Apigenin is an aglycone of many natural glycosides and is known chemically as 4 ,5,7-trihydroxyflavone.1 The biological and pharmacological activities of apigenin are diverse, which include anti-inflammatory, antioxidant, anticancer, anti-proliferative and anti-spasmodic.2 The chemistry of oxorhenium(V) complexes is receiving increasing attention because of the potential application in medical and chemistry.

Three rhenium complexes with apigenin and it's derivatives were synthesized (Complex 1- C₃₇H₂₉Cl₂O₉PRe, Complex 2-C₃₇H₃₇Cl₂O₉PReSi₂, Complex 3-C₃₄H₂₉Cl₂O₇PRe and acetylated C₁₉H₁₄O₇ and silylated apigenin C₂₇H₃₈O₄Si₂), fully characterized and used for biological studies. Cytotoxicity assessments were conducted using the resazurin reduction assay across multiple cancer cell lines, including HT29 (colorectal adenocarcinoma), Jurkat (T-cell leukemia), LNCaP (prostate cancer), and MCF7 (breast cancer). Cisplatin was used as a standard of care for this experiment.

All three complexes showed significant cytotoxic potential toward Jukart cell line and moderate activity against other cell lines. Furthermore, IC₅₀ values of all complexes were less than 5 µM, and demonstrated enhanced cytotoxic activity compared to the parent ligands in most cases, particularly in leukemia cells (Jurkat), while solid tumor cell lines showed more variable responses. Additionally, two Re compounds were selected for further investigation in dedicated anti-migration and anti-invasion assays.

Taking everything into consideration, rhenium plays a crucial role in disrupting leukemia cell biology. On the other hand, isolated ligands have milder effects, suggesting the complexes’ bioactivity is enhanced by rhenium coordination. These findings will elucidate the molecular mechanisms and identify potential biomarkers. This comprehensive assessment of their physicochemical properties and cytotoxicity has provided valuable data to support the continued development of rhenium compounds as potential anti-cancer agents.