Bioinspired computational design of lankacidin derivatives for improvement in antitumor activity.
Future Med Chem
; 14(19): 1349-1360, 2022 10.
Article
em En
| MEDLINE
| ID: mdl-36073363
ABSTRACT
Background:
The 17-membered polyketide, lankacidin C, exhibits considerable antitumor activity as a microtubule stabilizer by binding to the paclitaxel binding site.Method:
Esterification of the C-7/C-13 hydroxyl in lankacidin C was performed with acetyl, cinnamoyl and hydrocinnamoyl groups and their antitumor activity was assessed to improve the cytotoxicity of lankacidins through bioinspired computational design.Results:
Compared with the cytotoxicity of parent lankacidin C against the HeLa cell line, 13-O-cinnamoyl-lankacidin C demonstrated sevenfold higher cytotoxicity. Furthermore, 7,13-di-O-cinnamoyl-lankacidin C exhibited considerable antitumor activity against three tested cell lines.Conclusion:
C13-esterification by a cinnamoyl group dramatically improved antitumor activity, in agreement with computational predictions. This finding provides a potential substrate for next-generation lankacidin derivatives with significant antitumor activity.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antibacterianos
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2022
Tipo de documento:
Article