4a – h ) with lanosterol 14α‐demethylase.     

Novel acenaphthopyrazine derivatives as antitumor agents against MCF-7 cells: molecular synthesis, optical properties, and DNA-binding studies

Abstract  

A series of novel acenaphthopyrazine derivatives was synthesized from acenaphthylene-1,2-dione via three steps, including bromination, cyclization, and S_NAr^H reaction. These new compounds exhibited potential antiproliferative activity against MCF-7 cells in vitro, and 3-[2-(dimethylamino)ethylamino]acenaphtho[1,2-b]pyrazine-8,9-dicarbonitrile exhibited the highest activity (IC ₅₀ = 4.60 μM). DNA-binding experiments suggested that these derivatives bind to DNA through intercalation with intrinsic binding constants K all above 10⁵ M⁻¹. Optical property studies indicated that these compounds have long emission wavelength (λ _em > 560 nm), high quantum yields in toluene (Φ_f = 0.59 for 3-(morpholin-4-yl)acenaphtho[1,2-b]pyrazine-8,9-dicarbonitrile), and large Stokes shift (ΔS > 130 nm).     

CoMFA and CoMSIA studies on a new series of xanthone derivatives against the oral human epidermoid carcinoma (KB) cancer cell line

Abstract  

A new series of xanthone derivatives against the oral human epidermoid carcinoma (KB) cancer cell line is examined to determine the relationship between the structural properties and the biological activity of these compounds—the 3-D quantitative structure–activity relationship (3D-QSAR)—using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The best CoMFA and CoMSIA models were obtained using the atom-based alignment of 33 compounds, 22 training compounds and 11 tested compounds, and these give desirable statistics; those for the CoMFA standard model were: r _cv² = 0.691, r ² = 0.998, S _press = 0.178, s = 0.014 and F = 1080.765, while CoMSIA combined steric, electrostatic, hydrophobic and hydrogen-bond acceptor fields: r _cv² = 0.600, r ² = 0.988, S _press = 0.206, s = 0.034 and F = 284.433. The 3D-QSAR models calculated satisfactory test set activities. The 3D-QSAR contour plots correlated strongly with the experimental data for the binding topology. For this reason, these results would be beneficial for predicting affinities with the compounds of interest, and they are advantageous for guiding the design and synthesis of new and more effective anticancer agents.     

The synthesis of azole derivatives from 3-[(4-methylphenyl)amino]propanehydrazide and its N′-phenylcarbamoyl derivatives, and their antibacterial activity

Abstract  

5-[2-[(4-Methylphenyl)amino]ethyl]-1,3,4-oxadiazol-2(3H)-thione, 5-[2-[(4-methylphenyl)amino]ethyl]-1,3,4-oxadiazol-2(3H)-one, N-(2,5-dimethyl-1H-pyrrol-1-yl)-3-[(4-methylphenyl)amino]propanamide, and a series of N-[(phenylcarbamoyl)amino]-3-[(4-methylphenyl)amino]propanamides and 3-[(4-methylphenyl)(phenylcarbamoyl)amino]-N-[(phenylcarbamoyl)amino]propanamides, and their thio analogues were synthesized from 3-[(4-methylphenyl)amino]propanehydrazide. 1,3,4-Oxadiazole-2(3H)-thione was converted to 4-amino-2,4-dihydro-5-[2-[(4-methylphenyl)amino]ethyl]-3H-1,2,4-triazole-3-thione, whereas cyclization of N′-phenylcarbamoyl derivatives provided thiazole, oxadiazoles, and thiadiazole, as well as triazole derivatives. Two of the synthesized compounds exhibited good antibacterial activity against Rhizobium radiobacter.     

SARs of the antiprotozoal action of 6,7-diaryl-bicyclo[2.2.2]octan-2-ols

Abstract  

Several 4-amino-6,7-diarylbicyclo[2.2.2]octan-2-ols bearing varying substituents on the aromatic rings were synthesized following a manual method for applying the Hansch approach. All new compounds were tested for their activity against the causative organisms of East African sleeping sickness and malaria tropica. Structure activity relationships are discussed.     

A facile one-pot synthesis of 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones

Abstract  

The reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one or its 2-methylthio derivative with hydrazonoyl halides, in the presence of triethylamine, yielded 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The structure of the latter compounds was further confirmed by reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one with the appropriate active chloromethylenes followed by coupling of the products with benzenediazonium chloride to afford the non-isolable azo-coupling products which converted, in situ, to 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The reaction mechanism was proposed and the products were screened for their biological activity. Some of the newly synthesized compounds had a moderate effect against some bacterial and fungal species.