RESUMEN

A new series of triazole-thiazole hybrids were designed, synthesized by the Multi-component reaction approach and evaluated in vitro antimicrobial activity. Most of the tested series of compounds exhibited promising inhibitory activity against the bacterial strains with values in the range of 2.8 to 15.7 µM. The compounds 8i-8l and 8r showed potential-Candida activity against various Candida strains with spectrum values in the range 5.9-14.2 µM. Further, anti-biofilm and toxicity profiles for the potent compounds were also tested, and it was observed that the compounds 8i, 8k, and 8l were found to inhibit the biofilm formation with IC50 values of 6.6, 16.6 and 15.9 µM, respectively against Bacillus subtilis MTCC 121. Besides, 8k and 8l also displayed promising biofilm formation inhibitory activity towards Staphylococcus aureus MTCC 96 with IC50 values of 13.5 and 12.0 µM respectively. In summary, the activity results has emphasized the compounds 8k and 8l as potential leads for further development of antibacterial, anti-Candida, and anti-biofilm agents.

Asunto(s)

Antibacterianos/farmacología , Antifúngicos/farmacología , Tiazoles/farmacología , Triazoles/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Bacillus subtilis/efectos de los fármacos , Biopelículas/efectos de los fármacos , Candida/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Tiazoles/química , Triazoles/química

RESUMEN

As a part of our endeavor toward the synthesis of a new class of biologically potent heterocyclic hybrids, a series of newly fused thiazolo[2,3-b]pyrimidinones bearing a pyrazolylcoumarin moiety (6a-p) were synthesized in acceptable yields. Anticipated structures of all titled compounds were in agreement with spectral and analytical (C, H and N) analyses. The compounds were screened for in vitro antibacterial activity against both G+ and G- bacterial strains and antiproliferative activity against K562 (chronic myelogenous leukemia), MCF-7 (breast cancer), MDA-MB-231 (breast cancer), COLO 205 (colorectal adenocarcinoma), HepG2 (hepatocellular carcinoma) cell lines. Further, potent antibacterial compounds were subjected to molecular docking studies in order to gain insight into their plausible binding modes and mechanism of action against MurB. The modeling results were in agreement with the experimental data.

Asunto(s)

Antibacterianos/síntesis química , Antibacterianos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Simulación del Acoplamiento Molecular , Pirimidinonas/síntesis química , Pirimidinonas/farmacología , Antibacterianos/química , Antibacterianos/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Línea Celular Tumoral , Proteínas de Escherichia coli/antagonistas & inhibidores , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Humanos , Pruebas de Sensibilidad Microbiana , Conformación Proteica , Pirimidinonas/química , Pirimidinonas/metabolismo , Relación Estructura-Actividad

RESUMEN

A series of indole incorporated thiazolylcoumarins (7a-q) have been synthesized and evaluated for their antibacterial, anticancer and DNA cleavage studies. Analysis of antibacterial studies indicated that all the synthesized compounds possess promising activity towards the screened bacterial strains. In vitro anticancerous action was studied for compound 7a (NSC: 768621/1) against the full panel of 60 human tumor cell lines. The five dose level activity results revealed that, the compound 7a was active against all the cell lines among them it has shown potent activity against Leukemia: CCRF-CEM (GI50: 0.33 µM), Non-Small Cell Lung Cancer: NCI-H522 (GI50: 1.03 µM), Colon Cancer: HCT-116 (GI50: 1.60 µM), CNS Cancer: SF-539 (GI50: 1.58 µM), Melanoma MALME-3M (GI50: 1.59 µM), Ovarian Cancer: OVCAR-3 (GI50: 1.16 µM), Renal Cancer: UO-31 (GI50: 0.76 µM), Prostate Cancer: PC-3 (GI50: 0.82 µM) and Breast Cancer: BT-549 (GI50: 1.13 µM). DNA cleavage studies revealed that even at 50 µg/mL concentration complete DNA digestion was observed for all the compounds, except for compound (7o) where partial DNA digestion was observed even at 100 µg/mL.

Asunto(s)

Antibacterianos/síntesis química , Antineoplásicos/síntesis química , Cumarinas/síntesis química , División del ADN/efectos de los fármacos , Indoles/síntesis química , Tiazoles/síntesis química , Antibacterianos/farmacología , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Cumarinas/farmacología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales/métodos , Humanos , Indoles/farmacología , Tiazoles/farmacología

RESUMEN

A series of novel 10-((1H-indol-3-yl)methylene)-7-aryl-7,10-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-9(6H)-ones (8a-t) have been synthesized in good yields by the reaction of benzo[h]quinazoline-2(1H)-thiones (4a-f) with 2-chloro-N-phenylacetamide (5) followed by Knoevenagel condensation with various indole-3-carbaldehydes (7a-d) under conventional method. All the synthesized compounds were characterized by spectral studies and screened for their in vitro anticancer and antimicrobial activities. Compound 8c has exhibited excellent activity against MCF-7 (breast cancer cell line) than the standard drug Doxorubicin. Compound 8d against both the cancer cell lines, 8q against MCF-7 and 8c, 8h against HepG2 have also shown good activity. Remaining compounds have shown moderate activity against both the cell lines. Antimicrobial activity revealed that, the compound 8q and 8t against Staphylococcus aureus and 8i, 8k, 8l, 8q &8t against Klebsiella pneumoniae have shown equipotent activity on comparing with the standard drug Streptomycin. Remaining compounds have shown significant antibacterial and comparable antifungal activities against all the tested microorganisms.

Asunto(s)

Antibacterianos/farmacología , Antifúngicos/farmacología , Antineoplásicos/farmacología , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Quinazolinas/farmacología , Tiazoles/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Aspergillus/efectos de los fármacos , Candida/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Compuestos Heterocíclicos de 4 o más Anillos/síntesis química , Compuestos Heterocíclicos de 4 o más Anillos/química , Humanos , Klebsiella pneumoniae/efectos de los fármacos , Células MCF-7 , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Pseudomonas aeruginosa/efectos de los fármacos , Quinazolinas/síntesis química , Quinazolinas/química , Staphylococcus/efectos de los fármacos , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/química

RESUMEN

Highly efficient and eco-friendly protocol for the synthesis of bis(3-indolyl)methanes by the electrophilic substitution reaction of indole with aldehydes catalyzed by poly(4-vinylpyridinium)hydrogen sulfate was described. Excellent yields, shorter reaction times, simple work-up procedure, avoiding hazardous organic solvents, and reusability of the catalyst are the most obvious advantages of this method.