title: Synthesis of chimeric tetrapeptide-linked cholic acid derivatives: impending synergistic agents.
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.
authors.affiliation: Organic Chemistry Synthesis Division, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, Maharashtra 411 008, India.
authors.forename: Sudhir N
authors.initials: SN
authors.lastname: Bavikar
authors.forename: Deepak B
authors.initials: DB
authors.lastname: Salunke
authors.forename: Braja G
authors.initials: BG
authors.lastname: Hazra
authors.forename: Vandana S
authors.initials: VS
authors.lastname: Pore
authors.forename: Robert H
authors.initials: RH
authors.lastname: Dodd
authors.forename: Josiane
authors.initials: J
authors.lastname: Thierry
authors.forename: Fazal
authors.initials: F
authors.lastname: Shirazi
authors.forename: Mukund V
authors.initials: MV
authors.lastname: Deshpande
authors.forename: Sreenath
authors.initials: S
authors.lastname: Kadreppa
authors.forename: Samit
authors.initials: S
authors.lastname: Chattopadhyay
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019826:Cholic Acid / Q000737:chemistry*; D015195:Drug Design; D004917:Erythromycin / Q000494:pharmacology; D015725:Fluconazole / Q000494:pharmacology; D005998:Glycine / Q000737:chemistry; D006801:Humans; D008956:Models, Chemical; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D011112:Polymyxin B / Q000031:analogs & derivatives / Q000494:pharmacology; D015091:beta-Alanine / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D015091:beta-Alanine; D004917:Erythromycin; D015725:Fluconazole; D019826:Cholic Acid; D011112:Polymyxin B; D005998:Glycine