Synthesis and Primary Biological Evaluation of Triazole‐Modified Picroside II Compounds

Abstract Picroside II, an iridoid glycoside, has anti‐cancer, anti‐virus, anti‐apoptotic, nervous and myocardial protection effects and so on. However, the oral bioavailability of Picroside II is low, and the half‐life in vivo is short, so it is limited to use in clinic. Triazole is a highly stable heterocyclic ring, which can be interacted with various enzymes or receptors in the organism through non‐covalent interactions, and many of its good pharmacological activities in vitro and in vivo have been reported. Based on the advantages of triazole and Picroside II, a series of triazole‐modified Picroside II derivatives ( 5 a – 5 i ) were synthesized by using drug combination principles for the first time. The structures were confirmed by different spectroscopic techniques including 1 H NMR, 13 C NMR and HRMS, and the primary biological evaluation of anti‐breast cancer, anti‐colorectal cancer, the effect on SARS‐CoV‐2 3CL pro inhibitor, and CD47‐SIRPα protein were screened as well. Compound 5 e has anti‐breast cancer activity, and compounds 3 and 5 i have anti‐colorectal cancer activity.