ABSTRACT:
Cinchonine, an alkaloid found in the bark of various Cinchona species, possesses notable pharmacological properties, including anti‐microbial, anti‐parasitic, anti‐inflammatory, and anti‐obesity effects. Recent research highlights its potential anticancer properties, particularly against leukemia (K562) cells, as its molecular mechanisms remain underexplored. This study assessed cinchonine's antiproliferative effects on K562 cells using NRU, SRB, and MTT assays. It was further investigated for its interactions with molecular targets such as DHFR, COX‐2, 5‐LOX, HYAL, CATD, and ODC through cell‐free and cell‐based systems, docking studies, and qRT‐PCR analysis. Cinchonine inhibited K562 cells growth with an IC
50
of 46.55 µM (NRU assay) and significantly suppressed COX‐2 activity (IC
50
44.65 µM) and expression. It induced G0/G1 cell cycle arrest and increased the sub‐diploid population in K562 cells. In vivo, cinchonine reduced tumor growth in EAC and S‐180 models by 48.49% and 37.86%, respectively, at 50 mg/kg body weight. Toxicity predictions and ex vivo tests confirmed its safety profile. These findings suggest cinchonine as a promising chemopreventive agent for leukemia.