A novel quinine derivative as a PIM-1 kinase inhibitor induces apoptosis via mitochondrial depolarization with selective cytotoxicity in acute lymphoblastic leukemia cells

Background: Acute lymphoblastic leukemia (ALL) remains a major therapeutic challenge, particularly in adult patients with poor tolerance to intensive chemotherapy, underscoring the need for novel and selective antileukemic agents that target more specific pharmacological targets and contribute to the development of new, less invasive therapeutic interventions. Quinine, a natural alkaloid, and its derivatives have demonstrated promising anticancer properties that could contribute to this development. Purpose: cytotoxicity was evaluated against CEM and Jurkat leukemia cell lines and non-cancerous fibroblasts (Hs-27). To elucidate the mechanism of action, analyses revealed a strong affinity of the compounds for PIM-1 kinase, a protein overexpressed in most cases of ALL. Results and discussion: , and PIM-1 kinase, supported by favorable MM/GBSA binding free energy values. Conclusion: as a promising PIM-1 kinase-targeting antileukemic candidate.