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Special Issue "Focus on Antibiotics – New Challenges and Steps Forward in Discovery and Development (Volume II)"

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 30 September 2023 | Viewed by 3943

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Prof. Dr. Aura Rusu

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Pharmaceutical and Therapeutical Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 38 Gheorghe Marinescu Street, 540142 Targu Mureș, Romania
Interests: pharmaceutical chemistry; medicinal chemistry; drug design; antibacterial agents; metal complexes; drug analysis; capillary electrophoresis; patient–pharmacist communication
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Prof. Dr. Valentina Uivarosi

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General and Inorganic Chemistry Department, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, Sector 2, 020956 Bucharest, Romania
Interests: design of new metal complexes with biological activity (e.g., antibacterial, anticancer, and antidiabetic activity); synthesis; characterization; DNA binding and protein interaction studies; cytotoxicity studies; drug repositioning
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The design of new antibiotics is still considered the primary weapon in the fight against the growing bacterial resistance to known antibiotics. Pharmaceutical research is focused on new approaches that lead to new successful compounds more quickly. Continuous discoveries about the structure–activity relationship in the different antibiotic classes and advances in computer-aided drug design (CADD) methods will contribute to the coming new generations of antibiotics. A new trend targets old antibiotics and other compounds from various therapeutic classes for optimization and repositioning. Additionally, hybrid drugs incorporating two active compounds into a single molecule could expand antibacterial activity and prevent bacterial resistance. Different metal complexes in antibiotics and other organic substances have already shown their potential for antibacterial activity. Nanoparticles (e.g., silver nanoparticles) are very attractive for use in multiple medical applications. Thus, in the last decade, there has been the desire to find new classes of antibiotics. New compounds with antibacterial activity are in various research stages: proteic compounds, siderophores, quinoxolidinones, natural antibiotics, antibiotic resistance breakers, and others. The second volume of this Special Issue volume II aims to highlight the recent steps toward discovering new antibiotics.

Prof. Dr. Aura Rusu
Prof. Dr. Valentina Uivarosi
Guest Editors

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Keywords

antibiotics
hybrid antibiotics
metal complexes
nanoparticles
silver nanoparticles
natural antibiotics
bioactive compounds
drug repurposing
drug repositioning
antibiotic resistance breakers
antibacterial drug resistance
antibiotic resistance

Related Special Issue

Focus on Antibiotics – New Challenges and Steps Forward in Discovery and Development in Pharmaceutics (11 articles)

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Research

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Open AccessArticle

Synthesis, Characterization, and Docking Study of Novel Thioureidophosphonate-Incorporated Silver Nanocomposites as Potent Antibacterial Agents

Ahmed I. El-Tantawy

Elshaymaa I. Elmongy

Shimaa M. Elsaeed

Abdel Aleem H. Abdel Aleem

Reem Binsuwaidan

Wael H. Eisa

Ayah Usama Salman

Noura Elsayed Elharony

and

Nour F. Attia

Pharmaceutics 2023, 15(6), 1666; https://doi.org/10.3390/pharmaceutics15061666 - 06 Jun 2023

Viewed by 142

Abstract

Newly synthesized mono- and bis-thioureidophosphonate (MTP and BTP) analogues in eco-friendly conditions were employed as reducing/capping cores for 100, 500, and 1000 mg L⁻¹ of silver nitrate. The physicochemical properties of silver nanocomposites (MTP(BTP)/Ag NCs) were fully elucidated using spectroscopic and microscopic tools. The antibacterial activity of the nanocomposites was screened against six multidrug-resistant pathogenic strains, comparable to ampicillin and ciprofloxacin commercial drugs. The antibacterial performance of BTP was more substantial than MTP, notably with the best minimum inhibitory concentration (MIC) of 0.0781 mg/mL towards Bacillus subtilis, Salmonella typhi, and Pseudomonas aeruginosa. Among all, BTP provided the clearest zone of inhibition (ZOI) of 35 ± 1.00 mm against Salmonella typhi. After the dispersion of silver nanoparticles (AgNPs), MTP/Ag NCs offered dose-dependently distinct advantages over the same nanoparticle with BTP; a more noteworthy decline by 4098 × MIC to 0.1525 × 10⁻³ mg/mL was recorded for MTP/Ag-1000 against Pseudomonas aeruginosa over BTP/Ag-1000. Towards methicillin-resistant Staphylococcus aureus (MRSA), the as-prepared MTP(BTP)/Ag-1000 displayed superior bactericidal ability in 8 h. Because of the anionic surface of MTP(BTP)/Ag-1000, they could effectively resist MRSA (ATCC-43300) attachment, achieving higher antifouling rates of 42.2 and 34.4% at most optimum dose (5 mg/mL), respectively. The tunable surface work function between MTP and AgNPs promoted the antibiofilm activity of MTP/Ag-1000 by 1.7 fold over BTP/Ag-1000. Lastly, the molecular docking studies affirmed the eminent binding affinity of BTP over MTP—besides the improved binding energy of MTP/Ag NC by 37.8%—towards B. subtilis-2FQT protein. Overall, this study indicates the immense potential of TP/Ag NCs as promising nanoscale antibacterial candidates. Full article

(This article belongs to the Special Issue Focus on Antibiotics – New Challenges and Steps Forward in Discovery and Development (Volume II))

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Open AccessFeature PaperArticle

Synthesis of 6″-Modified Kanamycin A Derivatives and Evaluation of Their Antibacterial Properties

and

Pharmaceutics 2023, 15(4), 1177; https://doi.org/10.3390/pharmaceutics15041177 - 07 Apr 2023

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Abstract

Aminoglycosides are one of the first classes of antibiotics to have been used clinically, and they are still being used today. They have a broad spectrum of antimicrobial activity, making them effective against many different types of bacteria. Despite their long history of use, aminoglycosides are still considered promising scaffolds for the development of new antibacterial agents, particularly as bacteria continue to develop resistances to existing antibiotics. We have synthesized a series of 6″-deoxykanamycin A analogues with additional protonatable groups (amino-, guanidino or pyridinium) and tested their biological activities. For the first time we have demonstrated the ability of the tetra-N-protected-6″-O-(2,4,6-triisopropylbenzenesulfonyl)kanamycin A to interact with a weak nucleophile, pyridine, resulting in the formation of the corresponding pyridinium derivative. Introducing small diamino-substituents at the 6″-position of kanamycin A did not significantly alter the antibacterial activity of the parent antibiotic, but further modification by acylation resulted in a complete loss of the antibacterial activity. However, introducing a guanidine residue led to a compound with improved activity against S. aureus. Moreover, most of the obtained 6″-modified kanamycin A derivatives were less influenced by the resistant mechanism associated with mutations of the elongation factor G than the parent kanamycin A. This suggests that modifying the 6″-position of kanamycin A with protonatable groups is a promising direction for the further development of new antibacterial agents with reduced resistances. Full article

(This article belongs to the Special Issue Focus on Antibiotics – New Challenges and Steps Forward in Discovery and Development (Volume II))

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Open AccessArticle

Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PL^pro Protein

Natália Vitória Bitencourt

Gabriela Marinho Righetto

Ilana Lopes Baratella Cunha Camargo

Mariana Ortiz de Godoy

Rafael Victorio Carvalho Guido

Glaucius Oliva

Norival Alves Santos-Filho

and

Eduardo Maffud Cilli

Pharmaceutics 2023, 15(2), 436; https://doi.org/10.3390/pharmaceutics15020436 - 28 Jan 2023

Cited by 1 | Viewed by 814

Abstract

Recent studies have shown that the peptide [des-Cys¹¹,Lys¹²,Lys¹³-(p-BthTX-I)₂K] (p-Bth) is a p-BthTX-I analog that shows enhanced antimicrobial activity, stability and hemolytic activity, and is easy to obtain compared to the wild-type sequence. This molecule also inhibits SARS-CoV-2 viral infection in Vero cells, acting on SARS-CoV-2 PL^pro enzymatic activity. Thus, the present study aimed to assess the effects of structural modifications to p-Bth, such as dimerization, dendrimerization and chirality, on the antibacterial activity and inhibitory properties of PL^pro. The results showed that the dimerization or dendrimerization of p-Bth was essential for antibacterial activity, as the monomeric structure led to a total loss of, or significant reduction in, bacterial activities. The dimers and tetramers obtained using branched lysine proved to be prominent compounds with antibacterial activity against Gram-positive and Gram-negative bacteria. In addition, hemolysis rates were below 10% at the corresponding concentrations. Conversely, the inhibitory activity of the PL^pro of SARS-CoV-2 was similar in the monomeric, dimeric and tetrameric forms of p-Bth. Our findings indicate the importance of the dimerization and dendrimerization of this important class of antimicrobial peptides, which shows great potential for antimicrobial and antiviral drug-discovery campaigns. Full article

(This article belongs to the Special Issue Focus on Antibiotics – New Challenges and Steps Forward in Discovery and Development (Volume II))

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Open AccessArticle

Bacteriocin-Nanoconjugates (Bac10307-AgNPs) Biosynthesized from Lactobacillus acidophilus-Derived Bacteriocins Exhibit Enhanced and Promising Biological Activities

Mohammed Merae Alshahrani

Abdelmushin Abdelgadir

Fevzi Bardakci

Manojkumar Sachidanandan

Riadh Badraoui

Mejdi Snoussi

and

Allal Ouhtit

Pharmaceutics 2023, 15(2), 403; https://doi.org/10.3390/pharmaceutics15020403 - 25 Jan 2023

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Abstract

The proteinaceous compounds produced by lactic acid bacteria are called bacteriocins and have a wide variety of bioactive properties. However, bacteriocin’s commercial availability is limited due to short stability periods and low yields. Therefore, the objective of this study was to synthesize bacteriocin-derived silver nanoparticles (Bac10307-AgNPs) extracted from Lactobacillus acidophilus (L. acidophilus), which may have the potential to increase the bioactivity of bacteriocins and overcome the hurdles. It was found that extracted and purified Bac10307 had a broad range of stability for both temperature (20–100 °C) and pH (3–12). Further, based on Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS–PAGE) analysis, its molecular weight was estimated to be 4.2 kDa. The synthesized Bac10307-AgNPs showed a peak of surface plasmon resonance at 430 nm λmax. Fourier transform infrared (FTIR) confirmed the presence of biological moieties, and transmission electron microscopy (TEM) coupled with Energy dispersive X-Ray (EDX) confirmed that AgNPs were spherical and irregularly shaped, with a size range of 9–20 nm. As a result, the Bac10307-AgNPs displayed very strong antibacterial activity with MIC values as low as 8 μg/mL for Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), when compared to Bac10307 alone. In addition, Bac10307-AgNPs demonstrated promising in vitro antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC₅₀ = 116.04 μg/mL) and in vitro cytotoxicity against human liver cancer cells (HepG2) (IC₅₀ = 135.63 μg/mL), more than Bac10307 alone (IC₅₀ = 139.82 μg/mL against DPPH and 158.20 μg/mL against HepG2). Furthermore, a protein–protein molecular docking simulation study of bacteriocins with target proteins of different biological functions was also carried out in order to ascertain the interactions between bacteriocins and target proteins. Full article

(This article belongs to the Special Issue Focus on Antibiotics – New Challenges and Steps Forward in Discovery and Development (Volume II))

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Review

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Open AccessReview

Antibiotic-Loaded Gold Nanoparticles: A Nano-Arsenal against ESBL Producer-Resistant Pathogens

Syed Mohd Danish Rizvi

and

Pharmaceutics 2023, 15(2), 430; https://doi.org/10.3390/pharmaceutics15020430 - 28 Jan 2023

Viewed by 817

Abstract

The advent of new antibiotics has helped clinicians to control severe bacterial infections. Despite this, inappropriate and redundant use of antibiotics, inadequate diagnosis, and smart resistant mechanisms developed by pathogens sometimes lead to the failure of treatment strategies. The genotypic analysis of clinical samples revealed that the rapid spread of extended-spectrum β-lactamases (ESBLs) genes is one of the most common approaches acquired by bacterial pathogens to become resistant. The scenario compelled the researchers to prioritize the design and development of novel and effective therapeutic options. Nanotechnology has emerged as a plausible groundbreaking tool against resistant infectious pathogens. Numerous reports suggested that inorganic nanomaterials, specifically gold nanoparticles (AuNPs), have converted unresponsive antibiotics into potent ones against multi-drug resistant pathogenic strains. Interestingly, after almost two decades of exhaustive preclinical evaluations, AuNPs are gradually progressively moving ahead toward clinical evaluations. However, the mechanistic aspects of the antibacterial action of AuNPs remain an unsolved puzzle for the scientific fraternity. Thus, the review covers state-of-the-art investigations pertaining to the efficacy of AuNPs as a tool to overcome ESBLs acquired resistance, their applicability and toxicity perspectives, and the revelation of the most appropriate proposed mechanism of action. Conclusively, the trend suggested that antibiotic-loaded AuNPs could be developed into a promising interventional strategy to limit and overcome the concerns of antibiotic-resistance. Full article

(This article belongs to the Special Issue Focus on Antibiotics – New Challenges and Steps Forward in Discovery and Development (Volume II))

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