RESUMEN
Herein, we report the synthesis of different novel sets of coumarin-6-sulfonamide derivatives bearing different functionalities (4a, b, 8a-d, 11a-d, 13a, b, and 15a-c), and in vitro evaluation of their growth inhibitory activity towards the proliferation of three cancer cell lines; HepG2 (hepatocellular carcinoma), MCF-7 (breast cancer), and Caco-2 (colon cancer). HepG2 cells were the most sensitive cells to the influence of the target coumarins. Compounds 13a and 15a emerged as the most active members against HepG2 cells (IC50 = 3.48 ± 0.28 and 5.03 ± 0.39 µM, respectively). Compounds 13a and 15a were able to induce apoptosis in HepG2 cells, as assured by the upregulation of the Bax and downregulation of the Bcl-2, besides boosting caspase-3 levels. Besides, compound 13a induced a significant increase in the percentage of cells at Pre-G1 by 6.4-folds, with concurrent significant arrest in the G2-M phase by 5.4-folds compared to control. Also, 13a displayed significant increase in the percentage of annexin V-FITC positive apoptotic cells from 1.75-13.76%. Moreover, QSAR models were established to explore the structural requirements controlling the anti-proliferative activities.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Cumarinas/química , Relación Estructura-Actividad Cuantitativa , Sulfonamidas/química , Antineoplásicos/síntesis química , Células CACO-2 , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cumarinas/farmacología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Células MCF-7 , Estructura Molecular , Sulfonamidas/farmacologíaRESUMEN
A facile one-pot four-component reaction was utilized to construct 2-oxo-1,2-dihydropyridine-3-carbonitrile as a scaffold for the synthesis of many fused heterocyclic systems, namely, furopyridine, pyridothiadiazepinthione, and pyridotriazine, as well as non-fused heterocyclic systems such as phthalazin-2(1H)-ylnicotinonitrile, pyridin-2-yl-1H-pyrazole, and pyrazol-1-ylnicotino-nitrile,1-(3-cyanopyridin-2-yl)-1H-pyrazole. The new compounds were evaluated as antimicrobial and antiviral agents.
Asunto(s)
Antibacterianos/farmacología , Antivirales/farmacología , Compuestos Heterocíclicos/farmacología , Piridinas/farmacología , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Antivirales/síntesis química , Antivirales/química , Línea Celular , Línea Celular Tumoral , Compuestos Heterocíclicos/síntesis química , Compuestos Heterocíclicos/química , Humanos , Piridinas/síntesis química , Piridinas/química , Relación Estructura-ActividadRESUMEN
A series of eighteen azomethines has been synthesized by the reaction of appropriate primary aromatic amines with aryl and/or heteroaryl carboxaldehydes. The synthesized azomethines have been evaluated for their in vitro antileishmanial, antibacterial and antifungal activities. The results revealed some antifungal activity of most of the synthesized compounds, whereas the antileishmaniasis activity results highlighted that all synthesized azomethines inhibited parasite growth and most of them showed highly potent action towards Leishmania major promastigotes. No remarkable bactericidal activities were observed.