Synthesis, Anti-Inflammatory and Anticancer Activity Evaluation of Some Novel Acridine Derivatives

Acridine and its derivatives have long occupied a special place in medicinal chemistry owing to their broad-spectrum pharmacological activities. In the present study, a series of twelve novel acridine-based compounds (ACD-1 through ACD-12) were designed, synthesized, and characterized with the primary objective of identifying potent antiinflammatory and anticancer agents with an acceptable safety profile. The synthetic route involved a Doebner–Miller condensation reaction followed by nucleophilic substitution, yielding target molecules bearing diverse substituents at the 9-position and on the peripheral aromatic rings. All synthesized compounds were characterized by 1H NMR, 13C NMR, IR, and high-resolution mass spectrometry (HRMS). For anti-inflammatory screening, the compounds were evaluated through in vitro albumin denaturation inhibition, membrane stabilization, and heat-induced hemolysis assays. Compounds ACD-5, ACD-8, and ACD-11 emerged as the most promising anti-inflammatory agents, with ACD-8 showing 78.4% inhibition of albumin denaturation at 500 µg/mL, outperforming the standard drug diclofenac sodium (72.1%). The anticancer potential of the synthesized compounds was assessed against four human cancer cell lines — MCF-7 (breast), HeLa (cervical), A549 (lung), and HCT116 (colon) — using the MTT assay. ACD-5 and ACD-11 exhibited remarkable cytotoxicity, with IC50 values of 3.24 µM and 4.11 µM against MCF-7 cells, respectively, surpassing the reference drug doxorubicin (IC50 = 5.82 µM) in selectivity. Molecular docking studies revealed that these compounds interact favorably with COX-2 and topoisomerase II enzymes through hydrogen bonding and π–π stacking interactions. Furthermore, in silico ADMET profiling indicated drug-like properties consistent with Lipinski's Rule of Five for most derivatives. The combined biological data from this study strongly suggest that these novel acridine derivatives warrant further investigation as leads in anti-inflammatory and anticancer drug discovery.

Ҳали таржима қилинмаган