RESUMEN

Herein, a novel fluorescent probe RhoDCM was developed for monitoring the cysteine (Cys) dynamics. For the first time, the Cys-triggered implement was applied in relatively complete diabetic mice models. The response of RhoDCM towards Cys suggested advantages including practical sensitivity, high selectivity, rapid reaction, and steadiness in various pH and temperature conditions. RhoDCM could basically monitor the intracellular Cys level, both exogenous and endogenous. It could further monitor the glucose level via detecting consumed Cys. Furthermore, the diabetic mice models including the no diabetic control group, the induced model groups by streptozocin (STZ) or alloxan, and the treatment groups induced by STZ and treated with vildagliptin (Vil), dapagliflozin (DA), or metformin (Metf) were constructed. The models were checked by oral glucose tolerance test and significant liver-related serum indexes. Based on the models, the in vivo imaging and penetrating depth fluorescence imaging both indicated that RhoDCM could characterize the status of the development and treatment in the diabetic process via monitoring the Cys dynamics. Consequently, RhoDCM seemed beneficial for inferring the order of severity in the diabetic process and evaluating the potency of therapeutic schedules, which might be informatic for correlated investigations.

Asunto(s)

Diabetes Mellitus Experimental , Metformina , Ratones , Animales , Humanos , Cisteína/química , Diabetes Mellitus Experimental/diagnóstico por imagen , Diabetes Mellitus Experimental/tratamiento farmacológico , Colorantes Fluorescentes/química , Metformina/farmacología , Metformina/uso terapéutico , Imagen Óptica , Células HeLa

RESUMEN

Major depressive disorder (MDD) is one of the most common mental disorders. We designed a fast-onset antidepressant that works by disrupting the interaction between the serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN). Chronic unpredictable mild stress (CMS) selectively increased the SERT-nNOS complex in the DRN in mice. Augmentation of SERT-nNOS interactions in the DRN caused a depression-like phenotype and accounted for the CMS-induced depressive behaviors. Disrupting the SERT-nNOS interaction produced a fast-onset antidepressant effect by enhancing serotonin signaling in forebrain circuits. We discovered a small-molecule compound, ZZL-7, that elicited an antidepressant effect 2 hours after treatment without undesirable side effects. This compound, or analogous reagents, may serve as a new, rapidly acting treatment for MDD.

Asunto(s)

Antidepresivos , Trastorno Depresivo Mayor , Núcleo Dorsal del Rafe , Diseño de Fármacos , Óxido Nítrico Sintasa de Tipo I , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Animales , Ratones , Antidepresivos/química , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Núcleo Dorsal del Rafe/efectos de los fármacos , Núcleo Dorsal del Rafe/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo

RESUMEN

BACKGROUND: The aim of this study is to compare double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) and indirect ELISA in the diagnosis of hepatitis C virus（HCV）infection. METHODS AND MATERIALS: A total of 176 samples from the Tumor Hospital Affiliated to Xin Jiang Medical University were utilized to comparison. All serum samples were tested using double-antigen sandwich ELISA and indirect ELISA. Cohen's kappa statistics were used to assess the agreement between the two assays, and multivariate analysis was used to evaluate risk factors for the discordance between the double-antigen ELISA and indirect ELISA. RESULTS: The positivities of indirect ELISA (Beijing Wantai), double-antigen sandwich ELISA (Beijing Wantai), and indirect ELISA (Beijing Jinhao) were 74.43%, 68.75%, and 73.30%, respectively. The agreement between the indirect ELISA (Beijing Wantai) and double-antigen sandwich ELISA (Beijing Wantai) was high (κ = 0.829;P < .001), and the agreement between the double-antigen sandwich ELISA (Beijing Wantai) and indirect ELISA (Beijing Jinhao) was high (κ = 0.847;P < .001). Variables associated with discordant results between the double-antigen sandwich and indirect ELISA in multivariate analysis were as follows: female (OR:1.462; P < .05), age (<35 years old; OR:3.667; P < .05), and cancer (suffer from malignant tumor; OR:3.621; P < .05). CONCLUSION: In detection of HCV, high agreement was found between the double-antigen sandwich ELISA and indirect ELISA. Female, younger age, and suffer from malignant tumor were significant risk factors for the discordance. Based on double-antigen sandwich ELISA has distinct methodological advantages over indirect ELISA. It is recommended for the diagnosis of HCV infection.

Asunto(s)

Ensayo de Inmunoadsorción Enzimática , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/diagnóstico , Pruebas Inmunológicas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos Virales/metabolismo , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/normas , Femenino , Hepacivirus/inmunología , Hepatitis C/inmunología , Anticuerpos contra la Hepatitis C/metabolismo , Humanos , Pruebas Inmunológicas/métodos , Pruebas Inmunológicas/normas , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto Joven

RESUMEN

A practical strategy of introducing ortho-methoxyl group was explored to achieve the fluorescence-enhancing and bathochromic-shift bi-functional optimization. It was tested in the Cys sensing ISOPH-X series, thus the successful case, ISOPH-2, was obtained. It realized the optimization in a simple and compatible way. The corresponding strategy was basically established during the confirmation of checkpoints including applicable steadiness (over 24 h), wide pH range (7.0-9.0), rapid response (20 min), good biocompatibility, high sensitivity (LOD = 0.072 nm), high selectivity and biological monitoring of Cys in living cells as well as C. elegans. In this work, the o-methoxyl introduction strategy led to a 15 nm red shift and a near 4-fold fluorescence enhancement. This strategy could be combined with the double bond-introducing approach. Compared with reported strategies, by breaking the dilemma between red shift and strong fluorescent intensity, this strategy might offer beneficial information for exploiting better sensors with more fluorophores and mechanisms for their targets.

RESUMEN

Potassium (K+ ) is an essential macronutrient for plant growth and development. Transporters from the KT/HAK/KUP family play crucial roles in K+ homeostasis and cell growth in various plant species. However, their physiological roles in maize are still unknown. In this study, we cloned ZmHAK5 and ZmHAK1 and investigated their functions in maize (Zea mays L.). In situ hybridization showed that ZmHAK5 was mainly expressed in roots, especially in the epidermis, cortex, and vascular bundle. ZmHAK5 was characterized as a high-affinity K+ transporter. Loss of function of ZmHAK5 led to defective K+ uptake in maize, under low K+ conditions, whereas ZmHAK5-overexpressing plants showed increased K+ uptake activity and improved growth. ZmHAK1 was upregulated under low K+ stress, as revealed by RT-qPCR. ZmHAK1 mediated K+ uptake when heterologously expressed in yeast, but its transport activity was weaker than that of ZmHAK5. Overexpression of ZmHAK1 in maize significantly affected K+ distribution in shoots, leading to chlorosis in older leaves. These findings indicate that ZmHAK5 and ZmHAK1 play distinct roles in K+ homeostasis in maize, functioning in K+ uptake and K+ distribution, respectively. Genetic manipulation of ZmHAK5 may represent a feasible way to improve K+ utilization efficiency in maize.

Asunto(s)

Proteínas de Plantas/metabolismo , Potasio/metabolismo , Potasio/farmacología , Zea mays/metabolismo , Arabidopsis/genética , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Mutación/genética , Fenotipo , Proteínas de Plantas/genética , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Plantas Modificadas Genéticamente , ARN Mensajero/genética , ARN Mensajero/metabolismo , Saccharomyces cerevisiae/metabolismo , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Nicotiana/metabolismo , Zea mays/efectos de los fármacos , Zea mays/genética

RESUMEN

In the present work, twenty-five nicotinoyl pyrazoline derivates bearing N-methyl indole moiety have been designed and synthesized. The biological evaluation of these compounds as tubulin assembly inhibitors revealed that most of them were potential antitumor agents. Among them, compound 28 exhibited most potency against cancer cell line panels (GI50 = 29-90 nM for HeLa, HepG2 and MCF-7 cells) without toxicity to non-tumor cells (CC50 > 300 µM for 293 T cell), bound to the colchicine site of tubulin and displayed excellent inhibitory activity in tubulin assembly assay (IC50 = 1.6 µM, better than CA-4). Molecular dynamics simulation was carried out to validate the docking pose of compound 28 with tubulin crystalline. Further investigation on HepG2 and HeLa cells demonstrated that compound 28 could cause mitosis arrest to G2/M phase, and subsequently induced cell apoptosis. The efficiency in vivo of compound 28 was also evaluated on HeLa-Xenograft nude mice, and the relative tumor inhibition ration was up to 61.52% without noticeable weight loss and tissue damage (examined by H&E staining), which was comparable to CA-4 (inhibited 59.92%). In brief, compound 28 is a promising candidate for tumor therapy as tubulin assembly inhibitor.

Asunto(s)

Antineoplásicos/química , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Pirazoles/química , Pirazoles/uso terapéutico , Moduladores de Tubulina/química , Moduladores de Tubulina/uso terapéutico , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Diseño de Fármacos , Femenino , Células HEK293 , Células HeLa , Humanos , Indoles/química , Indoles/farmacología , Indoles/uso terapéutico , Ratones Desnudos , Mitosis/efectos de los fármacos , Modelos Moleculares , Neoplasias/metabolismo , Neoplasias/patología , Pirazoles/farmacología , Moduladores de Tubulina/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología

RESUMEN

A series of 1-methyl-1H-indole-pyrazoline hybrids were designed, synthesized, and biologically evaluated as potential tubulin polymerization inhibitors. Among them, compound e19 [5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide] showed the most potent inhibitory effect on tubulin assembly (IC50 =2.12 µm) and in vitro growth inhibitory activity against a panel of four human cancer cell lines (IC50 values of 0.21-0.31 µm). Further studies confirmed that compound e19 can induce HeLa cell apoptosis, cause cell-cycle arrest in G2 /M phase, and disrupt the cellular microtubule network. These studies, along with molecular docking and 3D-QSAR modeling, provide an important basis for further optimization of compound e19 as a potential anticancer agent.

Asunto(s)

Antineoplásicos/farmacología , Indoles/farmacología , Pirazoles/farmacología , Moduladores de Tubulina/farmacología , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Sitios de Unión , Línea Celular Tumoral , Puntos de Control de la Fase G2 del Ciclo Celular , Humanos , Indoles/síntesis química , Simulación del Acoplamiento Molecular , Pirazoles/síntesis química , Relación Estructura-Actividad Cuantitativa , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntesis química

RESUMEN

A series of 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole derivatives were designed, synthesized and evaluated as potential tubulin polymerization inhibitors and for the cytotoxicity against anthropic cancer cell lines. Among the novel compounds, compound 11f was demonstrated the most potent tubulin polymerization inhibitory activity (IC50 = 1.5 µM) and antiproliferative activity against A549, HepG2 and MCF-7 (GI50 = 2.4, 3.8 and 5.1 µM, respectively), which was compared with the positive control colchicine and CA-4. We also evaluated that compound 11f could effectively induce apoptosis of A549 associated with G2/M phase cell cycle arrest. Docking simulation and 3D-QSAR model in these studies provided more information that could be applied to design new molecules with more potent tubulin inhibitory activity.

Asunto(s)

Benceno/síntesis química , Benceno/farmacología , Bencimidazoles/síntesis química , Bencimidazoles/farmacología , Diseño de Fármacos , Indoles/síntesis química , Indoles/farmacología , Simulación del Acoplamiento Molecular , Multimerización de Proteína/efectos de los fármacos , Tubulina (Proteína)/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Benceno/química , Benceno/metabolismo , Bencimidazoles/química , Bencimidazoles/metabolismo , División Celular/efectos de los fármacos , Línea Celular Tumoral , Técnicas de Química Sintética , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Indoles/química , Indoles/metabolismo , Estructura Cuaternaria de Proteína , Relación Estructura-Actividad Cuantitativa , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química , Moduladores de Tubulina/metabolismo , Moduladores de Tubulina/farmacología

RESUMEN

A series of novel pyrazoline-containing derivatives (15-47) has been designed, synthesized and evaluated for their biological activities. Among them, compound 18 displayed the most potent antiproliferative activity against A549, MCF-7 and HepG-2 cells line (IC50 = 0.07 µM, 0.05 µM, 0.03 µM, respectively) and the tubulin polymerization inhibitory activity (IC50 = 1.88 µM), being comparable to CA-4. Furthermore, we also tested that compound 18 was a potent inducer of apoptosis in HepG-2 cells and it had cellular effects typical for microtubule interacting agents, causing accumulation of cells in the G2/M phase of the cell cycle. These studies, along with molecular docking, provided a new molecular scaffold for the further development of antitumor agents that target tubulin.

Asunto(s)

Antineoplásicos/farmacología , Diseño de Fármacos , Pirazoles/farmacología , Moduladores de Tubulina/farmacología , Tubulina (Proteína)/metabolismo , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Células MCF-7 , Simulación del Acoplamiento Molecular , Estructura Molecular , Pirazoles/síntesis química , Pirazoles/química , Relación Estructura-Actividad , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química

RESUMEN

Interference with dynamic equilibrium of microtubule-tubulin has proven to be a useful tactics in the clinic. Based on investigation into the structure-activity relationship (SAR) studies of tubulin polymerization inhibitors obtained from several worldwide groups, we attempted to design 691 compounds covering several main heterocyclic scaffolds as novel colchicine-site inhibitors (CSIs). Evaluated by a series of combination of commonly used computer methods such as molecular docking, 3D-QSAR, and pharmacophore model, we can obtain the ultimate 16 target compounds derived from five important basic scaffolds in the field of medicinal chemistry. Among these compounds, compound A-132 with in silico moderate activity was synthesized, and subsequently validated for preliminary inhibition of tubulin polymerization by immunofluorescence assay. In additional, the work of synthesis and validation of biological activity for other 15 various structure compounds will be completed in our laboratory. This study not only developed a hierarchical strategy to screen novel tubulin inhibitors effectively, but also widened the spectrum of chemical structures of canonical CSIs.

Asunto(s)

Colchicina/metabolismo , Relación Estructura-Actividad Cuantitativa , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacología , Sitios de Unión , Proliferación Celular/efectos de los fármacos , Técnicas de Química Sintética , Evaluación Preclínica de Medicamentos/métodos , Células Hep G2/efectos de los fármacos , Humanos , Simulación del Acoplamiento Molecular , Reproducibilidad de los Resultados , Moduladores de Tubulina/síntesis química

RESUMEN

A series of metronidazole-thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, 1H NMR and MS. They were also tested for antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5e exhibited the most potent inhibitory activity against E. coli FabH with IC50 of 4.9µM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5a, 5b, 5d, 5e, 5g and 5i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability.

RESUMEN

A series of 1,3,4-thiadiazol-2-amide derivatives (6a-w) were designed and synthesized as potential inhibitors of tubulin polymerization and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 6f exhibited the most potent anticancer activity against A549, MCF-7 and HepG2 cancer cell lines with IC50 values of 0.03 µM, 0.06 µM and 0.05 µM, respectively. Compound 6f also exhibited significant tubulin polymerization inhibitory activity (IC50=1.73 µM), which was superior to the positive control. The obtained results, along with a 3D-QSAR study and molecular docking that were used for investigating the probable binding mode, could provide an important basis for further optimization of compound 6f as a novel anticancer agent.

Asunto(s)

Amidas/química , Amidas/farmacología , Antineoplásicos/síntesis química , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/farmacología , Amidas/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Sitios de Unión , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Células Hep G2 , Humanos , Puntos de Control de la Fase M del Ciclo Celular/efectos de los fármacos , Células MCF-7 , Conformación Molecular , Simulación del Acoplamiento Molecular , Estructura Terciaria de Proteína , Relación Estructura-Actividad Cuantitativa , Moduladores de Tubulina/química

RESUMEN

A series of metronidazole­thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, (1)H NMR and MS. They were also tested for antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5 e exhibited the most potent inhibitory activity against E. coli FabH with IC50 of 4.9 lM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5 a, 5 b, 5 d, 5 e, 5 g and 5 i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability.

Asunto(s)

Antibacterianos/síntesis química , Antibacterianos/farmacología , Diseño de Fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Metronidazol/química , Tiazoles/química , 3-Oxoacil-(Proteína Transportadora de Acil) Sintasa , Acetiltransferasas/antagonistas & inhibidores , Acetiltransferasas/metabolismo , Antibacterianos/metabolismo , Sitios de Unión , Línea Celular , Supervivencia Celular/efectos de los fármacos , Escherichia coli/metabolismo , Proteínas de Escherichia coli/antagonistas & inhibidores , Proteínas de Escherichia coli/metabolismo , Acido Graso Sintasa Tipo II/antagonistas & inhibidores , Acido Graso Sintasa Tipo II/metabolismo , Humanos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Terciaria de Proteína

RESUMEN

4-Anilinoquinazolines as an important class of protein kinase inhibitor are widely investigated for epidermal growth factor receptor (EGFR) tyrosine kinase or epidermal growth factor receptor 2 (HER2) inhibition. A series of novel 6-salicyl-4-anilinoquinazoline derivatives 9-27 were prepared and evaluated for their EGFR/HER2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on three variant cancer cell lines (A431, MCF-7, and A549). The bioassay results showed most of the designed compounds exhibited moderate to potent in vitro inhibitory activity in the enzymatic and cellular assays, of which compound 21 revealed the most potent dual EGFR/HER2 inhibitory activity, with IC50 values of 0.12 µM and 0.096 µM, respectively, comparable to the control compounds Erlotinib and Lapatinib. Furthermore, the kinase selectivity profile of 21 was accessed and demonstrated its good selectivity over the majority of the close kinase targets. Docking simulation was performed to position compound 21 into the EGFR/HER2 active site to determine the probable binding pose. These new findings along with molecular docking observations could provide an important basis for further development of compound 21 as a potent EGFR/HER2 dual kinase inhibitor.

Asunto(s)

Benzamidas/química , Benzamidas/farmacología , Diseño de Fármacos , Receptores ErbB/antagonistas & inhibidores , Quinazolinas/química , Quinazolinas/farmacología , Receptor ErbB-2/antagonistas & inhibidores , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Benzamidas/metabolismo , Dominio Catalítico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Receptores ErbB/química , Receptores ErbB/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/metabolismo , Receptor ErbB-2/química , Receptor ErbB-2/metabolismo , Relación Estructura-Actividad

RESUMEN

A series of novel 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives had been designed, synthesized, isolated and evaluated as potentiators of antibacterial agents. All these synthesized compounds were determined by elemental analysis, (1)H NMR, and MS. Their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus thuringiensis and Bacillus subtilis by MTT method as potential FabH inhibitory. The results showed that compound 30 exhibited the most potent E. coli FabH inhibitory activity with IC50 of 4.6 µM. Molecular modeling simulation studies were performed in order to predict the biological activities of the proposed compounds. All compounds have been tested for toxicity by MTT assay on human macrophage.

Asunto(s)

Antibacterianos/farmacología , Bacillus subtilis/efectos de los fármacos , Bacillus thuringiensis/efectos de los fármacos , Diseño de Fármacos , Escherichia coli/efectos de los fármacos , Nitroimidazoles/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Relación Dosis-Respuesta a Droga , Humanos , Macrófagos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Nitroimidazoles/síntesis química , Nitroimidazoles/química , Relación Estructura-Actividad

RESUMEN

A series of sulfonamides containing coumarin moieties had been prepared that showed a very interesting profile for the inhibition of two human carbonic anhydrase inhibitors. These compounds were evaluated for their ability to inhibit the enzymatic activity of the physiologically dominant isozymes hCA II and the tumor-associated isozyme hCA IX. The most potent inhibitor against hCA II and IX were compounds 5d (IC50 = 23 nM) and 5l (IC50 = 24 nM), respectively. These sulfonamides containing coumarin moieties may prove interesting lead candidates to target tumor-associated CA isozymes, wherein the CA domain is located extracellularly. Eighteen compounds were scrutinized by CoMFA and CoMSIA techniques of 3D quantitative structure-activity relationship. Nine of the compounds were evaluated for cytotoxicity against human macrophage.

Asunto(s)

Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica IV/antagonistas & inhibidores , Cumarinas/química , Cumarinas/farmacología , Diseño de Fármacos , Relación Estructura-Actividad Cuantitativa , Sulfonamidas/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Anhidrasa Carbónica II/química , Anhidrasa Carbónica II/metabolismo , Anhidrasa Carbónica IV/química , Anhidrasa Carbónica IV/metabolismo , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/metabolismo , Inhibidores de Anhidrasa Carbónica/farmacología , Técnicas de Química Sintética , Cumarinas/síntesis química , Cumarinas/metabolismo , Humanos , Isoenzimas/antagonistas & inhibidores , Isoenzimas/química , Isoenzimas/metabolismo , Células MCF-7 , Melanoma Experimental , Simulación del Acoplamiento Molecular , Conformación Proteica , Especificidad por Sustrato