RESUMEN

[This corrects the article DOI: 10.3389/fmicb.2024.1346251.].

RESUMEN

Vibrio parahaemolyticus is a food-borne pathogen, which is often isolated from various seafood products. In this study, two kinds of bacteriophages was isolated from the offshore sediments samples. The anti-phage mutant strain were obtained after seventeen rounds of co-culture of Vibrio parahaemolyticus and mixed bacteriophage, multigroup sequencing was carried out on spontaneous the anti-phage mutant strain and the wild-type strain. We used the Sanger sequencing to verify the accuracy of the mutation sites. Biolog GEN III MicroPlates were used to evaluate the metabolic capacity of wild-type strains and the anti-phage mutant strain. In this study, we found that with flaG gene (slight homology to N terminus of multiple flagellins) mutated, making the bacteriophage unable to absorb to the cell surface of the host. And, the growth competitiveness of the anti-phage mutant strain is lower than the wild-type strain. These results indicated that the fitness cost, including loss of the growth competitiveness, constitutes a barrier to the prevalence of these defense mechanisms. And the selection pressure on different anti-phage strategies depends on the trade-off between mortality imposed by bacteriophages and fitness cost of the defense strategy under the given environmental conditions. In conclusion, this study provides valuable insights into the phage-host interaction and phage resistance in Vibrio parahaemolyticus. Our study provided knowledge for the evolutionary adaption of bacteria against the bacteriophage, which could add more information to understand the phage resistance mechanism before applying in the industry.

RESUMEN

In sulfate radical-based advanced oxidation processes (SR-AOPs), high-efficiency and perdurable materials have drawn considerable interest for use as cathodes, which can effectively degrade refractory organic contaminants through the synergistic electro-activation and transition metal activation of persulfate (PS). Here, the FeCuO@C modified composite cathode (FeCuO@C/AGF) was synthesized via the solvothermal and thermal treatment method based on the CuFe-MOF-74 structure, and the electro-activation PS process (EC/FeCuO@C/AGF/PS) was developed to effectively remove atrazine (ATZ). The surface morphology, electrochemical characteristics, chemical composition, crystal structure, and electrode surface wettability of FeCuO@C/AGF were investigated. It was found that the proposed EC/FeCuO@C/AGF/PS process can successfully remove 100% of ATZ in 20 min at a low current density (2 mA cm-2) and a low PS concentration (0.4 mM), and PS is successfully activated by combining the electrical and transition metal synergistic activation. The FeCuO@C/AGF cathode exhibits outstanding catalytic functionality over a broad pH range (2-9) and remains stable over five successive cycles. Additionally, the active species involved in the reaction as well as the potential ATZ degradation reaction mechanisms and pathways are discussed. Electrochemical oxidation is a process in which both radicals (SO4·-, ·OH, and O2·-) and non-radical (1O2) participate in the degradation of ATZ. The intermediates of the ATZ degradation process were studied upon the toxicity changing, and the toxicity of the intermediates was found to be reduced during degradation. These results present a novel approach toward the establishment of an effective and reliable electrode in SR-AOPs that can efficiently treat pesticide wastewater.

Asunto(s)

Atrazina , Contaminantes Químicos del Agua , Atrazina/química , Sulfatos , Aguas Residuales , Oxidación-Reducción , Electrodos , Contaminantes Químicos del Agua/análisis

RESUMEN

Background: Colorectal cancer (CRC) is a common global malignancy associated with high invasiveness, high metastasis, and poor prognosis. CRC commonly metastasizes to the liver, where the treatment of metastasis is both difficult and an important topic in current CRC management. Methods: Microarrays data of human CRC with liver metastasis (CRCLM) were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database to identify potential key genes. Differentially expressed (DE) genes (DEGs) and DEmiRNAs of primary CRC tumor tissues and metastatic liver tissues were identified. Microenvironment Cell Populations (MCP)-counter was used to estimate the abundance of immune cells in the tumor micro-environment (TME), and weighted gene correlation network analysis (WGCNA) was used to construct the co-expression network analysis. Gene Ontology and Kyoto Encyclopaedia of Gene and Genome (KEGG) pathway enrichment analyses were conducted, and the protein-protein interaction (PPI) network for the DEGs were constructed and gene modules were screened. Results: Thirty-five pairs of matched colorectal primary cancer and liver metastatic gene expression profiles were screened, and 610 DEGs (265 up-regulated and 345 down-regulated) and 284 DEmiRNAs were identified. The DEGs were mainly enriched in the complement and coagulation cascade pathways and renin secretion. Immune infiltrating cells including neutrophils, monocytic lineage, and cancer-associated fibroblasts (CAFs) differed significantly between primary tumor tissues and metastatic liver tissues. WGCN analysis obtained 12 modules and identified 62 genes with significant interactions which were mainly related to complement and coagulation cascade and the focal adhesion pathway. The best subset regression analysis and backward stepwise regression analysis were performed, and eight genes were determined, including F10, FGG, KNG1, MBL2, PROC, SERPINA1, CAV1, and SPP1. Further analysis showed four genes, including FGG, KNG1, CAV1, and SPP1 were significantly associated with CRCLM. Conclusions: Our study implies complement and coagulation cascade and the focal adhesion pathway play a significant role in the development and progression of CRCLM, and FGG, KNG1, CAV1, and SPP1 may be metastatic markers for its early diagnosis.

RESUMEN

Background: Globally, the incidence and mortality of colorectal cancer (CRC) rank amongst the highest of all malignancies. Thus, research aimed at developing new screening strategies and biomarkers for the early detection of CRC is needed. At present, conventional screening methods have limitations; therefore, new testing strategies have been considered. Using metabolomics to explore the molecular changes in CRC tissue is a mainstream method for identifying potential biomarkers and key cancer factors. Methods: In the present study, 27 samples from nine CRC patients were used to analyze the metabolite differences between the tumor, paracancerous, and normal tissues. The metabolite differences in the various stages of CRC (stages IIA, IIB, and IIIC) were analyzed as well. Subsequently, principal component analysis (PCA), permutation, and trend analyses were performed. Weighted gene co-expression and metabolite-metabolite interaction networks were also constructed. Results: A total of 5,834 metabolites were identified among the included samples. Permutation analysis showed a clear separation between the different tissues and different stages. Compared with normal tissues, tumor tissues exhibited 11, 233, and 25 up-regulated metabolites as well as one, 77, and zero down-regulated metabolites in stages IIA, IIB, and IIIC, respectively. Moreover, tumor tissues in stage IIB exhibited more differential metabolites (233 up-regulated and 77 down-regulated). Weighted Gene Correlation Network Analysis (WGCNA) clustered the 5,834 metabolites into 15 different modules, of which four modules were significantly correlated with tissue specificity. Notably, glycerophospholipid metabolism, fatty acid metabolism, and other pathways were enriched in these modules. Conclusions: Fatty acids and glycerophospholipids were significantly related to the development of CRC. This result is of great significance for future targeted screening of CRC biomarkers and further clarifying the nutrient metabolism of cancer cells.

RESUMEN

A novel series of 4-(4-formamidophenylamino)-N-methylpicolinamide derivatives were synthesized and evaluated against different tumor cell lines. Experiments in vitro showed that these derivatives could inhibit the proliferation of two kinds of human cancer cell lines (HepG2, HCT116) at low micromolar concentrations and the most potent analog 5q possessed broad-spectrum antiproliferative activity. Experiments in vivo demonstrated that 5q could effectively prolong the longevity of colon carcinoma-burdened mice and slow down the progression of cancer cells by suppression of angiogenesis and the induction of apoptosis and necrosis.

Asunto(s)

Antineoplásicos/farmacología , Ácidos Picolínicos/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Ácidos Picolínicos/síntesis química , Ácidos Picolínicos/química , Células Tumorales Cultivadas

RESUMEN

Porcine circovirus 3 (PCV3) infections have been reported in different clinical presentations. However, the prevalence and pathogenicity of PCV3 associated with diarrhea in piglets have been limited. Herein, we present an investigation and genome analyses of PCV3 in piglets experiencing diarrhea, and observed clinical signs, gross lesions, and histological changes in pigs negative for all known pathogens associated with diarrhea but positive for PCV3 alone. Among the feces (n = 141) tested, 16.31% (23/141) were positive for PCV3. Of which, 27.28% (15/55) and 14.29% (5/35) were present in diarrheal samples from suckling and weaned piglets, respectively. Moderate to severe atrophic villi was confined in duodenum, jejunum, and ileum, and significantly decreased average heights of villi, and the depths of crypt were observed in PCV3-infected piglets. The complete genome of a representative strain of PCV3, designated as JX/CH/2018, was determined. Multialignment analysis indicated that JX/CH/2018 had 97.7-99.7% nucleotide identity at the complete genome level, and 97.2-100% at the amino acid level of the capsid protein when compared with reference PCV3 strains. Phylogenetic analysis showed that the PCV3 strain identified in this study belonged to PCV3a lineage. The present study demonstrated that PCV3 is a common virus in diarrheal suckling and weaned piglets.

RESUMEN

Artesunate (AS), a famous derivative of the artemisinin, is the basic treatment globally for mild to severe malaria infection due to the prominent advantages such as high efficiency, fast effect, low toxicity and not easy to produce resistance. More and more research reports have shown that AS and its active metabolites dihydroartemisinin (DHA) had various bioactivities in addition to antimalarial activity, attracting researchers to further study its new pharmacological effects in order to explore new use of the old drug. A comprehensive understanding of the pharmacokinetic characteristics of AS will be conducive to the further development of new pharmacological actions and clinical application of AS. Therefore, this paper would review the absorption, distribution, metabolism and excretion of AS in vivo, as well as the pharmacokinetics characteristics of AS and DHA after clinical administration of AS by intravenous (IV), intramuscular (IM), oral or rectal routes. The in vivo process and pharmacokinetic parameters of AS and DHA were compared between healthy volunteers, malaria patients, and special populations (children, women). Meanwhile, the research progress on pharmacological effects of AS and active metabolite DHA such as anti-tumor, anti-inflammatory, anti septic, antiangiogenic, anti-fibrosis and immunoregulation activities would be also reviewed, hoping to provide a theoretical basis for the further development and utilization of AS and its metabolites.

Asunto(s)

Antimaláricos/farmacología , Antimaláricos/farmacocinética , Artesunato/farmacología , Artesunato/farmacocinética , Humanos , Investigación

RESUMEN

New chemotherapeutic compounds and regimens are needed to combat multidrug-resistant Mycobacterium tuberculosis. Here, we used a series of murine models to assess an antitubercular lead compound SKLB-TB1001. In the Mycobacterium bovis bacillus Calmette-Guérin and the acute M. tuberculosis H37Rv infection mouse models, SKLB-TB1001 significantly attenuated the mycobacterial load in lungs and spleens. The colony forming unit counts and histological examination of lungs from H37Rv infected mice revealed that the benzothiazinethione analogue SKLB-TB1001 as a higher dose level was as effective as isoniazid. Moreover, in a multidrug-resistant (MDR)-TB mouse model, SKLB-TB1001 showed significant activity in a dose-dependent manner and was more effective than streptomycin. These results suggested that SKLB-TB1001 could be an antitubercular drug candidate worth further investigation.

Asunto(s)

Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Tiadiazoles/farmacología , Animales , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Femenino , Pulmón/efectos de los fármacos , Pulmón/microbiología , Pulmón/patología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Análisis de Supervivencia , Tiadiazoles/síntesis química , Tiadiazoles/química , Tiadiazoles/uso terapéutico , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Tuberculosis/patología

RESUMEN

The design, synthesis, and SAR studies of novel inhibitors of HCV NS4B based on the imidazo[2,1-b]thiazole scaffold were described. Optimization of potency with respect to genotype 1b resulted in the discovery of two potent leads 26f (EC50 = 16 nM) and 28g (EC50 = 31 nM). The resistance profile studies revealed that 26f and 28g targeted HCV NS4B, more precisely the second amphipathic α helix of NS4B (4BAH2). Cross-resistance between our 4BAH2 inhibitors and other direct-acting antiviral agents targeting NS3/4A, NS5A, and NS5B was not observed. For the first time, the synergism of a series of combinations based on 4BAH2 inhibitors was evaluated. The results demonstrated that our 4BAH2 inhibitor 26f was synergistic with NS3/4A inhibitor simeprevir, NS5A inhibitor daclatasvir, and NS5B inhibitor sofosbuvir, and it could also reduce the dose of these drugs at almost all effect levels. Our study suggested that favorable effects could be achieved by combining 4BAH2 inhibitors such as 26f with these approved drugs and that new all-oral antiviral combinations based on 4BAH2 inhibitors were worth developing to supplement or even replace current treatment regimens for curing HCV infection.

Asunto(s)

Antivirales/química , Antivirales/farmacología , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Tiazoles/química , Tiazoles/farmacología , Proteínas no Estructurales Virales/antagonistas & inhibidores , Línea Celular , Sinergismo Farmacológico , Genotipo , Hepacivirus/genética , Hepacivirus/metabolismo , Hepatitis C/virología , Humanos , Mutación , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo

RESUMEN

Current treatment for hepatitis C is barely satisfactory, there is an urgent need to develop novel agents for combating hepatitis C virus infection. This study discovered a new class of thieno[2,3-b]pyridine derivatives as HCV inhibitors. First, a hit compound characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. And then, structure activity relationship study of the hit compound led to the discovery of several potent compounds without obvious cytotoxicity in vitro (12c, EC50=3.3µM, SI >30.3, 12b, EC50=3.5µM, SI >28.6, 10l, EC50=3.9µM, SI >25.6, 12o, EC50=4.5µM, SI >22.2, respectively). Although the mechanism of them had not been clearly elucidated, our preliminary optimization of this class of compounds had provided us a start point to develop new anti-HCV agents.

Asunto(s)

Antivirales/química , Antivirales/farmacología , Hepacivirus/efectos de los fármacos , Piridinas/química , Antivirales/síntesis química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Células HEK293 , Humanos , Piridinas/síntesis química , Piridinas/farmacología , Piridinas/toxicidad , Relación Estructura-Actividad , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas no Estructurales Virales/metabolismo , Replicación Viral/efectos de los fármacos

RESUMEN

N-Alkyl and heterocycle substituted 1,3-benzothiazin-4-one (BTZ) derivatives were synthesized. The anti-mycobacterial activities of these compounds were evaluated by determination of minimal inhibitory concentration (MIC) for Mycobacterium tuberculosis H37Ra and M. tuberculosis H37Rv. It was found that an extended or branched alkyl chain analog could enhance the potency, and activities of N-alkyl substituted BTZs were not affected by either nitro or trifluoromethyl at 6-position. Trifluoromethyl plays an important role in maintaining anti-tubercular activity in the piperazine or piperidine analogs. Compound 8o, which contains an azaspirodithiolane group, showed a MIC of 0.0001 µM against M. tuberculosis H37Rv, 20-fold more potent than BTZ043 racemate. These results suggested that the volume and lipophilicity of the substituents were important in maintaining activity. In addition, compound 8o was nontoxic to Vero cells and orally bioavailable in a preliminary pharmacokinetics study.

Asunto(s)

Antituberculosos/química , Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Tiazinas/química , Tiazinas/farmacología , Animales , Antituberculosos/síntesis química , Antituberculosos/farmacocinética , Chlorocebus aethiops , Humanos , Ratas , Ratas Sprague-Dawley , Compuestos de Espiro/síntesis química , Compuestos de Espiro/farmacocinética , Relación Estructura-Actividad , Tiazinas/síntesis química , Tiazinas/farmacocinética , Tuberculosis/tratamiento farmacológico , Células Vero

RESUMEN

Hepatocellular carcinoma is one of the most common cancers in worldwide. We previously reported a novel thienopyridine derivative 3-amino-6-(3,4-dichlorophenyl) thieno[2,3-b]pyridine-2-carboxamide (SKLB70359) which possesses anticancer activity against hepatocellular carcinoma. In present study, we further investigated its anticancer activity and possible mechanism. The SKLB70359 treatment decreased the viability of a panel of hepatocellular carcinoma cell lines in a concentration- and time-dependent manner with IC(50) 0.4 ~ 2.5 µM. The mechanism study showed that SKLB70359 induced G0/G1 cell cycle arrest and then led to apoptotic cell death of HepG2 cell. The SKLB70359 induced G0/G1 cell cycle arrest was characterized by down-regulation of cyclin-dependent kinase 2 (CDK2), CDK4, CDK6 expression and up-regulation of p53, p21(WAF1). Activating of caspase-3 and caspase-9 was also observed. Meanwhile, proliferation inhibitory effect of SKLB70359 was associated with decreased level of phosphorylated p44/42 mitogen activated protein kinase (p44/42 MAPK) and phosphorylated retinoblastoma protein (Rb). Moreover, SKLB70359 exhibit less toxicity to non-cancer cells than tumor cells. In conclusion, the findings in this study suggested that SKLB70359 have potential anticancer efficacy via G0/G1 cell cycle arrest and apoptosis induction. Its potential to be a candidate of anticancer agent is worth being further investigated.

Asunto(s)

Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Piridinas/farmacología , Tiofenos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quinasa 2 Dependiente de la Ciclina/metabolismo , Quinasa 4 Dependiente de la Ciclina/metabolismo , Quinasa 6 Dependiente de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosforilación , Piridinas/química , Piridinas/uso terapéutico , Proteína de Retinoblastoma/metabolismo , Tiofenos/química , Tiofenos/uso terapéutico , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba

RESUMEN

Antagonizing angiogenesis-related receptor tyrosine kinase is a promising therapeutic strategy in oncology. In present study, we designed and synthesized a novel vascular endothelial growth factor receptor (VEGFR) inhibitor N-methyl-4-(4-(3-(trifluoromethyl) benzamido) phenoxy) picolinamide SKLB610 that potently suppresses human tumor angiogenesis. SKLB610 inhibited angiogenesis-related tyrosine kinase VEGFR2, fibroblast growth factor receptor 2 (FGFR2) and platelet-derived growth factor receptor (PDGFR) at rate of 97%, 65% and 55%, respectively, at concentration of 10µM in biochemical kinase assays. In vitro, SKLB610 showed more selective inhibition of VEGF-stimulated human umbilical vein endothelial cells (HUVECs) proliferation, and this proliferation inhibitory effect was associated with decreased phosphorylation of VEGFR2 and p42/44 mitogen-activated protein kinase (p42/44 MAPK). Antiangiogenic evaluation showed that SKLB610 inhibited the HUVECs capillary-tube formation on Matrigel in vitro and the sub-intestinal vein formation of zebrafish in vivo. Moreover, SKLB610 inhibited a panel of human cancer cells proliferation in a concentration-dependent manner and human non-small cell lung cancer cell line A549 and human colorectal cancer cell line HCT116 were most sensitive to SKLB610 treatment. In vivo, chronic intraperitoneally administration of SKLB610 at dose of 50mg/kg/d resulted in significant inhibition in the growth of established human A549 and HCT116 tumor xenografts in nude mice without exhibit toxicity. Histological analysis showed significant reductions in intratumoral microvessel density (CD31 staining) of 43-55% relative to controls depending on the specific tumor xenografts. In conclusion, the present study demonstrated that SKLB610 exhibited its antitumor activity as a multi-targeted inhibitor with more potent inhibition of VEGFR2 activity. Its potential to be a candidate of anticancer agent is worth being further investigated.

Asunto(s)

Inhibidores de la Angiogénesis/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Neovascularización Patológica/tratamiento farmacológico , Ácidos Picolínicos/farmacología , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptores del Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Amidas/síntesis química , Amidas/farmacología , Inhibidores de la Angiogénesis/síntesis química , Animales , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colágeno/metabolismo , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Femenino , Humanos , Laminina/metabolismo , Ratones , Ratones Desnudos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Fosforilación/efectos de los fármacos , Ácidos Picolínicos/síntesis química , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/farmacología , Proteoglicanos/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptores del Factor de Crecimiento Derivado de Plaquetas/metabolismo , Venas Umbilicales/citología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Pez Cebra

RESUMEN

Novel thienopyridine derivatives 1b-1r were synthesized, based on a hit compound 1a that was found in a previous cell-based screening of anticancer drugs. Compounds 1a-1r have the following features: (1) their anticancer activity in vitro was first reported by our group. (2) The most potent analog 1g possesses hepatocellular carcinoma (HCC)-specific anticancer activity. It can specifically inhibit the proliferation of the human hepatoma HepG2 cells with an IC(50) value of 0.016µM (compared with doxorubicin as a positive control, whose IC(50) was 0.37µM). It is inactive toward a panel of five different types of human cancer cell lines. (3) Compound 1g remarkably induces G(0)/G(1) arrest and apoptosis in HepG2 cells in vitro at low micromolar concentrations. These results, especially the HCC-specific anticancer activity of 1g, suggest their potential in targeted chemotherapy for HCC.

Asunto(s)

Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Tienopiridinas/síntesis química , Tienopiridinas/farmacología , Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclización , ADN/biosíntesis , ADN/genética , Doxorrubicina/farmacología , Citometría de Flujo , Fase G1/efectos de los fármacos , Humanos , Espectroscopía de Resonancia Magnética , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Espectrometría de Masa por Ionización de Electrospray , Relación Estructura-Actividad

RESUMEN

The mol-ecule of the title compound, C(10)H(9)N(3)S, is almost planar, with a dihedral angle of 1.38 (4)° between the thio-phene and pyridine rings. In the crystal packing, mol-ecules are linked into layers parallel to the ab plane by inter-molecular N-H⋯N hydrogen bonds and by π⋯π stacking inter-actions involving adjacent pyridine and thio-phene rings with a centroid-centroid distance of 3.537 (3) Å.