Bioorganic & Medicinal Chemistry Letters 2008-10-15

Synthesis of chimeric tetrapeptide-linked cholic acid derivatives: impending synergistic agents.

Sudhir N Bavikar, Deepak B Salunke, Braja G Hazra, Vandana S Pore, Robert H Dodd, Josiane Thierry, Fazal Shirazi, Mukund V Deshpande, Sreenath Kadreppa, Samit Chattopadhyay

Index: Bioorg. Med. Chem. Lett. 18 , 5512-7, (2008)

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Abstract

Tetrapeptides derived from glycine and beta-alanine were hooked at the C-3beta position of the modified cholic acid to realize novel linear tetrapeptide-linked cholic acid derivatives. All the synthesized compounds were tested against a wide variety of microorganisms (gram-negative bacteria, gram-positive bacteria and fungi) and their cytotoxicity was evaluated against human embryonic kidney (HEK293) and human mammary adenocarcinoma (MCF-7) cell lines. While relatively inactive by themselves, these compounds interact synergistically with antibiotics such as fluconazole and erythromycin to inhibit growth of fungi and bacteria, respectively, at 1-24 microg/mL. The synergistic effect shown by our novel compounds is due to their inherent amphiphilicity. The fractional inhibitory concentrations reported are comparable to those reported for Polymyxin B derivatives.