Topo II inhibition and DNA intercalation by new phthalazine-based derivatives as potent anticancer agents: design, synthesis, anti-proliferative, docking, and in vivo studies.
J Enzyme Inhib Med Chem
; 37(1): 299-314, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-34894955
ABSTRACT
This research presents the design and synthesis of a novel series of phthalazine derivatives as Topo II inhibitors, DNA intercalators, and cytotoxic agents. In vitro testing of the new compounds against HepG-2, MCF-7, and HCT-116 cell lines confirmed their potent cytotoxic activity with low IC50 values. Topo II inhibition and DNA intercalating activities were evaluated for the most cytotoxic members. IC50 values determination demonstrated Topo II inhibitory activities and DNA intercalating affinities of the tested compounds at a micromolar level. Amongst, compound 9d was the most potent member. It inhibited Topo II enzyme at IC50 value of 7.02 ± 0.54 µM with DNA intercalating IC50 of 26.19 ± 1.14 µM. Compound 9d was then subjected to an in vivo antitumor examination. It inhibited tumour proliferation reducing solid tumour volume and mass. Additionally, it restored liver enzymes, proteins, and CBC parameters near-normal, indicating a remarkable amelioration in their functions along with histopathological examinations.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Ftalazinas
/
DNA
/
Desenho de Fármacos
/
DNA Topoisomerases Tipo II
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Inibidores da Topoisomerase II
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Simulação de Acoplamento Molecular
/
Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Egito