Inorganic–organic γ-octamolybdate hybrids for targeted anticancer applications against MiaPaca-2 and A549 cells

Cancer is widely recognized as one of the most critical public health challenges, transcending economic boundaries and impacting populations across all socioeconomic strata. Developing effective cancer therapies is significantly hindered by challenges such as chemotherapy-related side effects, drug resistance, and tumor metastasis, which contribute to poor prognoses for many patients. In this context, inorganic drugs, particularly polyoxomolybdate-based inorganic–organic hybrids, are emerging as promising candidates for future metallodrugs. In this study, we report the synthesis of inorganic–organic γ-octamolybdate hybrids, [(C1bipy)²⁺(DMA)²⁺][(Mo₈O₂₆)⁴⁻]·H₂O (1) and [(2,4,6-TMPY)₂⁺(DMA)₂⁺][Mo₈O₂₆]⁴⁻ (2), and characterization by a combined experimental and computational study. The molecular structures of these hybrids were elucidated using single-crystal X-ray diffraction techniques and Hirshfeld analyses. The materials exhibit remarkable stability in aqueous media and demonstrate low toxicity toward normal cell lines. The in vitro cytotoxicity of γ-octamolybdate-based hybrid solids (1 and 2) was systematically evaluated against mammalian pancreatic (MiaPaca-2) and lung (A549) cancer cell lines, revealing their unprecedented potency. 1 exhibited IC₅₀ values of 1.3–2.5 μM for A549 and 3.7–4.1 μM for MiaPaca-2 cells, similarly 2 exhibited exceptional activity, with IC₅₀ values of 1.3–2.5 μM for MiaPaca-2 and 4.1–4.5 μM for A549 cells. Both materials achieved up to 90% inhibition of cell viability at 13 μM, significantly surpassing prior benchmarks. Mechanistic investigations via cell cycle analysis elucidated G1 phase arrest as the pivotal mode of anticancer action, disrupting cellular proliferation with high specificity and potency. These findings evidenced that γ-[Mo₈O₂₆]⁴⁻ hybrids act as robust candidates for therapeutic applications, offering a transformative approach to overcome current limitations in oncological interventions. Thus, this study constitutes the inaugural exploration of γ-octamolybdate-based hybrid materials in anticancer therapy, underscoring their potential for addressing malignancies, particularly pancreatic and lung cancers, at exceptionally low effective concentrations.