Synthesis of 1-benzyl-1H-benzimidazoles as galectin-1 mediated anticancer agents

被引：31

作者：

Goud, Nerella Sridhar ^{[1
]}

Ghouse, S. Mahammad ^{[1
]}

Vishnu, Jatoth ^{[2
]}

Komal, D. ^{[1
]}

Talla, Venu ^{[2
]}

Alvala, Ravi ^{[3
]}

Pranay, Jakkula ^{[4
]}

Kumar, Janish ^{[4
]}

Qureshi, Insaf A. ^{[4
]}

Alvala, Mallika ^{[1
]}

机构：

[1] NIPER, Dept Med Chem, Hyderabad 500037, India

[2] NIPER, Dept Pharmacol & Toxicol, Hyderabad 500037, India

[3] G Pulla Reddy Coll Pharm, Hyderabad 500028, India

[4] Univ Hyderabad, Sch Life Sci, Dept Biotechnol & Bioinformat, Hyderabad 500046, India

来源：

BIOORGANIC CHEMISTRY | 2019年 / 89卷

关键词：

1-benzyl-1H-benzimidazoles; Galectin-1; Cancer; Fluorescence spectroscopy; RP-HPLC; Surface plasmon resonance; BIOLOGICAL-ACTIVITY; CARCINOMA-CELLS; IN-VITRO; CANCER; APOPTOSIS; GROWTH; DERIVATIVES; EXPRESSION; INHIBITORS; INVASION;

D O I：

10.1016/j.bioorg.2019.103016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In our pursuit to develop novel non-carbohydrate small molecule Galectin-1 Inhibitors, we have designed a series of 1-benzyl-1H-benzimidazole derivatives and demonstrated their anticancer activity. The compound 6g, 4-(1-benzyl-5-chloro-1H-benzo [d] imidazol-2-yl)-N-(4-hydroxyphenyl) benzamide was found to be most potent with an IC50, of 7.01 +/- 0.20 mu M and arresting MCF-7 cell growth at G2/M phase and S phase. Induction of apoptosis was confirmed by morphological changes like cell shrinkage, blebbing and cell wall deformation, dose dependent increase in the mitochondrial membrane potential (Delta Psi m) and ROS levels. Further, dose dependent decrease in Gal-1 protein levels proves Gal-1 mediated apoptosis by 6g. Molecular docking studies were performed to understand the Gal-1 interaction with compound 6g. In addition, RP-HPLC studies showed 85.44% of 6g binding to Gal-1. Binding affinity studies by fluorescence spectroscopy and Surface Plasmon Resonance (SPR) showed that 6g binds to Gal-1 with binding constant (K-a) of 1.2 x 10(4) M-1 and equilibrium constant K-D value of 5.76 x 10(-4) M respectively.

引用

页数：15

共 46 条

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