Synthesis of chimeric tetrapeptide-linked cholic acid derivatives: impending synergistic agents.
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.
Bavikar
Sudhir N
SN
Organic Chemistry Synthesis Division, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, Maharashtra 411 008, India.
Salunke
Deepak B
DB
Hazra
Braja G
BG
Pore
Vandana S
VS
Dodd
Robert H
RH
Thierry
Josiane
J
Shirazi
Fazal
F
Deshpande
Mukund V
MV
Kadreppa
Sreenath
S
Chattopadhyay
Samit
S
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
D000900:Anti-Bacterial Agents; D010455:Peptides; D015091:beta-Alanine; D004917:Erythromycin; D015725:Fluconazole; D019826:Cholic Acid; D011112:Polymyxin B; D005998:Glycine