The Combretastatins, discovered by ASU researchers, are a
series of very potent antineoplastic compounds. Combretastatin A-4 (CA4), the
most potent compound of the family, is currently undergoing phase III human
cancer clinical trials.
ASU researchers have conducted extended SAR on
Combretastatins. They eventually synthesized structural analogs of
Combretastatins A-4, A-3 and their phosphate prodrugs by replacing their C-3
and/or C-5 substituents with halogens (F, Cl, Br and I). These new compounds,
named Halocombstatins, retained the powerful human cancer cell lines inhibitory
activity of CA4. Fluorcombstatin showed particular potency against human
umbilical vein endothelial cells (HUVECs) in vitro (ED50 0.00025 ?g/ml).
The iodo-structural modifications of CA4P could be
particularly interesting as the parent molecule, CA4, has shown good activity in
treating human thyroid carcinoma.
Moreover, the new synthesized compounds generally display
antimicrobial activity. Some diiodocomstatins are very active against N.
gonorrhoeae.
Potential Applications
These novel compounds have applications as:
- Anti-cancer therapeutic agents
- Anti-cancer therapeutic agents with increased specificity
toward thyroid carcinomas
- Anti-microbial therapeutic agents
Benefits and Advantages
- Diversity – Disclosure of a panel of structural
modifications of Combretastatins. The new compounds retain the Combretastatin
A-4 anti-neoplastic activity. Some of them were more particularly designed for
thyroid cancers treatement.
- Synthesis – The new compounds are synthetically
available.
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For more information about the inventor(s) and their
research, please see
Dr.
Pettit's departmental webpage
