Design and Synthesis of Novel Antimicrobial Agents

Breijyeh, Zeinab

doi:10.3390/antibiotics12030628

Cited by 31 publications

(17 citation statements)

References 281 publications

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“…Microbial contamination poses a significant threat to the food and healthcare industries, with potential direct impacts on people’s health [ 1 , 2 ]. Thus, it is imperative to prioritize the development of novel antibacterial agents that can effectively prevent bacterial growth [ 3 ]. Although antibiotics have shown success in many cases, the overuse of these drugs and the inability of conventional therapies to eradicate bacterial infections have given rise to an escalating threat of antibiotic resistance among bacterial populations [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Peptide Conjugated on Graphene Oxide-Containing Sulfonated Polyetheretherketone Substrate for Effective Antibacterial Activities against Staphylococcus aureus

Kumar,

Hu,

et al. 2023

Antibiotics

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In the present study, the antimicrobial peptide nisin was successfully conjugated onto the surface of sulfonated polyetheretherketone (SPEEK), which was decorated with graphene oxide (GO) to investigate its biofilm resistance and antibacterial properties. The PEEK was activated with sulfuric acid, resulting in a porous structure. The GO deposition fully covered the porous SPEEK specimen. The nisin conjugation was accomplished using the crosslinker 1–ethyl–3–(3–dimethylaminopropyl)carbodiimide (EDC) through a dip-coating method. The surface micrographs of the SPEEK-GO-nisin sample indicated that nisin formed discrete islets on the flat GO surface, allowing both the GO and nisin to perform a bactericidal effect. The developed materials were tested for bactericidal efficacy against Staphylococcus aureus (S. aureus). The SPEEK-GO-nisin sample had the highest antibacterial activity with an inhibition zone diameter of 27 mm, which was larger than those of the SPEEK-nisin (19 mm) and SPEEK-GO (10 mm) samples. Conversely, no inhibitory zone was observed for the PEEK and SPEEK samples. The surface micrographs of the bacteria-loaded SPEEK-GO-nisin sample demonstrated no bacterial adhesion and no biofilm formation. The SPEEK-nisin and SPEEK-GO samples showed some bacterial attachment, whereas the pure PEEK and SPEEK samples had abundant bacterial colonies and thick biofilm formation. These results confirmed the good biofilm resistance and antibacterial efficacy of the SPEEK-GO-nisin sample, which is promising for implantable orthopedic applications.

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Section: Introductionmentioning

confidence: 99%

Antimicrobial Peptide Conjugated on Graphene Oxide-Containing Sulfonated Polyetheretherketone Substrate for Effective Antibacterial Activities against Staphylococcus aureus

Kumar,

Hu,

et al. 2023

Antibiotics

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Section: Discussionmentioning

confidence: 99%

“…Small molecule antimicrobials (SMAs) present a new and effective approach to developing therapeutics, offering a wide range of possibilities for drug design to combat drug-resistant infections [ 31 , 32 ]. Pseudopyronines (PAs) are a class of α-pyrone natural products, synthesized by multiple bacterial species [ 31 , 33 ]. In this study, we screened antimicrobial activity of synthesized derivatives of PAs, varying the number of carbons from 3,4 (PA1), 6,7 (PA2), and 7,8 (PA3) on C6 and C3 positions respectively.…”

Section: Discussionmentioning

confidence: 99%

Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions Incorporating Pseudopyronine Analogs

Park,

Mahida,

et al. 2023

Antibiotics

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Multi-drug-resistant (MDR) bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), pose a significant challenge in healthcare settings. Small molecule antimicrobials (SMAs) such as α-pyrones have shown promise as alternative treatments for MDR infections. However, the hydrophobic nature of many SMAs limits their solubility and efficacy in complex biological environments. In this study, we encapsulated pseudopyronine analogs (PAs) in biodegradable polymer nanoemulsions (BNEs) for efficient eradication of biofilms. We evaluated a series of PAs with varied alkyl chain lengths and examined their antimicrobial activity against Gram-positive pathogens (S. aureus, MRSA, and B. subtilis). The selected PA with the most potent antibiofilm activity was incorporated into BNEs for enhanced solubility and penetration into the EPS matrix (PA-BNEs). The antimicrobial efficacy of PA-BNEs was assessed against biofilms of Gram-positive strains. The BNEs facilitated the solubilization and effective delivery of the PA deep into the biofilm matrix, addressing the limitations of hydrophobic SMAs. Our findings demonstrated that the PA2 exhibited synergistic antibiofilm activity when it was loaded into nanoemulsions. This study presents a promising platform for addressing MDR infections by combining pseudopyronine analogs with antimicrobial biodegradable nanoemulsions, overcoming challenges associated with treating biofilm infections.

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“…The World Health Organization (WHO) estimates that there are 700,000 casualties per year worldwide due to drug-resistant infections with a projection of 10 million deaths by 2050 and a general cost for the global economy up to USD 100 trillion. Unfortunately, the WHO also noted that in 2020, none of the 43 antibiotics in clinical use had fully solved the problem of drug resistance [ 1 ]. In this regard, the bacteria included in the ESKAPE group ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumonia , Acinetobacter baumannii , Pseudomonas aeruginosa , Enterobacter species) have been recognized by the Infectious Diseases Society of America (IDSA) as the most dangerous pathogens, due to their remarkable resistance to the most common conventional antibiotics.…”

Section: Introductionmentioning

confidence: 99%

New Pyrazolyl Thioureas Active against the Staphylococcus Genus

Schito,

Caviglia,

Penco

et al. 2024

Pharmaceuticals

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To meet the urgent need for new antibacterial molecules, a small library of pyrazolyl thioureas (PTUs) was designed, synthesized and tested against difficult-to-treat human pathogens. The prepared derivatives are characterized by a carboxyethyl functionality on C4 and different hydroxyalkyl chains on N1. Compounds 1a–o were first evaluated against a large panel of Gram-positive and Gram-negative pathogens. In particular, the majority of PTUs proved to be active against different species of the Staphylococcus genus, with MIC values ranging from 32 to 128 µg/mL on methicillin-resistant Staphylococcus strains, often responsible for severe pulmonary disease in cystic fibrosis patients. Time-killing experiments were also performed for the most active compounds, evidencing a bacteriostatic mechanism of action. For most active derivatives, cytotoxicity was evaluated in Vero cells, and at the tested concentrations and at the experimental exposure time of 24 h, none of the compounds analysed showed significant toxicity. In addition, favourable drug-like, pharmacokinetic and toxicity properties were predicted for all new synthesized derivatives. Overall, the collected data confirmed the PTU scaffold as a promising chemotype for the development of novel antibacterial agents active against Gram-positive multi-resistant strains frequently isolated from cystic fibrosis patients.

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Design and Synthesis of Novel Antimicrobial Agents

Cited by 31 publications

References 281 publications

Antimicrobial Peptide Conjugated on Graphene Oxide-Containing Sulfonated Polyetheretherketone Substrate for Effective Antibacterial Activities against Staphylococcus aureus

Antimicrobial Peptide Conjugated on Graphene Oxide-Containing Sulfonated Polyetheretherketone Substrate for Effective Antibacterial Activities against Staphylococcus aureus

Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions Incorporating Pseudopyronine Analogs

New Pyrazolyl Thioureas Active against the Staphylococcus Genus

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