Abstract

Boron's unique properties enable organic boronic acid compounds to play a significant role in drug development. Herein, we report the synthesis and anti-HPV activities of a series of novel boronic acid-modified neocryptolepine derivatives, both in vitro and in vivo. The boronic acid-modified compounds 13b and 15 exhibited high anti-HPV activity. However, 13b demonstrated lower cytotoxicity towards HeLa cells, resulting in a higher Selectivity Index (SI). Compound 13b showed inhibitory activity against multiple high-risk HPV strains and could directly inactivate HPV pseudovirions (PsVs) particles. More importantly, 13b significantly inhibited HPV infection in the vaginal tract of BALB/c nude mice. Thus, the boronic acid-modified neocryptolepine derivative 13b possesses anti-HPV activities in vitro and in vivo and may block HPV infection by directly interacting with HPV particles. This suggests that it has great potential to be developed into a novel anti-HPV agent in the future and provides useful information for further research and development of boronic acid-modified anti-HPV drugs.