Design, synthesis, and biological evaluation of X19: a matrine pyrazole derivatives therapeutic candidate

value of 5.92 μM. Mechanistic investigations revealed that X19 suppresses tumor growth through induction of apoptosis, G0/G1 phase cell cycle arrest, and dose-dependent inhibition of the JAK/STAT signaling pathway. In a Huh-7 xenograft mouse model, X19 exhibited significant antitumor efficacy comparable to sorafenib, achieving a tumor growth inhibition rate of 55.35%. Importantly, histopathological evaluation revealed that X19 displays an improved safety profile, particularly demonstrating superior renal protection compared to sorafenib-induced nephrotoxicity, while maintaining manageable toxicity in other major organs. These findings establish X19 as a promising lead compound for hepatocellular carcinoma treatment, representing a significant advancement in the development of matrine-based therapeutics with an optimized therapeutic index.