Combretastatin-based compounds with therapeutic characteristics: a patent review.
Expert Opin Ther Pat
; 29(9): 703-731, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-31369715
ABSTRACT
Introduction:
Combretastatins represent a potent class of phenolic-stilbene natural products that function as colchicine binding site inhibitors of tubulin polymerization and have been advanced as promising anticancer lead compounds. Among them, combretastatin A-4 is the most potent lead molecule due to its broad spectrum cytotoxicity against a variety of tumors. However, low water solubility due to its high lipophilic nature and inter-conversion of olefinic double bond from more active cis to less active trans-conformation poses limitations to its clinical utility. However, different approaches including prodrugs, salt formations, structural modifications, prevention of inter-conversion of the olefinic bond and changes to the substitution pattern on the rings of combretastatin A-4 were investigated and successfully resulted in different combretastatin-based molecules that demonstrated varying levels of potency against different types of tumors during their in-vitro and in-vivo studies. Areas covered This review covers the patents over a period of 2008-2018. Expert opinion Molecular hybridization and prodrug designing imparted multi-targeted actions to combretastatin derivatives. Currently, various combretastatin derivatives are under clinical trials. These derivatives could be used to treat disorders other than cancer, due to their vascular disrupting action.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bibenzilas
/
Neoplasias
/
Antineoplásicos Fitogênicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Expert Opin Ther Pat
Ano de publicação:
2019
Tipo de documento:
Article