Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 44
Filter
Add more filters










Type of study
Publication year range
1.
Bioorg Chem ; 95: 103498, 2020 01.
Article in English | MEDLINE | ID: mdl-31855823

ABSTRACT

Two macrocyclic derivatives based on the triclosan frame were designed and synthesized as inhibitors of Mycobacterium tuberculosis InhA enzyme. One of the two molecules M02 displayed promising inhibitory activity against InhA enzyme with an IC50 of 4.7 µM. Molecular docking studies of these two compounds were performed and confirmed that M02 was more efficient as inhibitor of InhA activity. These molecules are the first macrocyclic direct inhibitors of InhA enzyme able to bind into the substrate pocket. Furthermore, these biaryl ether compounds exhibited antitubercular activities comparable to that of triclosan against M. tuberculosis H37Rv strain.


Subject(s)
Antitubercular Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Macrocyclic Compounds/pharmacology , Mycobacterium tuberculosis/drug effects , Oxidoreductases/antagonists & inhibitors , Triclosan/pharmacology , Antitubercular Agents/chemical synthesis , Antitubercular Agents/chemistry , Bacterial Proteins/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Macrocyclic Compounds/chemical synthesis , Macrocyclic Compounds/chemistry , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Structure , Mycobacterium tuberculosis/enzymology , Oxidoreductases/metabolism , Structure-Activity Relationship , Triclosan/chemical synthesis , Triclosan/chemistry
2.
J Nat Prod ; 82(12): 3233-3241, 2019 12 27.
Article in English | MEDLINE | ID: mdl-31800248

ABSTRACT

Six new secocycloartane glycosides (1-6) were isolated from the ethanol extract of the flowers of Cordia lutea Lam. on the basis of bioassay-guided fractionation. Their structures were determined by the application of NMR and MS data analyses together with X-ray crystallographic analyses for compounds 1 and 2. Compounds 1-6 represent the first examples of 9,10-seco-29-norcycloartane glycosides. These compounds showed significant in vitro anti-Helicobacter pylori activity, and no activity against either Escherichia coli or Pseudomonas aeruginosa. Significant activity was observed for 5 and 6 against Staphylococcus aureus. All compounds displayed weak cytotoxicity against RAW 264.7 cells. The in vitro antileishmanial and antiplasmodial activities of 1-6 were also evaluated.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Cordia/chemistry , Flowers/chemistry , Glycosides/chemistry , Glycosides/pharmacology , Plants, Medicinal/chemistry , Animals , Anti-Bacterial Agents/isolation & purification , Antiprotozoal Agents/isolation & purification , Crystallography, X-Ray , Glycosides/isolation & purification , Mice , Microbial Sensitivity Tests , Molecular Structure , Plasmodium falciparum/drug effects , RAW 264.7 Cells , Spectrum Analysis/methods
3.
J Enzyme Inhib Med Chem ; 34(1): 773-782, 2019 Dec.
Article in English | MEDLINE | ID: mdl-30843736

ABSTRACT

In this work, two bidentate 2-pyridyl-1,2,3-triazole ligands (3a and 3b) containing a 4-substituted benzenesulfonamide pharmacophore prepared by classical click chemistry procedures, as well as their corresponding rhenium complexes, 4a and 4b of general formula [ReCl(CO)3(L)] (L = 3a or 3b) were prepared and fully characterised by spectroscopic methods (IR, NMR, MS, UV-Vis), elemental analysis, X-ray diffraction, and theoretical studies using DFT and TD-DFT methods. In particular, we showed that, in the solid state, the pyridine and the triazole rings of 3b adopted an uncommon cis configuration which stems from intermolecular hydrogen bonds. Preliminary assays demonstrated a promising nanomolar inhibitory activity against carbonic anhydrase isoform IX for both ligands and complexes with a strong affinity Ki of 2.8 nM for ligand 3a. More interestingly, complex 4b exhibited a pronounced selectivity against hCA IX over the off-targets hCA I and hCA II which makes this compound a promising potential anticancer drug candidate.


Subject(s)
Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase IX/antagonists & inhibitors , Carbonic Anhydrase I/antagonists & inhibitors , Carbonic Anhydrase Inhibitors/pharmacology , Density Functional Theory , Antigens, Neoplasm/metabolism , Carbon Monoxide/chemistry , Carbon Monoxide/pharmacology , Carbonic Anhydrase I/metabolism , Carbonic Anhydrase II/metabolism , Carbonic Anhydrase IX/metabolism , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Crystallography, X-Ray , Dose-Response Relationship, Drug , Humans , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Models, Molecular , Molecular Structure , Rhenium/chemistry , Rhenium/pharmacology , Structure-Activity Relationship , Sulfonamides/chemistry , Sulfonamides/pharmacology , Triazoles/chemistry , Triazoles/pharmacology , Benzenesulfonamides
4.
Small ; 12(47): 6602-6612, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27977082

ABSTRACT

Six conjugates of benzoxazole and green fluorescent protein chromophore that differ by the length of their alkyl chain (from C1 to C16) are investigated. They exhibit rigidofluorochromism and clear aggregation-induced emission enhancement (AIEE) behavior with emission in the orange-red that is specific to the solid state. A preparation method based on solvent exchange is used to prepare particles. The self-association properties of these molecules depend on the length of the alkyl chain. Microfibers, platelets, and rounded microparticles are successively obtained by increasing the chain length. The same method is used to prepare nanoparticles (NPs) that are fully characterized. In particular, homogeneous populations of stable NPs measuring around 70 nm are obtained with the analogs whose chains contain four to eight carbon atoms. The behavior with respect to living cells is also influenced by the nature of the compounds. Only the dyes with intermediate hydrophobicity are efficiently uptaken by both normal and tumor cells, and fluorescence only originates from dispersed dye molecules. There is no evidence for incorporation of NPs into cells. This work shows that small variations of the chemical structure must be taken into account for making the best use of AIEE compounds in view of precise applications.


Subject(s)
Benzoxazoles/chemistry , Green Fluorescent Proteins/chemistry , Nanoparticles/chemistry , Fluorescent Dyes/chemistry , Microscopy, Electrochemical, Scanning , Nanoparticles/ultrastructure
5.
Phys Chem Chem Phys ; 18(43): 29999-30008, 2016 Nov 21.
Article in English | MEDLINE | ID: mdl-27774564

ABSTRACT

The arrangement of an ionic fluorophore in the crystalline state was regulated by the presence of various counter-ions and the effect on spectroscopic and self-association properties was studied. To do so, nine salts of berberine (i.e. a fluorescent natural alkaloid) were investigated. Most of them contained organic anions and were prepared using an ion-exchange process. Berberine chloride and hemisulfate were also used for the sake of comparison. The diffuse reflectance and photoluminescence spectra were recorded on powder compounds. All salts were emissive in the solid state and the emission efficiency was increased seven-fold with the nature of the anion. The optical properties were tentatively discussed on the basis of the crystal-packing mode. The possibility of implementing a bottom-up approach to generate microparticles was investigated using the reprecipitation method. Salts that contain the most hydrophobic anions gave a large number of homogeneous, elongated microparticles. This study showed that most of the berberine salts could be used as fluorescent materials, but proper choice of the anion allows using the self-association properties to best advantage.

6.
Eur J Med Chem ; 70: 37-48, 2013.
Article in English | MEDLINE | ID: mdl-24140915

ABSTRACT

We report here the discovery, synthesis and screening results of a series of 3-(9H-fluoren-9-yl)pyrrolidine-2,5-dione derivatives as a novel class of potent inhibitors of Mycobacterium tuberculosis H37Rv strain as well as the enoyl acyl carrier protein reductase (ENR) InhA. Among them, several compounds displayed good activities against InhA which is one of the key enzymes involved in the type II fatty acid biosynthesis pathway of the mycobacteria cell wall. Furthermore, some exhibited promising activities against M. tuberculosis and multi-drug resistant M. tuberculosis strains.


Subject(s)
Antitubercular Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Drug Design , Enzyme Inhibitors/pharmacology , Mycobacterium tuberculosis/drug effects , Oxidoreductases/antagonists & inhibitors , Pyrrolidinones/pharmacology , Antitubercular Agents/chemical synthesis , Antitubercular Agents/chemistry , Bacterial Proteins/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Kinetics , Microbial Sensitivity Tests , Models, Molecular , Molecular Structure , Mycobacterium tuberculosis/enzymology , Mycobacterium tuberculosis/growth & development , Oxidoreductases/metabolism , Pyrrolidinones/chemical synthesis , Pyrrolidinones/chemistry , Structure-Activity Relationship
7.
Eur J Med Chem ; 69: 167-73, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24016834

ABSTRACT

Two series of α-ketotriazole and α,ß-diketotriazole derivatives were synthesized and evaluated for antitubercular and cytotoxic activities. Among them, two α,ß-diketotriazole compounds, 6b and 9b, exhibited good activities (minimum inhibitory concentration = 7.6 µM and 6.9 µM, respectively) on Mycobacterium tuberculosis and multi-drug resistant M. tuberculosis strains and presented no cytotoxicity (IC50 > 50 µM) on colorectal cancer HCT116 and normal fibroblast GM637H cell lines. These two compounds represent promising leads for further optimization.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Ketones/pharmacology , Mycobacterium tuberculosis/drug effects , Triazoles/pharmacology , Anti-Bacterial Agents/chemistry , Dose-Response Relationship, Drug , HCT116 Cells , Humans , Ketones/chemical synthesis , Ketones/chemistry , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium tuberculosis/growth & development , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistry
8.
Dalton Trans ; 42(19): 7019-31, 2013 May 21.
Article in English | MEDLINE | ID: mdl-23515521

ABSTRACT

Three new pyridyltriazole ligands (named pyta) bearing a 4-substituted phenyl arm (nitro- (2a), chloro- (2b) or aminophenyl (2c) moiety) have been synthesized using a convenient click chemistry strategy. The corresponding tricarbonylrhenium complexes 3a, 3b and 3c were prepared and fully characterized by means of NMR, IR and mass spectrometry, as well as X-ray crystallography for two of them (3a and 3b). The direct connection of a 4-substituted phenyl arm at the N1 position of the triazolyl ring has a significant influence on the geometry of both, the ligands and their corresponding Re-complexes. The dominant structural feature of these complexes concerns the crystal cohesion. Slip-stacked π-π interactions between two molecules of the complex were observed for 3a and 3b probably resulting from the co-planarity of the organic framework. Furthermore, a combined experimental study and DFT calculations showed that the nature of the pendant arm (X = NO2, NH2 or Cl) could affect the electronic properties of the Re-complexes. If the chloro- or aminophenyl moieties unmodified the photo-physical properties of the complexes 3b and 3c, the presence of a nitrophenyl arm for the complex 3a quenched the luminescence, due to a high probability of non-radiative deactivation.


Subject(s)
Coordination Complexes/chemistry , Rhenium/chemistry , Triazoles/chemistry , Coordination Complexes/chemical synthesis , Crystallography, X-Ray , Ligands , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Quantum Theory
9.
Dalton Trans ; 42(4): 1136-43, 2013 Jan 28.
Article in English | MEDLINE | ID: mdl-23171922

ABSTRACT

N-Phenylsuccinimides and the corresponding pyrrolidines containing 9,10-dihydroanthracenyl skeletons were used for exploring their ability to coordinate RuCp(+) moieties through the aromatic rings. Electronic and steric tuning of ligands led to mono-, bi- and tri-metallic complexes. A full structural study was carried out in order to characterize the ruthenium organometallic compounds, proving the different coordination modes both in solution (NMR) and in solid state (X-ray diffraction). A modelling study (at DFT level) was completed with the aim to understand the selective π-coordination observed for mono- and bi-metallic complexes.

10.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 10): m1313-4, 2012 Oct 01.
Article in English | MEDLINE | ID: mdl-23125624

ABSTRACT

In the title compound, [Ru(3)(C(25)H(23)N)(C(5)H(5))(3)]·3PF(6)·2C(3)H(6)O], the cation is a triruthenium complex of a 9,10-dihydro-anthracene derivative. Three RuCp(+) (Cp is cyclo-penta-dien-yl) groups are bonded to the three aromatic rings of the ligand. Surprisingly, the pyramidalized N atom of the heterocycle (Σ C-N-C = 329.0°) points towards the anthracenyl group, so losing its coordinative ability. There is an inter-molecular C-H⋯π inter-action involving an acetone mol-ecule and the adjacent benzyl ring of the ligand. In the crystal, mol-ecules are linked via a number of C-H⋯O and C-H⋯F inter-actions and a C-H⋯π inter-action, leading to the formation of a three-dimensional supra-molecular structure. One of the Cp groups is disordered over two positions, with refined occupancies of 0.695 (14):0.305 (14). Two of the three hexa-fluoro-phospate anions are disordered, with refined occupancies of 0.630 (6):0.370 (6) and 0.771 (8):0.229 (8). One of the two solvent acetone mol-ecules is also disordered, with refined occupancies of 0.82 (2):0.18 (2).

11.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 10): o2881, 2012 Oct 01.
Article in English | MEDLINE | ID: mdl-23125679

ABSTRACT

In the title compound, C(25)H(23)N·CHCl(3), the dihydro-anthracene unit is bent with a dihedral angle between the benzene rings of 57.82 (8)°. The N atom of the pyrrolidine heterocycle, which has an envelope conformation with the N atom as the flap, exhibits a pronounced pyramidalization [Σ(C-N-C) = 328.07°], indicating an accentuated N-donor character. In the crystal, this behaviour is evident by the C-H⋯N hydrogen bond involving a solvent mol-ecule and the N atom. The absolute configuration at the C-atom fused positions of the pyrrolidine group were crystallographically confirmed to be S and R.

12.
Inorg Chem ; 51(21): 11716-21, 2012 Nov 05.
Article in English | MEDLINE | ID: mdl-23088415

ABSTRACT

The first monogermylenerhodium complexes stabilized by bulky amidinato ligands on the divalent germanium center have been synthesized and characterized by NMR spectroscopy and X-ray crystallography. Their stability strongly depends on the steric hindrance of the amidinato ligand. With trimethysilyl groups on the nitrogen atoms of the amidinato ligand, only the germylene oxide rhodium complex could be obtained; by contrast, with t-Bu groups, the germylenerhodium complex was isolated. In both cases, the formation of amidinatorhodium complexes was observed. The donating ability of the germylene ligand has been assessed from the CO stretching frequency of the corresponding dicarbonylrhodium complex and was confirmed by density functional theory calculations.

13.
Inorg Chem ; 51(14): 7782-7, 2012 Jul 16.
Article in English | MEDLINE | ID: mdl-22747413

ABSTRACT

The first diphosphaalkenylstannylene stabilized through complexation with a carbene NHC-Sn[C(Cl)═PMes*](2)1 (Mes* = 2,4,6-tri-tert-butylphenyl; NHC = :C{N(iPr)C(Me)}(2)) was isolated and fully characterized including single crystal X-ray diffraction analysis. Its reaction with elemental sulfur rapidly gives the cyclic Sn(2)S(2) (dithiadistannetanne) derivative 3, presumably formed by dimerization of a stannathione intermediate. By contrast, its germanium analogue NHC-Ge[C(Cl)═PMes*](2)7 leads to the corresponding monomeric germathione 4 and germaselenone 5. The germaselenone was more stable than the germathione and could be structurally characterized. An unusual thermal cyclization reaction of the last one occurs with an excess of selenium to give the Ge(2)Se(3) (triselenadigermolane) ring derivative 6.

14.
Chem Commun (Camb) ; 48(30): 3629-31, 2012 Apr 14.
Article in English | MEDLINE | ID: mdl-22392095

ABSTRACT

The new bis(phosphaalkenyl) germanium(II) compound (NHC)Ge(CCl=PMes*)(2) reacts with L(2)M(CO)(4) (M = Mo, W) to give bidentate complexes with an unexpected coordinating behaviour involving the Ge(II) centre and one phosphorus atom, and with AuI or Me(2)SAuCl to afford the monodentate complexes coordinated at the germanium(II) atom.

15.
J Lipid Res ; 53(4): 718-25, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22285872

ABSTRACT

We recently established that drugs used for the treatment and the prophylaxis of breast cancers, such as tamoxifen, were potent inhibitors of cholesterol-5,6-epoxide hydrolase (ChEH), which led to the accumulation of 5,6α-epoxy-cholesterol (5,6α-EC) and 5,6ß-epoxy-cholesterol (5,6ß-EC). This could be considered a paradox because epoxides are known as alkylating agents with putative carcinogenic properties. We report here that, as opposed to the carcinogen styrene-oxide, neither of the ECs reacted spontaneously with nucleophiles. Under catalytic conditions, 5,6ß-EC remains unreactive whereas 5,6α-EC gives cholestan-3ß,5α-diol-6ß-substituted compounds. These data showed that 5,6-ECs are stable epoxides and unreactive toward nucleophiles in the absence of a catalyst, which contrasts with the well-known reactivity of aromatic and aliphatic epoxides. These data rule out 5,6-EC acting as spontaneous alkylating agents. In addition, these data support the existence of a stereoselective metabolism of 5,6α-EC.


Subject(s)
Cholesterol/analogs & derivatives , Epoxy Compounds/chemistry , Alkylation , Catalysis , Cholesterol/chemistry , Crystallography, X-Ray , Culture Media/chemistry , Ethanolamine/chemistry , Guanine/chemistry , Mercaptoethanol/chemistry , Models, Molecular , Stereoisomerism
16.
Langmuir ; 28(1): 855-63, 2012 Jan 10.
Article in English | MEDLINE | ID: mdl-22128833

ABSTRACT

2-Phenyl-benzoxazole and five derivatives bearing an alkyl or alkoxy substituent on the phenyl ring were used to prepare aqueous suspensions of particles via a solvent-exchange method. In these conditions, the methyl and methoxy derivatives spontaneously gave nanofibers, while the other compounds led to microcrystals. This shows that minor chemical changes are enough to direct the formation of a given type of particle. From a spectroscopic viewpoint, all compounds strongly emit blue light in the solid state, with spectra much broader than those registered in n-heptane and ethanol solutions. The photoluminescence quantum yields reached 38% and were slightly affected in aqueous suspension by the polarity of the environment. The molecular arrangement, deduced from X-ray analysis for the methyl and methoxy derivatives, was used to explain the fluorescence properties in the solid state. This work shows that 2-phenyl-benzoxazole derivatives are interesting candidates for applications as fluorescent nanomaterials, including in aqueous and biological media.


Subject(s)
Benzoxazoles/chemistry , Fluorescent Dyes/chemistry , Nanofibers , Crystallization , Crystallography, X-Ray
17.
Org Biomol Chem ; 9(23): 8163-70, 2011 Dec 07.
Article in English | MEDLINE | ID: mdl-21986639

ABSTRACT

New phytosphingosine analogues have been conceived, synthesised and their cytotoxicity in B16 murine melanoma cells tested. These compounds embed an isomeric substitution pattern resulting from a formal permutation of the C-2 and C-4 substituents along the aliphatic skeleton of the original sphingoid base. Five different stereoisomers have been accessed through regio- and stereocontrolled opening of the oxirane of long chain epoxyamine precursors. The corresponding N-hexyl and N-octanoyl derivatives have also been prepared. In cell viability experiments all the primary amines were found to be more active than the natural phytosphingosine with IC(50) in the low µM range for the most potent compounds.


Subject(s)
Sphingosine/analogs & derivatives , Animals , Cell Line, Tumor , Cell Survival/drug effects , Hydrolysis , Mice , Models, Molecular , Molecular Structure , Sphingosine/chemical synthesis , Sphingosine/pharmacology , Stereoisomerism
18.
Chemistry ; 17(45): 12763-72, 2011 Nov 04.
Article in English | MEDLINE | ID: mdl-21956731

ABSTRACT

Phosphagermaallene Tip(tBu)Ge=C=PMes* 1 (Tip=2,4,6-triisopropylphenyl, Mes*=2,4,6-tri-tert-butylphenyl) reacts with phenyl isocyanate and tert-butyl isocyanate by a [2+2] cycloaddition that involves the Ge=C and C=O double bonds to afford 1-oxa-2-germacyclobutanes 2 and 3. With N,N'-dicyclohexylcarbodiimide, a [2+2] cycloaddition is observed between the Ge=C and C=N unsaturations to lead to 1-aza-2-germacyclobutane 6 with exocyclic P=C and C=N double bonds. In sharp contrast, 1 reacts with phenyl isothiocyanate, ethyl isothiocyanate, and carbon disulfide according to a [3+2] cycloaddition that involves the whole Ge=C=P unit and the C=S double bond to give transient phosphagermacarbenes (PGeHCs) 11, 12, and 13. These new PGeHCs undergo C-H insertions into one o-tBu group of Mes* (in the case of 11 and 12) or one o-iPr group of Tip (in the case of 13) with formation of tricyclic compounds 8, 9, and 10, respectively. The reaction mechanisms that involve 1 and the phenyl isocyanate and the phenyl isothiocyanate are described and their regioselectivity is explained by theoretical calculations.

20.
Chem Commun (Camb) ; 47(28): 8163-5, 2011 Jul 28.
Article in English | MEDLINE | ID: mdl-21691641

ABSTRACT

ortho-(Dimesitylboryl)phenylphosphines 1 and 2 were applied in Pd-catalyzed Suzuki-Miyaura C-C couplings. Coordination studies were performed in order to rationalize the relationship between structure and reactivity. Full characterization of a Pd(0) complex derived from 1 has evidenced a new coordination mode for phosphine-arylboranes involving secondary π-interaction between one of the mesityl groups at boron and the metal centre.

SELECTION OF CITATIONS
SEARCH DETAIL
...