Hybrid 4‐Aminoquinoline‐1,3,5‐triazine Derivatives: Design,Synthesis, Characterization,and Antibacterial Evaluation

A series of novel 4‐aminoquinoline 1,3,5‐triazine derivatives were synthesized and characterized by FTIR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analysis. The antibacterial activities of synthesized compounds were tested against three Gram‐positive bacteria, namely Bacillus subtilis (NCIM‐2063), Bacillus cereus (NCIM‐2156), and Staphylococcus aureus (NCIM‐2079), and four Gram‐negative bacteria, namely Proteus vulgaris (NCIM‐2027), Proteus mirabilis (NCIM‐2241), Escherichia coli (NCIM‐2065), and Pseudomonas aeruginosa (NCIM‐2036), using ciprofloxacin as reference standard drug. Results showed compound 9a and 9e as potent antibacterial agents against all bacterial strains except Bacillus cereus (NCIM‐2156). Copyright © 2014 HeteroCorporation     

A New Nortriterpene from the Root of Celastrus hypoleucus

A new nortriterpene, 2‐hydroxy‐3‐methyl‐21‐oxo‐12,24‐dinor‐D : B‐friedooleana‐1,3,5(10),7‐tetraen‐29‐oic acid ( 1 ), was isolated from the root of Celastrus hypoleucus, together with the two known compounds, celastorol ( 2 ) and pristimerine ( 3 ). Their structures were elucidated on the basis of spectroscopic analyses. Compounds 1 – 3 exhibited in vitro significant antioxidant (against lipid peroxidation; by the TBARS method) and antitumor activities (against cancer cell lines P‐388, A‐549, HL‐60, and BEL‐7402).     

Synthesis of Some New 2-(4-Methoxybenzothiazol-2′-yl amino)-4-(2-chloro-4-trifluoromethylanilino)-6-(substituted thioureido)-1,3,5-triazine as Antifungal Agents

2,4,6-Trichloro 1,3,5-triazine was selectively reacted with new nucleophilic reagents such as 4-methoxy-2-aminobenzothiazole, 2-chloro-4-trifluoromethyl-aniline, and phenylsubstituted thiourea in alkaline medium to give 2-(4-methoxybenzothiazol-2′-ylamino)-4-(phenylthioureido)-6-(substitutedthioureido)-1,3,5-triazines. The structures of these compounds were confirmed by IR, ¹H NMR, ¹⁹F NMR, mass spectral data, and elemental analysis. The compounds show fungicidal activity against Alternaria alternata, Aspergillus niger, and Macrofomina.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Bacteriostatic activities of N-substituted tris-thioureas bearing amino acid and aniline substituents

A series of tri-substituted thiourea derivatives were synthesized by the reaction of 1,3,5-triacetylbenzoyl isothiocyanate with aminoacids and aniline derivatives. All thiourea derivatives were characterized by FT-IR, ¹H and ¹³C NMR spectroscopy. Antibacterial activities against wild-type Escherichia coli American Type Culture Collection 8739 were determined by use of the turbidimetric methodto evaluate the effect of varying amino groups on the synthesized thioureas. Tris-thiourea derivatives bearing ortho-chloroaryl substituents showed excellent antibacterial activity against E. coli with minimal inhibitory concentration (MIC) of 96 ppm. The optimum inhibition was dependent on the type of amines and the position of the halogen in aniline.     

Fe(III) Complexes Based on Mono- and Bis-pyrazolyl-s-triazine Ligands: Synthesis,Molecular Structure,Hirshfeld, and Antimicrobial Evaluations

The self-assembly of iron(III) chloride with three pyrazolyl-s-triazine ligands, namely 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazine (^PipBPT), 4-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-yl)morpholine (^MorphBPT), and 4,4’-(6-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazine-2,4-diyl)dimorpholine (^bisMorphPT) afforded [Fe(^PipBPT)Cl₂][FeCl₄] (1), [Fe(^MorphBPT)Cl₂][FeCl₄] (2), and [H(^bisMorphPT)][FeCl₄]. ^bisMorphPT.2H₂O (3), respectively, in good yield. In complexes 1 and 2, the Fe(III) is pentacoordinated with three Fe-N interactions from the pincer ligand and two coordinated chloride anions in the inner sphere, and FeCl₄¯ in the outer sphere. Complex 3 is comprised of one protonated ligand as cationic part, one FeCl₄¯ anion, and one neutral ^bisMorphPT molecule in addition to two crystallized water molecules. Analysis of molecular packing using Hirshfeld calculations indicated that H…H and Cl…H are the most important in the molecular packing. They comprised 40.1% and 37.4%, respectively in 1 and 32.4% and 37.8%, respectively in 2. Complex 1 exhibited the most bioactivity against the tested microbes while 3 had the lowest bioactivity. The ^bisMorphPT and ^MorphBPT were inactive towards the tested microbes while ^PipBPT was active. As a whole, the Fe(III) complexes have enhanced antibacterial and antifungal activities as compared to the free ligands.     

Chemistry of new dimethyl-benzo,-1,3,6-oxadiazepine and 1,3,5-triazepine derivatives as anticancer agents

A series of novel substituted 2,4-dimethyl-benzo[f][1,3,5] triazepine, such as 2-thioxopyrimidinone(4), 2-oxopyridine-3-carbonitrile(6), benzamide(8), N’-(6-oxopyrimidine)benzohydrazide(10), 1-(4-(1,3,4-oxadiazole)thiophene)ethan-one(12), 1-(4-methylthiophene-3-carbonyl)pyrazolidine-dione(14), 1-(4-(pyrazole-carbonyl)-3-methylthiophene)ethanone(16), ethyl dimethylthieno[2,3-b]pyridine-2-carboxylate (18), and 2-thioxo-thieno[2,3-d]pyrimidinone(20) derivatives, were synthesized from 2,4-dimethyl benzo[d] [1,3,6] oxadiazepine (2). The structures of these newly synthesized compounds were established on the basis of their spectral data and elemental analysis. These compounds were also screened for their anti-tumor activities. Some of the prepared compounds showed promising activities for example; benzotriazepine, thienopyrimidine, oxadiazole, and thiophene moiety displayed cytotoxic activity.     

Silver(I)‐N‐heterocyclic carbene complexes of bis‐imidazol‐2‐ylidenes having different aromatic‐spacers: synthesis,crystal structure,and in vitro antimicrobial and anticancer studies

A series of Ag(I) complexes ( 6 , 7 , 8 , 9 ) derived from imidazol‐2‐ylidenes was synthesized by reacting Ag₂O with an o‐, m‐, p‐xylyl or 1,3,5‐triazine‐linked imidazolium salts ( 1 , 2 , 3 , 4 ) and then characterizing these using various spectro‐analytical techniques. Additionally, triazine‐linked bis‐imidazolium salt 5 was characterized using the single‐crystal X‐ray diffraction method. Complexes 6–9 were formed from the N‐heterocyclic carbene ligand precursors 1–3 as PF₆^‐ salts in good yields. Conversely, salt 5 does not form Ag(I) complex even under various reaction conditions. Using ampicillin as a standard, complexes 6–9 were tested against bacteria strains Escherichia coli and Staphylococcus aureus as Gram‐negative and Gram‐positive bacteria, respectively, showing potent antimicrobial activities against the tested bacteria even at minimum inhibition concentration and bacterial concentration levels. Furthermore, the potential anticancer activities of the reported complexes were evaluated against the human colorectal cancer (HCT 116) cell lines, using 5‐fluorouracil as a standard drug. The highest anticancer activities were observed for complex 8 with an IC₅₀ value of 3.4 μm , whereas the lowest was observed for complex 9 with an IC₅₀ value of 18.1 μm . Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis,insecticidal activities,and molecular docking studies of 1,5‐disubstituted‐1,3,5‐hexahydrotriazine‐2‐(N‐nitro)imines

A series of novel neonicotinoids analogs were designed by modifying the pharmacophore of imidacloprid to 1,3,5‐hexahydrotriazine conjugated to nitroimine (?NNO₂) and introducing the phenyl or arylmethyl at the 5‐position, and their insecticidal activities were evaluated. Introducing a heterocyclic methyl at 5‐position increased the insecticidal activities, whereas other phenyl, phenylmethyl or phenylethyl substituents were unfavorable to activities. Molecular docking study was also performed to clarify the interactions of the most potent analog 1‐((6‐chloropyridin‐3‐yl)methyl)‐5‐(3‐pyridylmethyl)‐1,3,5‐hexahydrotriazine‐2‐(N‐nitro) imine ( 7s ) with the target nicotinic acetylcholine receptor, which explained the structure‐activity relationships observed in vitro, and revealed further possibilities for insecticide development. J. Heterocyclic Chem., (2011).     

Synthesis,antioxidant, and anticholinesterase activities of novel N-arylsulfonyl hydrazones bearing sulfonate ester scaffold

In this research, two new series of N-arylsulfonyl hydrazone compounds ( 14 – 25 ) possessing a sulfonate moiety were synthesized and characterized by elemental analysis and various spectroscopic techniques including fourier transform infrared (FT-IR), ¹H-, and ¹³C nuclear magnetic resonance (NMR). These compounds synthesized as target molecules ( 14 – 25 ) were tested for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition activities and antioxidant potential. The antioxidant capacities of the tested molecules were determined by four different assays. The IC₅₀ values of the screened molecules were determined in the range of 60.14 ± 0.25–84.81 ± 1.09 μM against AChE and in the range of 70.11 ± 0.67–93.60 ± 0.47 μM against BChE. In the AChE assay, 4-hydroxybenzaldehyde-based compound 25 (60.14 ± 0.25 μM) showed the highest activity in comparison to rivastigmine (501 ± 3.08 μM). This compound (71.42 ± 0.19 μM) is also one of the compounds with the highest activity against BChE. In the BChE assay, 2-hydroxybenzaldehyde-based compound 19 (70.11 ± 0.67 μM) indicated the highest activity in comparison to rivastigmine (19.95 ± 0.20 μM). In antioxidant activity studies, the tested molecules showed lower activities than the standard compounds (butylated hydroxytoluene and α-tocopherol). Consequently, some novel compounds can be used as potential inhibitor candidates in future studies.     

Photopolymerization reactions initiated by a visible light photoinitiating system: Cyanine dye/borate salt/1,3,5‐triazine

New three‐component photoinitiating systems consisting of a cyanine dye, borate salt, and a 1,3,5‐triazine derivative were investigated by measuring their photoinitiation activities and through fluorescence quenching experiments. Polymerization kinetic studies based on the microcalorimetric method revealed a significant increase in polymerization rate when the concentration of n‐butyltriphenylborate salt or the 1,3,5‐triazine derivative were increased. The photo‐induced electron transfer process between electron donor and electron acceptor was studied by means of fluorescence quenching and SrEt change of the fluorescence intensity. The experiments performed documented that an increase of the n‐butyltriphenylborate salt concentration dramatically increases the rate of dye fluorescence quenching, whereas the increasing of the 1,3,5‐triazine derivative concentration slows down the consumption of the dye. We conclude that the primary photochemical reaction involves an electron transfer from the n‐butyltriphenylborate anion to the excited singlet state of the dye, followed by the reaction of the 1,3,5‐triazine derivative with the resulting dye radical to regenerate the original dye. This reaction simultaneously produces a triazinyl radical anion derived from the 1,3,5‐triazine, which undergoes the carbon‐halogen bond cleavage yielding radicals active in initiation of a free radical polymerization chain. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3626–3636, 2007     

Hydroxyethyl curdlan as a novel water soluble derivative: Synthesis,characterization, and antioxidant capacity

In this study, hydroxyethyl curdlans (HeCDs) with different molecular weights were successfully fabricated. The structure and properties of the synthesized HeCDs were measured by FTIR, ¹³C nuclear magnetic resonance (NMR), and Raman spectroscopy and compared with curdlan. The degree of crystallinity of HeCDs was measured with X-ray diffractometry (XRD). Differential scanning calorimetry and thermogravimetric analysis were performed to determine thermal properties of HeCs. Solubility of HeCDs was tested in water, common organic solvents, and NaOH solution. Antioxidant activities of HeCs were investigated using various in vitro assay systems. The HeCDs exhibited a dose-dependent free radical scavenging activity as shown by their DPPH radical, ABTS radical and superoxide anion radical inhibition, and ferrous chelating ability and reducing power. The improved water solubility property and antioxidant activity of these curdlan derivatives could have a wide range of applications, particularly its use as an antioxidant in food, food packaging, biomedical, and pharmaceutical industries.     

Synthesis,characterization, and antimicrobial activities of nickel(II) and copper(II) Schiff-base complexes

Ni(II) and Cu(II) metal complexes of simple unsymmetrical Schiff-base ligands derived from salicylaldehyde/5-methylsalicylaldehyde and ethylenediamine or diaminomaleonitrile (DMN) were synthesized. The ligands and their complexes were characterized by elemental analysis, ¹H NMR, FT IR, and mass spectroscopy. The electronic spectra of the complexes show d–d transitions in the region at 450–600 nm. Electrochemical studies of the complexes reveal that all mononuclear complexes show a one-electron quasi-reversible reduction wave in the cathodic region. ESR spectra of the mononuclear copper(II) complexes show four lines, characteristic of square-planar geometry, with nuclear hyperfine spin 3/2. The copper(II) complexes show a normal room temperature magnetic moment value μ _eff = 1.70–1.74 BM which is close to the spin only value of 1.73 BM. Kinetic studies on the oxidation of pyrocatechol to o-quinone using the copper(II) complexes as catalysts were also carried out. The in vitro antimicrobial activity of the investigated compounds was tested against human pathogenic bacterias such as Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumonia, Pseudomonas aeruginosa and Escherichia coli. The antifungal activity was tested against Candida albicans. Generally, the metal complexes have higher antimicrobial activity than the free ligands.     

Proposed Mechanism for Microbial Degradation of Polyacrylate

Abstract

A possible aerobic degradation mechanism for polyacrylate (PA) was examined with acrylic oligomer-utilizing bacteria (Microbacterium sp., Xanthomonas maltophilia, and Acinetobacter sp.), using a model compound (1,3,5-pentane tricarboxylic acid, PTCA). Acyl-coenzyme A synthetase activities were detected with dialyzed cell-free extracts of PTCA-utilizing bacteria toward PTCA, PA 500, and PA 1000. This result suggested that PA is activated by coenzyme A and metabolized via PA-coenzyme A. Metabolic products formed from PTCA were detected in culture filtrates and reaction mixtures of washed cells. Fraction A was detected as a main metabolite by high-performance liquid chromatography. A small amount of fraction B was concomitant with fraction A. Also, another fraction, C, was detected. These intermediate metabolites were characterized by LC-MS as 1,3,5-(1- or 2-pentene)tricarboxylic acid for fractions A and B and as 1,3,5-(2-oxopentane)tricarboxylic acid for fraction C. Fraction A was metabolized far faster than fraction B. Fraction B was thought to be an artifact formed from fraction A under alkaline conditions. Thus PTCA and also PA seemed to be metabolized by the mechanism similar to β-oxidation of fatty acids. The degradation of PTCA by washed cells was slower than that by growing cells and was inhibited by 5 mM NaN₃. This suggests that the metabolism is linked to a respiratory chain of bacteria.     

Synthesis of 3,5-disubstituted 1-amino-1,3,5-triazine-2,4,6-triones (or 1-aminocyanurates) by cyclic transformation of 1,3,4-oxadiazol-2(3H)-one derivatives

The 5-aryl(or methyl)-3-phenylcarbamoyl-1,3,4-oxadiazol-2(3H)-ones 2 , in the presence of sodium hydride in anhydrous dimethylformamide, were transformed into 1-benzamido(or acetamido)-3,5-diphenyl-1,3,5-triazine-2,4,6-trione derivatives 7 in poor yields. However, compounds 7 were obtained in better yields when the sodium salts of 5-aryl(or methyl)-1,3,4-oxadiazol-2(3H)-ones 1 were treated with two equivalents of aryl(or ethyl)isocyanates. Acidic hydrolysis of 1-acetamido-3,5-diphenyl-1,3,5-triazine-2,4,6-trione ( 7i ) provided the corresponding free N-amino derivative 9 . Nitrous deamination of 9 gave the known 3,5-diphenyl-1,3,5-triazine-2,4,6-trione ( 11 ). This cyclic transformation is the first one to be reported providing 1,3,5-triazine-2,4,6-trione derivatives.     

PEG-400 mediated an efficient eco-friendly synthesis of new isoxazolyl pyrido[2,3-d]pyrimidines and their anti-inflammatory and analgesic activity

Abstract

Polyethylene glycol-400 (PEG-400) has been developed as an efficient and eco-friendly reaction medium for the synthesis of new isoxazolyl pyrido[2,3-d]pyrimidine derivatives 11 from isoxazolyl cyanoacetamide synthon 7. Compound 7 was employed with various aromatic aldehydes 8 and malononitrile 9 in the presence of triethylamine (Et₃N) to afford the corresponding (E)-6-amino-1-(3-methyl-5-styrylisoxazol-4-yl)-2-oxo-4-phenyl-1,2-dihydro- pyridine-3,5-dicarbonitrile 10 at room temperature by using PEG-400 as a solvent medium as well as catalyst. The intermediate 10 on treatment with thiourea in the presence of PEG-400 at 90?°C to give the target compounds isoxazolyl pyrido[2,3-d]pyrimidines 11 in good to excellent yields. The newly synthesized compounds 10 and 11 were characterized by IR, ¹H NMR, ¹³C NMR, and HRMS analysis. The target compounds 11a-x was screened for their anti-inflammatory and analgesic activities. Among the tested compounds, the compounds 11s, 11t, 11u, 11v, 11w, and 11x showed significant anti-inflammatory and potent analgesic activities as that of reference drugs. The advantages of this protocol are operational simplicity, catalyst free, environmental safety, wide substrate scope, good yields, and PEG-400 can be recovered and reused. Most significant of all, this protocol is green.     

Preparation,Characterisation, and Structure of N-Methylated Derivatives of 1,3,5-Triamino-1,3,5-trideoxy-cis-inositol: Polyalcohols with Unusual Acidity

1,3,5-Trideoxy-1,3,5-tris(dimethylamino)-cis-inositol (TDCI) and 1,3,5-trideoxy-1,3,5-tris(trimethylammonio)-cis-inositol (TTCI) were prepared by methylation of 1,3,5-triamino-1,3,5-trideoxy-cis-inositol (TACI). The ability of TDCI to form both intermolecular and intramolecular H-bonds, as demonstrated by X-ray diffraction, is probably responsible for the good solubility of TDCI in almost every common solvent. TTCI was found to be a polyol of unusual high acidity (pK₁ = 8.14 ± 0.02, pK₂ = 13.0 ± 0.2). This phenomenon could be explained by electrostatic interactions between the charged substituents of the cyclohexane residue.     

Synthesis and Insecticidal Activities of 1,3,5‐Trisubstituted‐1,3,5‐hexahydrotriazine‐2‐N‐nitroimines

A new series of 1,3,5‐trisubstituted‐1,3,5‐hexahydrotriazine‐2‐N‐nitroimines ( 3a – 3j ) were designed and synthesized as novel neonicotinoid analogues, and their structures were characterized by ¹H NMR, IR, elemental analysis and MS. The preliminary bioassay tests showed that most of the target compounds had good insecticidal activities against Nilaparvata lugens as well as Aphis medicaginis at 500 mg/L, while compound 3i had 100% mortality against Nilaparvata lugens at 20 mg/L.     

Chemical composition,antioxidant and antiproliferative activities of essential oil from rhizome and leaves of Curcuma mutabilis Škorničk., M. Sabu & Prasanthk., endemic to Western Ghats of India

Abstract

Hydro-distilled essential oils, from fresh rhizomes and leaves of Curcuma mutabilis ?korni?k., M.Sabu & Prasanthk., characterized by GC–MS revealed the presence of thirty three and twenty three compounds therein respectively. Whilst estrone methyl ether (3-Methoxyestra-1,3,5(10)-trien-17-one) was the major component in rhizome oil (47.35%), sesquiterpene hydrocarbons predominated as the major group (63.92%) in leaf oil with a higher preponderance of β-caryophyllene (25.48%), β-farnesene (19.47%) and α-humulene (11.01%). Weak antioxidant activities observed in these oils determined by DPPH and ABTS methods were apparently influenced both by the oil composition and the assay conditions. Rhizome oil showed higher antiproliferative activity than leaf oil against leukemic K562 (IC₅₀-6.8µg/mL) and colorectal HCT116 (IC₅₀-8.5µg/mL) cancer cell lines. This first report reveals composition and biological activities of essential oils from C. mutabilis.     

Synthesis,antifungal and antibacterial activity of calix[4]arene-based 1,3,4-oxadiazole derivatives

We describe the synthesis of some novel p-tert-butylcalix[4]arene-based (5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate derivatives ( 4a–e ). These compounds were synthesized by the reaction of tetra-tert-butyl calix[4]arene ( 1 ) with (5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate ( 3a–e ) in the presence of potassium carbonate as a weak base and dry acetone as the solvent. All the newly synthesized calix[4]arene derivatives were characterized by elemental analysis and various spectroscopic methods such as FT-IR, ¹H NMR,¹³C NMR, DEPT, and ESI-MS. The synthesized compounds were tested in vitro for their antibacterial and antifungal activities against Escherichia coli and Aspergillus fumigates in comparison with enrofloxacin and amphotericin as reference drugs, which are normally used for treating such infections. The synthesized compounds showed different inhibition zones against the tested bacteria and fungi. Compound 4c was found to be most effective against A. fumigates, whereas compound 4e was found to be equally effective against E. coli and A. fumigates.     

Synthesis of Some N-Alkoxycarbonyl-N″-benzoyl-benzamidrazones（p-toluamidrazones） and 1,3,5-Trisubstituted 1,2,4-Triazole Derivatives from N-Benzoylimidates and their Antimicrobial and Anticancer Screening Studies

Some new N-alkoxycarbonyl-N″-benzoyl-benzamidrazones （p-toluamidrazones） 3a-3d, and 1,3,5-trisubstituted 1,2,4-triazole 4a-4h derivatives by starting from N-benzoylbenzimidates or N-benzoyl-p-toluimidates. The structures of compounds 3 and 4 were established on the basis of elemental analyses, IR, ^1H NMR, ^13C NMR and UV data. Antimicrobial experiments of the compounds performed by using agar-well diffusion and broth microdilution methods revealed that only compounds 3a-3d, 4a and 4b showed inhibitory effect only on Candida albicans ATCC 60193. However, compound 4b had also specific antibacterial activity against Staphylococcus aureus ATCC 25923. The other compounds showed neither antifungal nor antibacterial activities. Compounds 3a, 4a and 4b have been screened on three human tumor cell lines, breast cancer （MCF7）, non small cell lung cancer （NCI-H460）, and CNS cancer （SF-268） at the National Cancer Institute （NCI）, USA, which were found to exhibit low antiproliferative activity.