当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis, state-of-the-art NMR-binding and molecular modeling study of new benzimidazole core derivatives as Pin1 inhibitors: Targeting breast cancer.

Synthesis, state-of-the-art NMR-binding and molecular modeling study of new benzimidazole core derivatives as Pin1 inhibitors: Targeting breast cancer.

Abstract：

:New series of benzimidazole ring core conjugated with either dithiocarbamate or thiopropyl linkers, hybridized with different secondary amines were synthesized; 5-15 and 22-31; respectively. The new compounds were characterized by different spectroscopic techniques (1H, 13C 1D & 2D NMR, ESI-MS and IR). They were screened for in vitro anticancer activity against breast cancer using MCF7 cell line. The results obtained revealed that compounds 5, 12, 15 and 25 were the most active among the synthesized series exhibiting IC50 < 10 µg/ml against DOX. To characterize targeting breast cancer on molecular level, binding to 15N-labeled Pin1 enzyme was conducted using state-of-the-art 2D NMR binding experiments. Results showed promising binding between compounds 5, 12, and 25 by chemical shift perturbation (peak shifting or peak disappearance). Molecular docking study were quite valuable to explain the binding mode of active derivatives via hydrogen bonding. Additional contact preferences and surface mapping studies stated the similarity pattern between active candidates which may pave the way for more precise anti breast cancer target optimization.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Nashaat S,Henen MA,El-Messery SM,Eisa H

doi

10.1016/j.bmc.2020.115495

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

115495

issue

11

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(20)30316-3

journal_volume

28

pub_type

杂志文章

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