Design, synthesis and biological evaluation of rhein-piperazine-furanone hybrids as potential anticancer agents.

ABSTRACT: Novel rhein-piperazine-furanone hybrids, 5, were designed and synthesized efficiently from rhein. Cytotoxicity of all hybrids 5a-j against A549 human lung cancer cells was superior to the parent rhein and the reference cytarabine (CAR). Hybrid 5e (IC₅₀ = 5.74 μM), the most potent compound, was 46- and 35-fold more toxic against A549 cells than rhein (IC₅₀ = 265.59 μM) and CAR (IC₅₀ = 202.57 μM), respectively. Moreover, hybrid 5e (IC₅₀ = 69.28 μM) was less toxic to normal WI-38 human lung fibroblast cells with good selectivity (WI-38/A549, SI ≈ 12), being much higher than rhein (SI ≈ 1) and CAR (SI ≈ 2). Structure-activity relationship (SAR) analysis showed that cytotoxicity and selectivity against A549 lung cancer cells were greatly enhanced when

SUBMITTER: He Y 

PROVIDER: S-EPMC10953484 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature