Document Type : Original Article
Author
Abstract
This study aimed to develop novel anticancer agents by synthesizing and evaluating
anthraquinone-based heterocyclic compounds as potential inhibitors of Pyruvate Kinase M2
(PKM2) and topoisomerase. Three target compounds incorporating 1,3,4-oxadiazole (Compound
3), 1,2,4-triazole (Compound 5), and 1,3,4-thiadiazole (Compound 6) moieties with an
anthraquinone core were synthesized and characterized using spectroscopic methods (FT-IR, 1HNMR, 13C-NMR). In silico molecular docking revealed that Compound 6 exhibited the highest
binding affinity for both topoisomerase II (ΔG: -8.313 kcal/mol) and PKM2 (ΔG: -9.342 kcal/mol).
ADME predictions indicated all compounds possess high gastrointestinal absorption, are not BBB
permeant, and adhere to Lipinski's rule of five. Cytotoxicity studies (MTT assay) against A549
lung and HepG2 liver cancer cell lines, along with normal HDF cells, demonstrated Compound 6
as the most potent, with IC₅₀ values of 104.37 µg/ml (A549) and 126.59 µg/ml (HepG2).
Compound 6 also showed the highest selectivity for A549 cells (SI: 2.61981). These integrated
findings identify Compound 6 as a promising lead candidate for further investigation in anticancer
drug development
Keywords
)