ABSTRACT
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.
Subject(s)
Acridines , Anti-Bacterial Agents , Antineoplastic Agents , Cell Proliferation , Drug Screening Assays, Antitumor , Microbial Sensitivity Tests , Molecular Docking Simulation , Acridines/chemistry , Acridines/pharmacology , Acridines/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Humans , Cell Proliferation/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Molecular Dynamics Simulation , Structure-Activity Relationship , Molecular Structure , Cell Line, Tumor , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/chemical synthesis , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/chemical synthesis , Dose-Response Relationship, Drug , Gram-Positive Bacteria/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/chemical synthesisABSTRACT
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.
