Towards breast cancer targeting: Synthesis of tetrahydroindolocarbazoles, antibreast cancer evaluation, uPA inhibition, molecular genetic and molecular modelling studies.

Entesar M Ahmed,Alaadin E Sarhan,Dina H El-Naggar,Reham R Khattab,Mohamed El-Naggar,Shahenda M El-Messery,Ghada S Hassan,Marwa M Mounier,Khaled Mahmoud,Neama I Ali,Karima F Mahrous,Mamdouh M Ali,Mardia T El Sayed

Bioorganic Chemistry（2019）

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摘要

•New series of tetrahydroindolocarbazole derivatives has been synthesized.•Compound 11 expressed GI% values of 99.9% against MCF7 breast cancer cell line compared to Doxurubucin.•Compound 11 showed a remarkable decrease of uPA level to 3.5 ng/ml compared to DOX.•Compounds 5, 11 and 15 showed significant decrease in expression of MTAP and CDKN2A.•Compounds 5, 11 showed remarkable binding uPA active site via hydrogen binding interactions.

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关键词

Breast cancer,Tetrahydroindolocarbazoles,Urokinase inhibition,DNA genetics,Molecular modelling studies

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