RESUMEN

As ribonucleotide reductase (RNR) plays a crucial role in nucleic acid metabolism, it is an important target for anticancer therapy. The thiosemicarbazone Triapine is an efficient R2 inhibitor, which has entered ∼20 clinical trials. Thiosemicarbazones are supposed to exert their biological effects through effectively binding transition-metal ions. In this study, six iminodiacetate-thiosemicarbazones able to form transition-metal complexes, as well as six dicopper(II) complexes, were synthesized and fully characterized by analytical, spectroscopic techniques (IR, UV-vis; 1H and 13C NMR), electrospray ionization mass spectrometry, and X-ray diffraction. The antiproliferative effects were examined in several human cancer and one noncancerous cell lines. Several of the compounds showed high cytotoxicity and marked selectivity for cancer cells. On the basis of this, and on molecular docking calculations one lead dicopper(II) complex and one thiosemicarbazone were chosen for in vitro analysis as potential R2 inhibitors. Their interaction with R2 and effect on the Fe(III)2-Y· cofactor were characterized by microscale thermophoresis, and two spectroscopic techniques, namely, electron paramagnetic resonance and UV-vis spectroscopy. Our findings suggest that several of the synthesized proligands and copper(II) complexes are effective antiproliferative agents in several cancer cell lines, targeting RNR, which deserve further investigation as potential anticancer drugs.

Asunto(s)

Antineoplásicos/farmacología , Inhibidores Enzimáticos/farmacología , Compuestos Organometálicos/farmacología , Ribonucleótido Reductasas/antagonistas & inhibidores , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cobre/química , Cobre/farmacología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Iminoácidos/química , Iminoácidos/farmacología , Ratones , Modelos Moleculares , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Ribonucleótido Reductasas/aislamiento & purificación , Ribonucleótido Reductasas/metabolismo , Relación Estructura-Actividad , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacología , Células Tumorales Cultivadas

RESUMEN

Three ethyl chitosans (ECSs) have been prepared using the ethyl chloride (AA) that was obtained in situ. Each ECS was applied on a 100% cotton fabric through a pad-dry-cure technology. Using the ANOVA as statistic method, the wrinkle-proofing effects have been determined varying the concentrations of AA (0.1-2.1mmol) and chitosan (CS) (0.1-2.1mmol). Alkylation and grafting mechanisms have been confirmed by the results of FTIR, (1)H NMR, XPS, SEM, DSC and termogravimetric analyses. The performances of each ECS as wrinkle-proofing agent have been revealed through quantitative methods (taking-up degree, wrinkle-recovering angle, tensile strength and effect's durability). The ECSs confer wrinkle-recovering angle and tensile strength higher than those of the witness sample. Durability of ECSs grafted on cotton have been demonstrated by a good capacity of dyeing with non-specific (acid/anionic and cationic) dyes under severe working conditions (100°C, 60min) and a good antimicrobial capacity.

Asunto(s)

Quitosano/química , Alquilación , Análisis de Varianza , Celulosa/química , Cloruro de Etilo/química , Espectroscopía Infrarroja por Transformada de Fourier , Resistencia a la Tracción , Termogravimetría

RESUMEN

We report herein a feasible study concerning the design, synthesis, structure and in vitro antimycobacterial and anticancer activity of two new classes (containing four and five fused rings) of indolizine with phenanthroline skeleton. The preparation is straight and efficient, involving a Huisgen [3+2] dipolar cycloaddition of cycloimmonium ylides to alkynes or alkenes dipolarophiles. The cycloaddition reactions are highly stereo- or regioselective, according with the dipolarophiles nature. The structure of the new compounds was assigned unambiguously, X-ray analysis including. The primary antimycobacterial screening reveals that one of the thirteen tested compounds had a good activity against Mycobacterium tuberculosis H37Rv under aerobic conditions. The antiproliferative evaluation against a NCI 60 human tumor cell line panel, revealed that two indolizine with phenanthroline skeleton exhibit a selective and significant antitumor growth inhibitory activity against Breast Cancer (MCF7 and T-47D) and a slightly moderate activity against some forms of Leukemia, Non-Small Cell Lung Cancer, Renal Cancer and Breast Cancer (MDA-MB-468). The X-ray diffraction study of the indolizines with phenanthroline skeleton prove a flat coplanar structure which, corroborated with their anticancer activity, allow us to suggest that an interaction with DNA (via an intercalation mechanism) would be reasonable.

Asunto(s)

Antibacterianos/síntesis química , Antineoplásicos/síntesis química , Indolizinas/síntesis química , Sustancias Intercalantes/síntesis química , Fenantrolinas/síntesis química , Alquenos/química , Alquinos/química , Antibacterianos/farmacología , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Reacción de Cicloadición , Diseño de Fármacos , Humanos , Indolizinas/farmacología , Concentración 50 Inhibidora , Sustancias Intercalantes/farmacología , Pruebas de Sensibilidad Microbiana , Modelos Químicos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/crecimiento & desarrollo , Fenantrolinas/farmacología , Estereoisomerismo

RESUMEN

AIM: To obtain some chalcones and their dibrominated analogues and to evaluate their antimicrobial potential. MATERIAL AND METHODS: Eight chalcones were synthesized using the Claisen-Schmidt condensation of acetophenone/4-bromo-acetophenone and different benzaldehyde derivatives. These chalcones were further brominated using two different bromination agents: molecular bromine and pyridinium tribromide. The antimicrobial activity was tested using the disk diffusion method. RESULTS AND DISCUSSIONS: The classical bromination technique was compared to the eco-friendly one using pyridinium tribromide. Pyridinium tribromide bromination did not improve the reaction yields (except for one compound), but it had the advantage of being a stable, non-corrosive and non-toxic salt. The results of the antimicrobial assessment indicated that the bromination of the double bond slightly increased the antimicrobial potential in some cases, but the results obtained during the antimicrobial evaluation were modest, some of the derivatives being active especially on Sarcina lutea ATCC 9341 and Bacillus cereus ATCC 14579. CONCLUSIONS: In this study, eight chalcones and their dibrominated analogues were synthesized, four of the α,ß-dibromochalcones being reported for the first time. Pyridinium tribromide was used as an alternative for liquid bromine, the main advantage of this method being related to the reduced toxicity of the reagents. The synthesized compounds did not exhibit a very good antimicrobial potential.

Asunto(s)

Antibacterianos/síntesis química , Antibacterianos/farmacología , Bacillus cereus/efectos de los fármacos , Chalconas/síntesis química , Chalconas/farmacología , Sarcina/efectos de los fármacos , Acetofenonas/síntesis química , Acetofenonas/química , Antibacterianos/química , Benzaldehídos/síntesis química , Benzaldehídos/química , Chalconas/química , Pruebas Antimicrobianas de Difusión por Disco , Halogenación , Humanos , Piridinas

RESUMEN

A new diamine, (dimethylsilanediyl)bis(methylene)bis(4-aminobenzoate) (1), containing dimethylsilane spacer, was prepared by the condensation of p-aminobenzoic acid with bis(chloromethyl)dimethylsilane. This was subsequently reacted with salicylaldehyde, 3-hydroxy-salicylaldehyde, and 3-methoxy-salicyladehyde, when corresponding Schiff bases (E)-(dimethylsilanediyl)bis(methylene)bis(4-((E)-(2-hydroxybenzilidene)amino)benzoate (2), (E)-(dimethylsilanediyl)bis(methylene)bis(4-((E)-(2-hydroxybenzilidene)amino)benzoate (3), and (E)-(dimethylsilanediyl)bis(methylene) bis(4-((E)-(2-hydroxy-3-methoxybenzilidene)amino)benzoate (4), respectively were formed. All the obtained compounds were structurally characterized by spectral (FT-IR, (1)HNMR, (13)CNMR) analyses and single crystal X-ray diffraction. Photophysical studies revealed that the new prepared Schiff bases are good UV light absorbing and fluorescent materials. Thus, they exhibit strong UV/Vis-absorption at 250-400nm and violet or orange emission, in sensitive dependence on the polarity of the solvents and the nature of the substituent (H, OH and OCH3) at the aromatic ring. The antimicrobial activity of these compounds was first studied in vitro by the disk diffusion assay against two species of bacteria and three fungi. The minimum inhibitory concentration was then determined with the reference of standard compounds. The results displayed that Schiff bases 3 and 4 having hydroxy- and methoxy-substituents on the aromatic ring were better inhibitors of both types of species (bacteria and fungi) than standard compounds, Caspofungin and Kanamycin.

Asunto(s)

Antiinfecciosos/química , Antiinfecciosos/farmacología , Compuestos Azo/química , Compuestos Azo/farmacología , Compuestos de Organosilicio/química , Compuestos de Organosilicio/farmacología , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacología , Aldehídos/síntesis química , Aldehídos/química , Aldehídos/farmacología , Antiinfecciosos/síntesis química , Compuestos Azo/síntesis química , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Cristalografía por Rayos X , Diaminas/síntesis química , Diaminas/química , Diaminas/farmacología , Hongos/efectos de los fármacos , Humanos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Micosis/tratamiento farmacológico , Compuestos de Organosilicio/síntesis química , Silanos/síntesis química , Silanos/química , Silanos/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Tiosemicarbazonas/síntesis química

RESUMEN

The paper reports the preparation of a poly[2,7-(9,9-dioctylfluorene)-alt-5,5'-bithiophene/PS-ßCD] (PDOF-BTc) polyrotaxane copolymer, through a Suzuki coupling reaction between the 5,5(')-dibromo-2,2'-bithiophene (BT) inclusion complex with persilylated ß-cyclodextrin (PS-ßCD), and 9,9-dioctylfluorene-2,7-bis(trimethylene borate) (DOF) as the blocking group. The chemical structure and the thermal and morphological properties of the resulting polyrotaxane were investigated by using NMR and FT-IR spectroscopy, TGA, DSC and AFM analysis. The encapsulation of BT inside the PS-ßCD cavity results in improvements in the solubility, as well as in different surface morphology and thermal properties of the PDOF-BTc rotaxane copolymer compared to its noncomplexed PDOF-BT homologue. In contrast, the number-average molecular weight (M(n)) of PDOF-BTc rotaxane copolymer indicated lower values suggesting that the condensation reaction is subjected to steric effects of the bulkier silylated groups, affecting the ability of the diborate groups from the DOF molecule to partially penetrate the PS-ßCD cavity.