Design, synthesis, and bioevaluation of pyrazole-containing tubulin polymerisation inhibitors based on conformational constraint strategy.

ABSTRACT: Based on conformational preference of SMART analogues and conformational constraint strategy, two series of new tubulin polymerisation inhibitors (4a - 4k and 5a - 5h/6a - 6h) were designed via hydrogen bonding, steric effect (for 4a - 4k) and ring-closing approach by fused five- and seven-membered ring (for 5a - 5h/6a - 6h) which was first adopted in the design of new SMART analogues. Among these compounds, 4k and 5a showed potent activities with IC₅₀ values of 15 nM and 6 nM against PC-3 cell line. Mechanism studies indicated that 4k and 5a could inhibit tubulin polymerisation, arrest cell cycle at G₂/M phase, induce cell apoptosis, and inhibit cell

SUBMITTER: Sun Z 

PROVIDER: S-EPMC12459184 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature