Effect of the Nature of the Spacer on Gene Transfer Efficacies of Novel Thiocholesterol Derived Gemini Lipids in Different Cell Lines: A Structure–Activity Investigation

Avinash Bajaj†, Paturu Kondaiah‡ and Santanu Bhattacharya*†§
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India, Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560 012, India, and Chemical Biology Unit of JNCASR, Bangalore 560 064, India
J. Med. Chem., 2008, 51 (8), pp 2533–2540
DOI: 10.1021/jm7010436
Publication Date (Web): April 1, 2008
Copyright © 2008 American Chemical Society
†

Department of Organic Chemistry, Indian Institute of Science.

,
‡

Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science.

,
* To whom correspondence should be addressed. Phone: (91)-80-2293-2664 . Fax: (91)-80-2360-0529. E-mail: sb@orgchem.iisc.ernet.in.
,
§

Chemical Biology Unit of JNCASR.

Abstract

Abstract Image

A structure–activity investigation was undertaken to see the effect of the nature of the spacer on the gene transfection efficacies of thiocholesterol-derived cationic gemini lipids possessing disulfide linkage between the cationic headgroup and the thiocholesterol moiety. Three gemini cationic lipids possessing hydrophobic flexible (-(CH2)5-; 1), hydrophobic rigid (-C6H4-; 2), and hydrophilic flexible (-CH2-CH2-O-CH2-CH2-; 3) spacer segments were synthesized. In HeLa cells, lipid formulations 1 and 2 were found to be more effective as compared to lipid 3 formulation. In HT1080 cell line, the order of transfectability was 3 > 1 > 2. Transfection studies in HeLa and HT1080 cell line also showed 40–50% transfection efficacy in the presence of 10% serum conditions. These formulations were also able to transfect gene across difficult cells like HaCaT. Cytotoxic studies showed the nontoxic nature of these lipid−DNA complexes at different N/P ratios used for transfection studies.

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History

  • Published In Issue April 24, 2008
  • Article ASAPApril 01, 2008
  • Received: August 22, 2007

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