ZFIN Image: Gao et al., 2022, Fig. 1

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Figure Caption

Fig. 1

Design and synthesis. (a) The colchicinoid pharmacophore (gray shaded trimethoxyphenyl south ring and isovanillyl north ring) can be applied to various scaffolds, giving photoswitchable azobenzene-based PST and SBT-based SBTub antimitotics. Previously published SBTub2/3 lacked key interaction residues (red shaded sites). (b) Z-SBTub3 inhibits tubulin polymerization and MT-dependent processes. (c) X-ray structure of tubulin:Z-SBTub3 complex (carbons as purple spheres). The south ring is buried in β-tubulin (green); only the north ring interacts with α-tubulin at the α-T5 loop (cyan). (d) Evolved SBTub compound library used in this paper. (e) Typical synthesis of SBTubs proceeds by acetanilide sulfurization, Jacobson cyclization, and basic condensation. Phosphate prodrug SBTubA4P is further accessed by phosphoester formation and deprotection.

Acknowledgments

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