Synthesis, structure-activity relationship, and mechanistic investigation of lithocholic acid amphiphiles for colon cancer therapy

被引：1

作者：

Singh, Manish ^{[1
]}

Bansal, Sandhya ^{[1
]}

Kundu, Somanath ^{[1
,3
]}

Bhargava, Priyanshu ^{[1
]}

Singh, Ashima ^{[1
]}

Motiani, Rajender K. ^{[1
]}

Shyam, Radhey ^{[2
]}

Sreekanth, Vedagopuram ^{[1
,3
]}

Sengupta, Sagar ^{[2
]}

Bajaj, Avinash ^{[1
]}

机构：

[1] Reg Ctr Biotechnol, Lab Nanotechnol & Chem Biol, Gurgaon 122016, Haryana, India

[2] Natl Inst Immunol, New Delhi 110067, India

[3] Manipal Univ, Manipal, Karnataka, India

来源：

MEDCHEMCOMM | 2015年 / 6卷 / 01期

关键词：

BILE-ACIDS; INDUCED APOPTOSIS; COLORECTAL-CANCER; CELLULAR UPTAKE; CHOLIC-ACID; HYDROPHOBICITY; AGENTS; DERIVATIVES; DESIGN; CELLS;

D O I：

10.1039/c4md00223g

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：

We report a structure-activity relationship of lithocholic acid amphiphiles for their anticancer activities against colon cancer. We synthesized ten cationic amphiphiles, differing in nature of their cationic charged head groups, using lithocholic acid. We observed that anticancer activities of these amphiphiles against colon cancer cell lines are contingent on nature of the charged head group. The lithocholic acid-based amphiphile possessing a piperidine head group (LCA-PIP1) is similar to 10 times more cytotoxic than its precursor. Biochemical studies revealed that enhanced activity of LCA-PIP1 compared to lithocholic acid is due to a greater activation of apoptosis. LCA-PIP1 induces sub G(0) arrest and causes cleavage of caspases. A single dose of lithocholic acid-piperidine (LCA-PIP1) derivative is enough to reduce the tumor burden by 75% in a tumor xenograft model.

引用

页码：192 / 201

页数：10

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