Crizotinib- or Ceritinib-Conjugated Platinum(IV) Prodrugs As Potent Multiaction Agents Inducing Antiproliferative Effects in 2D and 3D Cancer Cell Models.

ABSTRACT: Novel Pt(IV) complexes conjugated with the kinase inhibitors crizotinib or ceritinib were synthesized and assessed for anticancer activity. Cisplatin-derived derivatives bearing phenylbutyrate and either crizotinib (complex 3) or ceritinib (complex 7) exhibited the greatest efficacy and selectivity against cancer cells while sparing noncancerous counterparts. Both compounds maintained activity in three-dimensional spheroid models, where they reduced viability, inhibited migration, and suppressed invasive outgrowth. Cellular accumulation studies confirmed efficient uptake of 3 and 7. Mechanistic investigations revealed that crizotinib-containing complexes induced G2/M arrest, whereas ceritinib analogs, particularly 7, caused S-phase arrest and DNA damage r

SUBMITTER: Sharkawy S 

PROVIDER: S-EPMC12670396 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature