Some novel triaza Schiff base metal(II) complexes were synthesized and characterized by various spectral techniques. The synthesized compounds were screened for their in vitro antibacterial activity. ...The stoichiometries and formation constants of complexes were determined spectrophotometrically. Density functional theory calculations at different level of DFT and basis set were carried out to investigate the optimized geometry of the ligands and their complexes.
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•Metal (II) Schiff base complexes containing N3 donor system were synthesized.•Spectrophotometric methods were applied to explain the complex formation.•The optimized geometrical parameters were obtained using by DFT calculations.•The antibacterial activity of the synthesized compounds was screened.
Some novel Ni(II), Cu(II) and Zn (II) metal complexes with new triaza Schiff base ligand (N-(2quinolylmethylidene)-4X-2-aminobenzene)imine (where X = Me, Cl, NO2)) have been synthesized. Various spectral techniques such as elemental analysis, magnetic susceptibility, conductivity, 1HNMR, IR, UV–Vis spectra, Mass spectrometry, powder XRD and EDX were used to confirm the structures. It has been found that the Schiff base behaves as a tridentate ligand forming chelates with 1:1 metal:ligand stoichiometry. The prepared Schiff base compounds were screened in vitro for their antibacterial activity against a number of pathogenic Gram positive and Gram negative bacteria, namely S.aureas and E.coli. The complexes show more potent activities than their free ligands. Spectrophotometric method and SQUAD program were applied to extract thermodynamic parameters to explain the complex formation behavior in solution at 25 °C in constant ionic strength (I = 0.1 M NaClO4). Also, density functional theory calculations at different level of DFT and basis set were employed to investigate optimized geometry, vibrational frequency analysis, electronic structure (energy of the HOMO and LUMO, Mulliken atomic charge, dipole moment, hardness and softness, electrophilicity and spectral properties) of the prepared Schiff base compounds. The DFT results showed that proposed structure and stability in ligands and their complexes are in accord with the experimental outcomes.
A new mode of carbene‐catalyzed heteroatom activation and asymmetric reactions is disclosed. The reaction starts with addition of a carbene catalyst to a (benz)imidazole‐derived aldimine substrate. ...Subsequent oxidation and proton transfer lead to the formation of a catalyst‐bound triaza‐diene as the key intermediate, in which the nitrogen atom at a site remote to the catalyst‐substrate bond is activated. This unusual triaza‐diene intermediate then undergoes highly enantioselective reactions with activated ketones through a concerted asynchronous pathway, as supported by mechanistic studies and preliminary density function theory calculation.
A new mode of carbene‐catalyzed activation and reaction of nitrogen atom is disclosed. The reaction starts with the addition of the carbene catalyst to imine to form an aza‐Breslow intermediate to eventually form NHC‐bound triaza‐diene as the key intermediate. This triaza‐diene intermediate then undergoes highly enantioselective reactions with activated ketones through a concerted asynchronous pathway.
Four novel alkaloids of the aaptamine class have been isolated in addition to the known aaptamine, isoaaptamine, demethyl(oxy)aaptamine and its dimethylketal from an unidentified species of ...Indonesian marine sponge of the genus
Xestospongia. Their structures were elucidated on the basis of detailed 1D and 2D NMR spectroscopic data. Their antimicrobial activity was tested towards Gram (+) (
S. aureus), Gram (−) (
E. coli,
V. anguillarum) bacterial strains, a fungus (
C. tropicalis); their cytotoxic activity was evaluated against KB cells.
Four novel alkaloids of the aaptamine class have been isolated from a
Xestospongia sp.
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•Ten inhibitors of the phenyl vinyl sulfone or ethyl acrylate chemotype were prepared.•The potency against four human cathepsins was examined.•The thiol reactivity under physiological ...conditions was estimated.•Compound 6c was identified as a potent cathepsin S inactivator.
A series of inhibitors targeting human cathepsins have been designed and synthesized following a combinatorial approach. The compounds bear an α,β-unsaturated phenyl vinyl sulfone or ethyl acrylate warhead and a peptidomimetic portion aligned to the non-primed binding region. Biochemical evaluation toward four human cathepsins was carried out and the kinetic characterization confirmed an irreversible mode of inhibition. Compound 6c combining the most advantageous building blocks for cathepsin S inhibition was identified as a potent cathepsin S inactivator exhibiting a second-order rate constant of 30600 M−1 s−1.
A series of Pt(0)‐η2‐olefin complexes bearing 1,3,5‐triaza‐7‐phosphaadamantane (PTA) or N‐heterocyclic carbenes are prepared following different synthetic strategies depending on the nature of ...coordinated alkene and spectator ligands. These new platinum(0) derivatives have been tested in vitro as anticancer agents toward three different tumor (human ovarian cancer A2780 and A2780cis and K562 myelogenous leukemia) and one non‐tumor (Hacat keratinocytes) cell lines, proving to be in several cases highly and selectively cytotoxic against ovarian cancer cells. Furthermore, this antiproliferative effect is associated with the activation of an apoptosis process.
In particular, complexes equipped with PTA as spectator ligand give comparable IC50 values on A2780 (cisplatin sensitive) and A2780cis (cisplatin resistant) cell lines, indirectly proving that these new Pt(0) substrates act with a mechanism of action conceivably different from cisplatin. This hypothesis is also confirmed by the fact that our compounds, in contrast to cisplatin, are not able to promote erythroid‐differentiation activity on the K562 myelogenous leukemia cell line.
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In the present paper, we have described the synthesis and biological activity of the novel derivatives of imidazo4,5-
bpyridines and triaza-benzo
cfluorenes (
7–
21,
24–
26,
28–
29). A preponderance ...of these compounds exerted strong cytostatic effects on the panel of seven human tumour cell lines in a dose-dependent manner. In particular, imidazo4,5-
bpyridines and triaza-benzo
cfluorenes including 2-imidazolinyl derivatives showed the most potent antitumour activity. Similarly, triaza-benzo
cfluorenes
18 and
20 induced strong growth inhibition of tested tumour cell lines, and showed low cytotoxicity in normal human fibroblasts. DNA interaction studies of these compounds demonstrated that
N-methylated
16 and 2-imidazolinyl
28 triaza-benzo
cfluorenes bind to DNA in an intercalative mode.
A preponderance of imidazo4,5-
bpyridines exerted strong cytostatic effects in a dose-dependent manner. Derivatives bearing 2-imidazolinyl substituent showed the most potent antitumour activity. DNA interaction studies demonstrated that compounds
16 and
28 bind to DNA in an intercalative mode.
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► Novel imidazo4,5-
bpyridine and triaza-benzo
cfluorene derivatives. ► Strong cytostatic effects on the panel of seven human tumour cell lines in a dose-dependent manner. ► Intercalation into ds DNA in direct relation with concentration depended induction of apoptosis observed in SW620 and MiaPaCa-2 cells. ► High potential of some derivatives as novel leads with anticancer potentials for further
in vivo evaluation.
Cationic 1,3,5‑triaza‑phosphaadamantane (PTA) quinoline ruthenium(II) and iridium(III) complexes were successfully synthesized and characterized using standard spectroscopic and analytical ...techniques. The complexes were evaluated for their in vitro antiplasmodial activities against the chloroquine-sensitive (CQS) NF54 and chloroquine-resistant (CQR) K1 strains of the Plasmodium falciparum species of the malaria parasite and were found to exhibit good activities in the sensitive strain but moderate activities in the resistant strain, suggesting a resistance mechanism similar to chloroquine (CQ). Selected samples were screened for their ability to inhibit synthetic haemozoin formation and were found to be inhibitors with similar activity to CQ. The complexes also exhibit moderate to low cytotoxicity when evaluated against the Chinese Hamster Ovarian (CHO) cell-line in vitro, suggesting selectivity towards the malaria parasite rather than mammalian cells.
Cationic platinum group metal complexes of 7‑chloroquinolines have antiplasmodial activity and are potential haemozoin inhibitors in the malaria parasite. The complexes display selectivity towards the malaria parasite rather than mammalian cells. Display omitted
•Cationic complexes possess antiplasmodial activity against Plasmodium falciparum.•1,3,5‑Triaza‑7‑phosphaadamantane complexes have activity against sensitive strains.•The complexes are potential haemozoin inhibitors in the malaria parasite.•Selectivity towards the malaria parasite rather than mammalian cells
While important efforts were made in the development of positron emission tomography (PET) tracers for the in vivo molecular diagnosis of Alzheimer's disease, very few investigations to develop ...magnetic resonance imaging (MRI) probes were performed. Here, a new generation of Gd(III)-based contrast agents (CAs) is proposed to detect the amyloid β-protein (Aβ) aggregates by MRI, one of the earliest biological hallmarks of the pathology. A building block strategy was used to synthesize a library of 16 CAs to investigate structure–activity relationships (SARs) on physicochemical properties and binding affinity for the Aβ aggregates. Three types of blocks were used to modulate the CA structures: (i) the Gd(III) chelates (Gd(III)-DOTA and Gd(III)-PCTA), (ii) the biovectors (2-arylbenzothiazole, 2-arylbenzoxazole and stilbene derivatives) and (iii) the linkers (neutrals, positives and negatives with several lengths). These investigations revealed unexpected SARs and a difficulty of these probes to cross the blood–brain barrier (BBB). General insights for the development of Gd(III)-based CAs to detect the Aβ aggregates are described.
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•Syntheses of MRI Gd-based contrast agents (CAs) targeted on the Aβ aggregates.•Identification of structural modifications to improve water solubility of the CAs.•Identification of structural modifications to improve amyloid binding of the CAs.•Evaluation of blood–brain barrier crossing of the CAs.•Complete study of a new family of MRI CAs for the diagnosis of Alzheimer's disease.
Activation of the Nociceptin/Orphanin FQ (NOP) receptor may have anti-abuse effects. The present study examined the consequence of NOP receptor activation on the rewarding effect of opiates and ...psychostimulants in the conditioned place preference task in rats. First, the motivational effect of the NOP receptor agonists Ro64-6198 (0.316–3.16
mg/kg i.p.) and Ro65-6570 (1–10
mg/kg i.p.) when administered alone, was assessed. Ro65-6570 was selected for further drug combination studies since, unlike Ro64-6198, it was devoid of an intrinsic motivational effect. Next, the minimal effective dose to induce reward for the opiates heroin (0.1–3.16
mg/kg i.p.), morphine (1–10
mg/kg i.p.), hydrocodone (0.316–10
mg/kg i.p.), tilidine (1–31.6
mg/kg i.p.), hydromorphone (0.1–10
mg/kg i.p.), and oxycodone (0.0316–10
mg/kg i.p.), as well as for the psychostimulants cocaine (3.16–31.6
mg/kg i.p.) and dexamphetamine (0.316–3.16
mg/kg i.p.) in combination with Ro65-6570 (0 or 3.16
mg/kg i.p.) was determined. All drugs produced conditioned place preference, and for opiates and cocaine, but not for dexamphetamine, the minimal effective dose was higher when combined with Ro65-6570 (3.16
mg/kg i.p.). Attenuation of the rewarding effect of tilidine (3.16
mg/kg i.p.) and oxycodone (1
mg/kg i.p.) by Ro65-6570 (3.16
mg/kg i.p.) could be reversed by pre-treatment with the NOP receptor antagonist J-113397 (4.64
mg/kg i.p.), suggesting that the attenuating effect of Ro65-6570 on opiates is due to activation of the NOP receptor. Taken together, the present study suggests that activation of NOP receptors effectively attenuates the rewarding effect of opiates, but may be less effective in reducing psychostimulant-induced reward.
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