Design, Synthesis, and Evaluation of Antitumor Activity in Pseudolaric acid B Azole Derivatives: Novel and potent Angiogenesis inhibitor via Regulation of the PI3K/AKT and MAPK Mediated HIF-1/VEGF Signaling Pathway

Tumor proliferation and metastasis are intricately linked to blood vessel formation, with vascular endothelial growth factor (VEGF) playing a pivotal role in orchestrating angiogenesis throughout tumor progression. Pseudolaric acid B (PAB) has emerged as a potent inhibitor of tumor cell proliferation, migration, and angiogenesis. In efforts to enhance its efficacy, 37 derivatives of PAB were synthesized and assessed for their capacity to suppress VEGF secretion in SiHa cells under hypoxic conditions. Notably, majority of these derivatives exhibited significant inhibition of VEGF protein secretion without inducing cytotoxicity. Among them, compound M2 displayed the most potent inhibitory activity, with an IC