Synthesis of certain 2-substituted-1H-benzimidazole derivatives as antimicrobial and cytotoxic agents

A series of 2-substituted-1H-benzimidazole derivatives were synthesized and evaluated for antimicrobial, antifungal and cytotoxic activities. The results showed that all tested compounds showed potent antimicrobial activity against some species of Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi) and fungi (Candida albicans) with minimum inhibitory concentrations (MICs) lower than 0.016 μg/mL. In contrast, all tested compounds were inactive against Staphylococcus aureus (Gram-positive bacterium). The final targets were also tested for their antitumor activity in vitro on cervical carcinoma (HeLa) cell line. Eight of the test compounds displayed more potent cytotoxic effect than doxorubicin at nanomolar concentrations. Compounds 2c and 3c exerted the strongest cytoyoxic effect with IC(50) 15 and 13 nM, respectively.     

Facile and simple synthesis of some new polyfunctionally heterocyclic derivatives incorporating 2‐imino‐2H‐chromene moiety

1,2‐Dihydro‐2‐imino‐6‐(2‐imino‐2H‐chromen‐3‐yl)‐1,4‐diphenyl‐pyridine‐3‐carbonitrile 4 has been synthesized and reacted with ethyl cyanoacetate to yield the new 5‐amino‐1,7‐dihydro‐2‐(2‐imino‐2H‐chromen‐3‐yl)‐7‐oxo‐1,4‐diphenyl‐1,8‐naphthyridine‐6‐carbonitrile 6 , which consider a good and available starting intermediate for synthesis of series of functionalized chromenes. So, the compound 6 was utilized as a key for the synthesis of some new pyrimido[5,4‐c][1,8]naphthyridinones, pyrido[2,3‐c][1,6]naphthyridinones, triazolo[3′,4′:1,6]triazino][5,4‐c][1,8]naphthyridinones, triazolo[2′,3′:1,6]pyrimido[4,5‐c][1,8]naphthyridinones, triazepino[6,5‐c][1,8]naphthyridinone, and triazino[5,4‐c][1,8]naphthyridinones. The structures of these compounds were established by elemental analysis, IR, MS, and NMR spectral analysis. J. Heterocyclic Chem., (2012).     

Efficient synthesis of pyrimido[5,4‐c]pyridazines and of thiino[2,3‐d]pyrimidines based on an aza‐wittig reaction/heterocyclization strategy

A simple one‐pot and efficient method is described for the synthesis of pyrimido[5,4‐c]pyridazines 5 and of thiino[2,3‐d] pyrimidines 15 by a domino process involving an aza‐Wittig reaction/heterocyclization. The iminophosphorane 2 reacted with phenylisocyanate, followed by heterocyclization on addition of amines to give the corresponding guanidine intermediates 4 . The guanidine intermediates were cyclized in the presence of catalytic amount of sodium ethoxide to pyrimido[5,4‐c]pyridazines 5 . Similarly, iminophosphorane 12 reacted with phenylisocyanate and amines to give thiino[2,3‐d]pyrimidines 15 in moderate yields. Furthermore, pyridazino[4,3‐d]oxazines 10 and thiino[2,3‐d]oxazines 19 were synthesized by the intremolecular aza‐Wittig reaction of phosphazenes 2 and 12 , respectively, with acid chlorides followed by heterocylization via imidoyl chloride intermediates. J. Heterocyclic Chem., (2012).     

NADH oxidation using modified electrodes based on lactate and glucose dehydrogenase entrapped between an electrocatalyst film and redox catalyst-modified polymers

We have developed a simple and efficient method for the enhanced loading of silver nanoparticles onto carbon nanospheres, and how this method can be used to design an electrochemical sensor for hydrogen peroxide (HP). A glassy carbon electrode was modified with hemoglobin, carbon nanospheres, and by enhanced loading of silver nanoparticles onto the carbon nanospheres via spontaneous polymerization of dopamine. The hemoglobin exhibits a remarkable electrocatalytic activity for the reduction of HP. The electrochemical response to HP is linear range in the 1.0–147.0?μM concentration range, with a detection limit of 0.3?μM at a signal-to-noise ratio of 3.

Dynamical Localization in Disordered Quantum Spin Systems

We say that a quantum spin system is dynamically localized if the time-evolution of local observables satisfies a zero-velocity Lieb-Robinson bound. In terms of this definition we have the following main results: First, for general systems with short range interactions, dynamical localization implies exponential decay of ground state correlations, up to an explicit correction. Second, the dynamical localization of random xy spin chains can be reduced to dynamical localization of an effective one-particle Hamiltonian. In particular, the isotropic xy chain in random exterior magnetic field is dynamically localized.     

Synthesis,Characterization, In Vitro Anticancer Potentiality,and Antimicrobial Activities of Novel Peptide–Glycyrrhetinic-Acid-Based Derivatives

Glycyrrhetinic acid (GA) is one of many interesting pentacyclic triterpenoids showing significant anticancer activity by triggering apoptosis in tumor cell lines. This study deals with the design and synthesis of new glycyrrhetinic acid (GA)–amino acid peptides and peptide ester derivatives. The structures of the new derivatives were established through various spectral and microanalytical data. The novel compounds were screened for their in vitro cytotoxic activity. The evaluation results showed that the new peptides produced promising cytotoxic activity against the human breast MCF-7 cancer cell line while comparing to doxorubicin. On the other hand, only compounds 3, 5, and 7 produced potent activity against human colon HCT-116 cancer cell line. The human liver cancer (HepG-2) cell line represented a higher sensitivity to peptide 7 (IC₅₀; 3.30 μg/mL), while it appeared insensitive to the rest of the tested peptides. Furthermore, compounds 1, 3, and 5 exhibited a promising safety profile against human normal skin fibroblasts cell line BJ-1. In order to investigate the mode of action, compound 5 was selected as a representative example to study its in vitro effect against the apoptotic parameters and Bax/BCL-2/p53/caspase-7/caspase-3/tubulin, and DNA fragmentation to investigate beta (TUBb). Additionally, all the new analogues were subjected to antimicrobial assay against a panel of Gram-positive and Gram-negative bacteria and the yeast candida Albicans. All the tested GA analogues 1–8 exhibited more antibacterial effect against Micrococcus Luteus than gentamicin, but they exhibited moderate antimicrobial activity against the tested bacterial and yeast strains. Molecular docking studies were also simulated for compound 5 to give better rationalization and put insight to the features of its structure.     

A Convenient and Efficient Conversion of 4‐Aminobenzophenone into Some New 1,2,3‐Triazole and Benzothiazole Derivatives

Several heterocyclic systems such as 1,2,3‐triazoles ( 5–9 ), pyrimidotriazoles ( 10–13 ), benzothiazole ( 16 ), thiazolo ( 17 ), and pyrimidinone derivative ( 18 ) was obtained from 4‐aminobenzophenone ( 1 ) and the appropriate reagents.     

Kinetics and mechanism of the oxidation of diaqua(nitrilotri- acetato)chromium(III) complex by N-bromosuccinimide

The kinetics of oxidation of the diaqua(nitrilotriacetato)chromium(III) complex [CrIIInta(H2O)2], by N-bromosuccinimide (NBS) to chromium(VI) in aqueous solution obeys the equation: where k1 is the rate constant for the electron-transfer process, K1 the equilibrium constant for the dissociation of [CrIIInta(H2O)2] to [CrIIInta(H2O)(OH)]−, and K2 is the pre-equilibrium formation constant for the precursor complex [CrIIInta(OH)(NBS)]−. The thermodynamic activation parameters were calculated and it is proposed that electron transfer proceeds via an inner-sphere mechanism. This revised version was published online in June 2006 with corrections to the Cover Date.     

On-line elimination of spectral interference of iron matrix in the flame atomic absorption determination of zinc by anion-exchange separation

A flow injection analysis (FIA) system has been developed for the flame atomic absorption spectroscopic (FAAS) determination of zinc in iron matrix. The spectral line interference of iron at 213.859 nm was eliminated by on-line separation using a micro-column of strong anion-exchange resin (Dowex 1-X8). The zinc chloro complexes were retained from 2 M HCl solution while most of the iron chloro complexes were passed to waste. For a 2% iron solution, matrix removal efficiency was 98.2% which means that positive spectral line interference of iron at the Zn line was reduced from 0.42 to 0.008 μg ml⁻¹ Zn. The optimized flow injection system can handle up to 48 samples with good precision (less than 3.5% relative standard deviation (R.S.D.)) in the working range of 0.075-2.2 μg ml⁻¹ Zn. Comparative analysis of a certified reference material and synthetic sample solutions containing traces of Zn in 2% Fe by the proposed method and by graphite furnace atomic absorption spectroscopy (GFAAS) showed no evidence of analytical bias at the 95% confidence level.     

Kinetics and mechanism of oxidation in the diaqua(nitrilotriacetato)cobaltate(II)/N-bromosuccinimide reaction: evidence for iron(II) catalysis

Summary Oxidation of the diaqua(nitrilotriacetato)cobaltate(II) complex, [CoIInta(H2O)2]-, by NBS has been studied in aqueous medium. The kinetics of the reaction in the presence of an iron(II) catalyst obey the rate law: Catalysis by iron(II) is believed to be due to the oxidation of iron(II) to iron(III), which acts as the oxidizing agent. The thermodynamic activation parameters were calculated and we propose that electron transfer proceeds through an inner-sphere mechanism. This revised version was published online in June 2006 with corrections to the Cover Date.