2. Academic Validation
  3. Synthesis, Structure-Activity Relationship, and Mechanistic Investigation of Lithocholic Acid Amphiphiles for Colon Cancer Therapy

Synthesis, Structure-Activity Relationship, and Mechanistic Investigation of Lithocholic Acid Amphiphiles for Colon Cancer Therapy

  • Medchemcomm. 2015 Jan;6(1):192-201. doi: 10.1039/C4MD00223G.
Manish Singh # 1,  Sandhya Bansal # 1,  Somanath Kundu # 1 2,  Priyanshu Bhargava 1,  Ashima Singh 1,  Rajender K Motiani 1,  Radhey Shyam 3,  Vedagopuram Sreekanth 1 2,  Sagar Sengupta 3,  Avinash Bajaj 1
Affiliations

Affiliations

  • 1 The Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, 180 Udyog Vihar, Phase 1, Gurgaon-122016, Haryana, India.
  • 2 Manipal University, Manipal, Karnatka, India.
  • 3 National Institute of Immunology, Aruna Asif Ali Marg, New Delhi 110067, India.
  • # Contributed equally.
PMID: 25685308 DOI: 10.1039/C4MD00223G
Abstract

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 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 charged head group. Lithocholic acid based amphiphile possessing piperidine head group (LCA-PIP1 ) is ~10 times more cytotoxic as compared to its precursor. Biochemical studies revealed that enhanced activity of LCA-PIP1 as compared to lithocholic acid is due to greater activation of Apoptosis.LCA-PIP1 induces sub G0 arrest and causes cleavage of caspases. A single dose of lithocholic acid-piperidine derivative is enough to reduce the tumor burden by 75% in tumor xenograft model.

Keywords

Amphiphiles; Anticancer activities; Bile acids; Cancer; Colon Cancer.

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