Back to Search
Start Over
Synthesis of Second-Generation Analogs of Temporin-SHa Peptide Having Broad-Spectrum Antibacterial and Anticancer Effects.
- Source :
- Antibiotics (2079-6382); Aug2024, Vol. 13 Issue 8, p758, 16p
- Publication Year :
- 2024
-
Abstract
- Antimicrobial peptides (AMPs) are a promising class of therapeutic alternatives with broad-spectrum activity against resistant pathogens. Small AMPs like temporin-SHa (1) and its first-generation analog [G10a]-SHa (2) possess notable efficacy against Gram-positive and Gram-negative bacteria. In an effort to further improve this antimicrobial activity, second-generation analogs of 1 were synthesised by replacing the natural glycine residue at position-10 of the parent molecule with atypical amino acids, such as D-Phenylalanine, D-Tyrosine and (2-Naphthyl)-D-alanine, to study the effect of hydrophobicity on antimicrobial efficacy. The resultant analogs (3–6) emerged as broad-spectrum antibacterial agents. Notably, the [G10K]-SHa analog (4), having a lysine substitution, demonstrated a 4-fold increase in activity against Gram-negative (Enterobacter cloacae DSM 30054) and Gram-positive (Enterococcus faecalis DSM 2570) bacteria relative to the parent peptide (1). Among all analogs, [G10f]-SHa peptide (3), featuring a D-Phe substitution, showed the most potent anticancer activity against lung cancer (A549), skin cancer (MNT-1), prostate cancer (PC-3), pancreatic cancer (MiaPaCa-2) and breast cancer (MCF-7) cells, achieving an IC<subscript>50</subscript> value in the range of 3.6–6.8 µM; however, it was also found to be cytotoxic against normal cell lines as compared to [G10K]-SHa (4). Peptide 4 also possessed good anticancer activity but was found to be less cytotoxic against normal cell lines as compared to 1 and 3. These findings underscore the potential of second-generation temporin-SHa analogs, especially analog 4, as promising leads to develop new broad-spectrum antibacterial and anticancer agents. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20796382
- Volume :
- 13
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- Antibiotics (2079-6382)
- Publication Type :
- Academic Journal
- Accession number :
- 179381306
- Full Text :
- https://doi.org/10.3390/antibiotics13080758