A novel dodecapeptide from a combinatorial synthetic library exhibits potent antifungal activity and synergy with standard antimycotic agents.
There has been a marked expansion in the discovery of new antifungal peptides. This paper describes a novel dodecapeptide, H-Arg-Trp-Trp-Arg-D-Trp-D-Phe-Ile-D-Phe-His-Trp-Arg-Trp-NH(2), derived from a previously described nonapeptide and synthesized by the combinatorial approach. Further, interaction of this peptide with antifungals such as amphotericin B, flucytosine and fluconazole was studied by checkerboard analysis and time-kill assay to obtain the dynamic picture with respect to time. The best synergistic activity was observed with a combination of peptide and fluconazole, followed by peptide and flucytosine.
Duggineni
S
S
Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow-226 001, India.
Srivastava
G
G
Kundu
B
B
Kumar
M
M
Chaturvedi
A K
AK
Shukla
P K
PK
D000595:Amino Acid Sequence; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D003455:Cryptococcus neoformans / Q000187:drug effects; D004357:Drug Synergism; D004912:Erythrocytes / Q000187:drug effects; D015725:Fluconazole / Q000494:pharmacology; D005437:Flucytosine / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits
D000935:Antifungal Agents; D009842:Oligopeptides; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine