Evaluation of Bioessential Transition Metal Complexes of β-diketonate derivatives as Promising Anticancer Chemotherapeutics

Abstract

This study explored the antitumor potential of two cobalt(II) β-diketonate complexes: Co(phen)₂(acac)₂ (C1) and Co(dpq)₂(acac)₂ (C2). Their antiproliferative activities were tested on human cancer cell lines A549 (lung adenocarcinoma), HepG2 (hepatocellular carcinoma), and SK-OV-3 (ovarian carcinoma) using the MTT assay, comparing results to cisplatin as a benchmark. C2 exhibited superior antiproliferative effects, with IC₅₀ values between 2.1 to 4.5 µM for cancer cells after 24 hours, while C1 showed values of 3.8 to 10.155 µM, both surpassing cisplatin's IC₅₀ of 15.044-67.694 µM. Morphological assessments, including crystal violet and AO/PI staining, alongside DNA laddering and clonogenic assays, confirmed the induction of apoptosis and inhibition of cell proliferation. C2 was minimally toxic to normal Vero cells (IC₅₀ ≈ 98 µM), whereas C1 had moderate toxicity (IC₅₀ ≈ 50 µM), both less than cisplatin (17.523 µM). Flow cytometric analysis revealed that C2 caused S-phase cell cycle arrest. In vivo studies in female Swiss albino mice showed that C2 treatment yielded no significant systemic toxicity in hematological, biochemical, and histopathological evaluations. Overall, C2 demonstrates promising anticancer activity in vitro with high selectivity for cancer cells and favorable in vivo tolerability, suggesting its potential as a safe anticancer candidate with minimal adverse effects.