RESUMEN
In the present study, numerous acridine derivatives A1-A20 were synthesized via aromatic nucleophilic substitution (SNAr) reaction of 9-chloroacridine with carbonyl hydrazides, amines, or phenolic derivatives depending upon facile, novel, and eco-friendly approaches (Microwave and ultrasonication assisted synthesis). The structures of the new compounds were elucidated using spectroscopic methods. The title products were assessed for their antimicrobial, antioxidant, and antiproliferative activities using numerous assays. Promisingly, the investigated compounds mainstream revealed promising antibacterial and anticancer activities. Thereafter, the investigated compounds' expected mode of action was debated by using an array of in silico studies. Compounds A2 and A3 were the most promising antimicrobial agents, while compounds A2, A5, and A7 revealed the most cytotoxic activities. Accordingly, RMSD, RMSF, Rg, and SASA analyses of compounds A2 and A3 were performed, and MMPBSA was calculated. Lastly, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyses of the novel acridine derivatives were investigated. The tested compounds' existing screening results afford an inspiring basis leading to developing new compelling antimicrobial and anticancer agents based on the acridine scaffold.
Asunto(s)
Acridinas , Antibacterianos , Antineoplásicos , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Acridinas/química , Acridinas/farmacología , Acridinas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Humanos , Proliferación Celular/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Simulación de Dinámica Molecular , Relación Estructura-Actividad , Estructura Molecular , Línea Celular Tumoral , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/síntesis química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Relación Dosis-Respuesta a Droga , Bacterias Grampositivas/efectos de los fármacos , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/síntesis químicaRESUMEN
Pyridines containing the galloyl moiety have been prepared utilizing 4-acetyl pyrogallol. In addition, fused pyridines were synthesized from the obtained pyridines via further chemical transformations. The results indicated that compound 4a showed stronger DPPH scavenging activity than the other compounds, and the scavenging effect decreased in the following order 4a > t-BHQ > 2a > 2b > 3a > 3b > 4b. Accordingly, other antioxidant assays were conducted for 4a. The results suggested that compound 4a could be a good antioxidant candidate. The absence of mortality of rats receiving 5000 mg/kg body weight of 4a as single oral dose may indicate that it could be a safe antioxidant and may be used for further studies.
