Macrocyclic peptidomimetics with antimicrobial activity

synthesis, bioassay, and molecular modeling studies

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry. Microbiological testing of the synthesized compounds revealed an exceptionally high activity against Candida albicans with a minimum inhibitory concentration (MIC) two orders of magnitude lower than the MIC of the antifungal reference drug amphotericin B. A strikingly high activity was also observed against three Gram-negative bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris), two of which are known human pathogens. Thus the discovered chemotype is a potential polypharmacological agent. The toxicity against mammalian tumor cells was found to be low, as demonstrated in five different human cell lines (HeLa, cervical; PC-3, prostate; MCF-7, breast; HepG2, liver; and HCT-116, colon). The internal consistency of the experimental data was studied using 3D-pharmacophore and 2D-QSAR.

Original languageEnglish (US)
Pages (from-to)9492-503
Number of pages12
JournalOrganic and Biomolecular Chemistry
Volume13
Issue number36
DOIs
StatePublished - Sep 28 2015

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Peptidomimetics
bioassay
Molecular modeling
Bioassay
Microbial Sensitivity Tests
Biological Assay
Proteus
Cells
Klebsiella
Proteus vulgaris
pneumonia
acylation
Acylation
pseudomonas
Quantitative Structure-Activity Relationship
pathogens
Candida
Klebsiella pneumoniae
Amphotericin B
Pathogens

Keywords

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Candida albicans
  • Cell Line, Tumor
  • Cell Proliferation
  • Dose-Response Relationship, Drug
  • Gram-Negative Bacteria
  • Humans
  • Macrocyclic Compounds
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Peptidomimetics
  • Quantitative Structure-Activity Relationship
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

@article{930104cbdd8042408c7b42760ab101fb,
title = "Macrocyclic peptidomimetics with antimicrobial activity: synthesis, bioassay, and molecular modeling studies",
abstract = "Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry. Microbiological testing of the synthesized compounds revealed an exceptionally high activity against Candida albicans with a minimum inhibitory concentration (MIC) two orders of magnitude lower than the MIC of the antifungal reference drug amphotericin B. A strikingly high activity was also observed against three Gram-negative bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris), two of which are known human pathogens. Thus the discovered chemotype is a potential polypharmacological agent. The toxicity against mammalian tumor cells was found to be low, as demonstrated in five different human cell lines (HeLa, cervical; PC-3, prostate; MCF-7, breast; HepG2, liver; and HCT-116, colon). The internal consistency of the experimental data was studied using 3D-pharmacophore and 2D-QSAR.",
keywords = "Anti-Bacterial Agents, Antifungal Agents, Candida albicans, Cell Line, Tumor, Cell Proliferation, Dose-Response Relationship, Drug, Gram-Negative Bacteria, Humans, Macrocyclic Compounds, Microbial Sensitivity Tests, Models, Molecular, Molecular Structure, Peptidomimetics, Quantitative Structure-Activity Relationship, Journal Article, Research Support, Non-U.S. Gov't",
author = "Panda, {Siva S}",
year = "2015",
month = "9",
day = "28",
doi = "10.1039/c5ob01400j",
language = "English (US)",
volume = "13",
pages = "9492--503",
journal = "Organic and Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",
number = "36",

}

TY - JOUR

T1 - Macrocyclic peptidomimetics with antimicrobial activity

T2 - synthesis, bioassay, and molecular modeling studies

AU - Panda, Siva S

PY - 2015/9/28

Y1 - 2015/9/28

N2 - Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry. Microbiological testing of the synthesized compounds revealed an exceptionally high activity against Candida albicans with a minimum inhibitory concentration (MIC) two orders of magnitude lower than the MIC of the antifungal reference drug amphotericin B. A strikingly high activity was also observed against three Gram-negative bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris), two of which are known human pathogens. Thus the discovered chemotype is a potential polypharmacological agent. The toxicity against mammalian tumor cells was found to be low, as demonstrated in five different human cell lines (HeLa, cervical; PC-3, prostate; MCF-7, breast; HepG2, liver; and HCT-116, colon). The internal consistency of the experimental data was studied using 3D-pharmacophore and 2D-QSAR.

AB - Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry. Microbiological testing of the synthesized compounds revealed an exceptionally high activity against Candida albicans with a minimum inhibitory concentration (MIC) two orders of magnitude lower than the MIC of the antifungal reference drug amphotericin B. A strikingly high activity was also observed against three Gram-negative bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris), two of which are known human pathogens. Thus the discovered chemotype is a potential polypharmacological agent. The toxicity against mammalian tumor cells was found to be low, as demonstrated in five different human cell lines (HeLa, cervical; PC-3, prostate; MCF-7, breast; HepG2, liver; and HCT-116, colon). The internal consistency of the experimental data was studied using 3D-pharmacophore and 2D-QSAR.

KW - Anti-Bacterial Agents

KW - Antifungal Agents

KW - Candida albicans

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Dose-Response Relationship, Drug

KW - Gram-Negative Bacteria

KW - Humans

KW - Macrocyclic Compounds

KW - Microbial Sensitivity Tests

KW - Models, Molecular

KW - Molecular Structure

KW - Peptidomimetics

KW - Quantitative Structure-Activity Relationship

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1039/c5ob01400j

DO - 10.1039/c5ob01400j

M3 - Article

VL - 13

SP - 9492

EP - 9503

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

IS - 36

ER -