Synthesis and biological evaluation of myoseverin derivatives: microtubule assembly inhibitors

Y T Chang; S M Wignall; G R Rosania; N S Gray; S R Hanson; A I Su; J Merlie Jr; H S Moon; S B Sangankar; O Perez; R Heald; P G Schultz

doi:10.1021/jm010451+

Synthesis and biological evaluation of myoseverin derivatives: microtubule assembly inhibitors

J Med Chem. 2001 Dec 20;44(26):4497-500. doi: 10.1021/jm010451+.

Authors

Y T Chang¹, S M Wignall, G R Rosania, N S Gray, S R Hanson, A I Su, J Merlie Jr, H S Moon, S B Sangankar, O Perez, R Heald, P G Schultz

Affiliation

¹ Department of Chemistry, New York University, 100 Washington Square East, New York, New York 10003, USA. yt.chang@nyu.edu

PMID: 11741468
DOI: 10.1021/jm010451+

Abstract

Myoseverin, a trisubstituted purine, inhibits microtubule assembly in vitro, interferes with normal mitotic spindle assembly, and arrests the cell cycle in mitosis in U937 cells. We synthesized a variety of myoseverin derivatives and screened them for inhibition of spindle assembly in Xenopus egg extracts and for microtubule disassembly in vitro. Selected compounds were tested against 60 cancer cell lines at the National Cancer Institute as possible anticancer drug candidates.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Biopolymers
Cell Division / drug effects
Depression, Chemical
Flow Cytometry
Humans
In Vitro Techniques
Oocytes
Purines / chemical synthesis*
Purines / chemistry
Purines / pharmacology
Spindle Apparatus / drug effects
Structure-Activity Relationship
Tissue Extracts
Tubulin / chemistry
U937 Cells
Xenopus laevis

Substances

Antineoplastic Agents
Biopolymers
Purines
Tissue Extracts
Tubulin
myoseverin