RESUMEN
3 series of novel fused heterocyclic systems, viz. triazolo[4,3-a]quinazolin-7-ones (3), 1 2 4 5-tetrazino[4,3-a]-quinazolin-8-ones (5) and Schiff's bases of isatin derivatives with 2-hydrazinoquinazolin-4-ones (7) have been synthesized. Several of them showed variable and promising in vitro antiproliferative activity against the MCF-7 cells. Compounds 3a-3c, 6, 7a-7 f showed promising activity (IC50=12.45-15.79 µM). Compound 7 f possessed notable cell cycle disrupting and apoptotic activities with enhanced selectivity against cancer cells, suggesting the potential for the development of new selective cell cycle inhibitors. In silico docking study of the compound 7 f with EGFR enzyme postulated that the designed compound might act on the same enzyme target where DJK_3021_A x-ray structure acted.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Quinazolinas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Receptores ErbB/antagonistas & inhibidores , Femenino , Humanos , Concentración 50 Inhibidora , Isatina/síntesis química , Isatina/química , Isatina/farmacología , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Simulación del Acoplamiento Molecular , Quinazolinas/síntesis química , Quinazolinas/química , Relación Estructura-ActividadRESUMEN
Ketorolac tromethamine (KT), a non-steroidal anti-inflammatory drug, was formulated in buccoadhesive film to overcome the limitations in the currently available routes of administration which in sequence will increase patients' compliance. The film was formulated using aqueous solvents by means of two bioadhesive polymers namely: hydroxylpropyl methyl cellulose (HPMC) and Carbopol 934. The prepared film was subjected to investigations for its physical and mechanical properties, swelling behavior, in vitro bioadhesion, and in vitro, in situ and in vivo release. Anti-inflammatory efficacy and analgesic activity of the prepared buccoadhesive film were investigated in rats using the hind-paw oedema test and the hot plate method. The analgesic efficacy and tolerability of a single 30 mg dose of KT formulated into the buccoadhesive film was clinically evaluated using a standard, widely accepted post-oral surgery pain model. In this study, the prepared film has been administrated to dental post-operative patients for relieving pain in dental hospital clinic. Results indicate that the concentration of KT in the oral cavity was maintained above 4.0 microg/ml for a period of at least 6 h. The buccal KT film was excellently tolerated in all patients and no complains of GI side effects were reported. It is concluded from this clinical evaluation that KT formulated into a buccoadhesive film is effective as a potent analgesic in dental and postoperative oral surgery in a single dose of 30 mg with minimal GI side effects.