A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual Inhibitor.
Molecules
; 25(18)2020 Sep 17.
Article
em En
| MEDLINE
| ID: mdl-32957517
ABSTRACT
Natural products are the ideal basis for the design of novel efficient molecular entities. Podophyllotoxin, a naturally occurring cyclolignan, is an example of natural product which displays a high versatility from a biological activity point of view. Based on its unique chemical structure, different derivatives have been synthesized presenting the original antitumoral properties associated with the compound, i.e., the tubulin polymerization inhibition and arising anti-topoisomerase II activity from structural modifications on the cyclolignan skeleton. In this report, we present a novel conjugate or hybrid which chemically combines both biological activities in one single molecule. Chemical design has been planned based in our lead compound, podophyllic aldehyde, as an inhibitor of tubulin polymerization, and in etoposide, an approved antitumoral drug targeting topoisomerase II. The cytotoxicity and selectivity of the novel synthetized hybrid has been evaluated in several cell lines of different solid tumors. In addition, these dual functional effects of the novel compound have been also evaluated by molecular docking approaches.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Podofilotoxina
/
Produtos Biológicos
/
DNA Topoisomerases Tipo II
/
Moduladores de Tubulina
/
Antineoplásicos Fitogênicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article