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Antibiotics
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What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple...
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What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities?

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics of Drugs".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 37436

Special Issue Editor

Prof. Dr. Maria Stefania Sinicropi

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Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata, Italy
Interests: the study of new molecules as anticancer drugs; the design, synthesis and biological evaluation of compounds of pharmaceutic interest; the study and biological evaluation of nutraceuticals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the success of the discovery of ever new antimicrobials and advances in the techniques for their production, infectious diseases still remain the second leading cause of death worldwide. Self-medication and overuse of these drugs are important factors that contribute to antimicrobial resistance, leading to the constant need for research and development of new antibiotics. Today, an important goal is the discovery of new antibacterials endowed, as well, with other biological activities for high incidence diseases. For this reason, many efforts have been made in the study and biological evaluation of new natural and synthetic compounds, showing antibacterial activity along with other activities, such as antitumoral, antiviral, anti-inflammatory and so on. Conversely, molecules with different biological activities have also been demonstrated to be promising antibiotics.

This Special Issue, entitled “What’s new: Natural and synthetic antibacterials and/or agents with multiple activities?” aims to provide an overview of the most recent and original research in this area.

Prof. Dr. Maria Stefania Sinicropi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Natural antibacterials
  • Synthetic antibacterials
  • Antitumorals
  • Antivirals
  • Antioxidants
  • Antifungals
  • Anti-inflammatory

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Published Papers (9 papers)

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Research

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13 pages, 3782 KiB  
Article
Monensin, an Antibiotic Isolated from Streptomyces Cinnamonensis, Regulates Human Neuroblastoma Cell Proliferation via the PI3K/AKT Signaling Pathway and Acts Synergistically with Rapamycin
by Sema Serter Kocoglu, Mücahit Secme, Ceren Oy, Gözde Korkusuz and Levent Elmas
Antibiotics 2023, 12(3), 546; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics12030546 - 09 Mar 2023
Cited by 4 | Viewed by 1712
Abstract
Neuroblastoma is the most common extracranial childhood tumor and accounts for approximately 15% of pediatric cancer-related deaths. Further studies are needed to identify potential therapeutic targets for neuroblastoma. Monensin is an ionophore antibiotic obtained from Streptomyces cinnamonensis with known antibacterial and antiparasitic effects. [...] Read more.
Neuroblastoma is the most common extracranial childhood tumor and accounts for approximately 15% of pediatric cancer-related deaths. Further studies are needed to identify potential therapeutic targets for neuroblastoma. Monensin is an ionophore antibiotic obtained from Streptomyces cinnamonensis with known antibacterial and antiparasitic effects. No study has reported the effects of monensin on SH-SY5Y neuroblastoma cells by targeting the PI3K/AKT signaling pathway. The aim of this study was to investigate the antiproliferative effects of monensin alone and in combination with rapamycin in human SH-SY5Y neuroblastoma cells mediated by the PI3K/AKT signaling pathway. The effects of single and combination applications of monensin and rapamycin on SH-SY5Y cell proliferation were investigated by XTT, and their effects on the PI3K/AKT signaling pathway by RT-PCR, immunohistochemistry, immunofluorescence, and Western blotting. The combined effects of monensin and rapamycin on SH-SY5Y proliferation were most potent at 72 h (combination index < 1). The combination of monensin and rapamycin caused a significant decrease in the expression of P21RAS, AKT, and MAPK1 genes. Single and combined administrations of monensin and rapamycin caused a significant decrease in PI3K/AKT expression. Our results showed for the first time that monensin exerts an antiproliferative effect by targeting the PI3K/AKT signaling pathway in neuroblastoma cells. It is suggested that monensin and its combination with rapamycin may be an effective therapeutic candidate for treating neuroblastoma. Full article
(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities?)
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21 pages, 1334 KiB  
Article
Determination of the Relationships between the Chemical Structure and Antimicrobial Activity of a GAPDH-Related Fish Antimicrobial Peptide and Analogs Thereof
by Samuel Cashman-Kadri, Patrick Lagüe, Ismail Fliss and Lucie Beaulieu
Antibiotics 2022, 11(3), 297; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030297 - 23 Feb 2022
Cited by 5 | Viewed by 2000
Abstract
The structure–activity relationships and mode of action of synthesized glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-related antimicrobial peptides were investigated. Including the native skipjack tuna GAPDH-related peptide (SJGAP) of 32 amino acid residues (model for the study), 8 different peptide analogs were designed and synthesized to study [...] Read more.
The structure–activity relationships and mode of action of synthesized glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-related antimicrobial peptides were investigated. Including the native skipjack tuna GAPDH-related peptide (SJGAP) of 32 amino acid residues (model for the study), 8 different peptide analogs were designed and synthesized to study the impact of net charge, hydrophobicity, amphipathicity, and secondary structure on both antibacterial and antifungal activities. A net positive charge increase, by the substitution of anionic residues or C-terminal amidation, improved the antimicrobial activity of the SJGAP analogs (minimal inhibitory concentrations of 16–64 μg/mL), whereas the alpha helix content, as determined by circular dichroism, did not have a very definite impact. The hydrophobicity of the peptides was also found to be important, especially for the improvement of antifungal activity. Membrane permeabilization assays showed that the active peptides induced significant cytoplasmic membrane permeabilization in the bacteria and yeast tested, but that this permeabilization did not cause leakage of 260 nm-absorbing intracellular material. This points to a mixed mode of action involving both membrane pore formation and targeting of intracellular components. This study is the first to highlight the links between the physicochemical properties, secondary structure, antimicrobial activity, and mechanism of action of antimicrobial peptides from scombrids or homologous to GAPDH. Full article
(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities?)
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10 pages, 1245 KiB  
Article
Bis-Thiourea Quaternary Ammonium Salts as Potential Agents against Bacterial Strains from Food and Environmental Matrices
by Maria Grazia Bonomo, Teresa Giura, Giovanni Salzano, Pasquale Longo, Annaluisa Mariconda, Alessia Catalano, Domenico Iacopetta, Jessica Ceramella, Maria Stefania Sinicropi and Carmela Saturnino
Antibiotics 2021, 10(12), 1466; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10121466 - 28 Nov 2021
Cited by 6 | Viewed by 1844
Abstract
In recent years, the phenomenon of antibiotic resistance in hospitals, communities and the environment has increasingly grown, so antibiotic resistance has become an urgent problem that requires a decisive and global intervention. Incorrect/unnecessary use of antibiotics contributes to increase the ability of microorganisms [...] Read more.
In recent years, the phenomenon of antibiotic resistance in hospitals, communities and the environment has increasingly grown, so antibiotic resistance has become an urgent problem that requires a decisive and global intervention. Incorrect/unnecessary use of antibiotics contributes to increase the ability of microorganisms to develop resistance faster and faster. Research efforts must, therefore, be made to ensure a future in which antibiotic drugs will still be useful in combating infectious diseases. The search for new antibacterial compounds is fundamental. In this study, the antimicrobial activity of the compounds was evaluated against selected bacterial strains from food and environmental matrices by using the Agar Well Diffusion Assay. A total of thirty-six Gram-positive and Gram-negative bacteria were employed to determine the action spectrum and the antimicrobial effectiveness of a small series of thiourea derivatives. Results showed that the highest activities were found for compounds 1 and 4. The important role of the alkyl chain length and/or guanidine moiety in the width of action spectrum was evidenced. Further studies will allow evaluating the efficacy of the inhibiting action and the molecular mechanisms underlying this activity in order to identify compounds capable of counteracting the phenomenon of antibiotic resistance and to identify possible future applications of these newly synthesized compounds that have shown a high bactericidal action potential. Full article
(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities?)
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22 pages, 21309 KiB  
Article
Antibacterial, Immunomodulatory, and Lung Protective Effects of Boswelliadalzielii Oleoresin Ethanol Extract in Pulmonary Diseases: In Vitro and In Vivo Studies
by Badriyah Alotaibi, Walaa A. Negm, Engy Elekhnawy, Thanaa A. El-Masry, Walaa S. Elseady, Asmaa Saleh, Khalid N. Alotaibi and Suzy A. El-Sherbeni
Antibiotics 2021, 10(12), 1444; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10121444 - 25 Nov 2021
Cited by 31 | Viewed by 3287
Abstract
Lung diseases such as asthma, chronic obstructive pulmonary diseases, and pneumonia are causing many global health problems. The COVID-19 pandemic has directed the scientific community’s attention toward performing more research to explore novel therapeutic drugs for pulmonary diseases. Herein, gas chromatography coupled with [...] Read more.
Lung diseases such as asthma, chronic obstructive pulmonary diseases, and pneumonia are causing many global health problems. The COVID-19 pandemic has directed the scientific community’s attention toward performing more research to explore novel therapeutic drugs for pulmonary diseases. Herein, gas chromatography coupled with mass spectrometry tentatively identified 44 compounds in frankincense ethanol extract (FEE). We investigated the antibacterial and antibiofilm effects of FEE against Pseudomonas aeruginosa bacteria, isolated from patients with respiratory infections. In addition, its in vitro immunomodulatory activity was explored by the detection of the gene expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide synthase (iNOS), cycloxygenase-2 (COX-2), and nuclear factor kappa-B (NF-κB) in lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells (PBMC). In addition, its anticancer activity against the A549 lung cancer cell line and human skin fibroblast (HSF) normal cell line was studied. Moreover, the in vivo lung protective potential of FEE was explored histologically and immunohistochemically in mice using a benzo(a)pyrene induced lung damage model. FEE exhibited antibacterial and antibiofilm activities besides the significant inhibition of gene expression of TNFα, IL-6, and NF-κB. FEE also exerted a cytotoxic effect against A549 cell line. Histological and immunohistochemical investigations with morphometric analysis of the mean area percentage and color intensity of positive TNF-α, COX-2, and NF-κB and Bcl-2 reactions revealed the lung protective activity of FEE. This study outlined the promising therapeutic activity of oleoresin obtained from B. dalzielii in the treatment of different pulmonary diseases. Full article
(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities?)
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27 pages, 5950 KiB  
Article
In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes
by Alberto Aragón-Muriel, Yamil Liscano, Yulieth Upegui, Sara M. Robledo, María Teresa Ramírez-Apan, David Morales-Morales, Jose Oñate-Garzón and Dorian Polo-Cerón
Antibiotics 2021, 10(6), 728; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060728 - 16 Jun 2021
Cited by 33 | Viewed by 4301
Abstract
Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1 [...] Read more.
Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1H-benzimidazol-2-yl)aniline, salicylaldehyde, and 2,4-dihydroxybenzaldehyde were synthesized and characterized using different spectroscopic methods. Besides their cytotoxic activities, they were examined in human U-937 cells, primate kidney non-cancerous COS-7, and six other, different human tumor cell lines: U251, PC-3, K562, HCT-15, MCF-7, and SK-LU-1. In addition, the synthesized compounds were screened for in vitro antiparasitic activity against Leishmania braziliensis, Plasmodium falciparum, and Trypanosoma cruzi. Additionally, antibacterial activities were examined against two Gram-positive strains (S. aureus ATCC® 25923, L. monocytogenes ATCC® 19115) and two Gram-negative strains (E. coli ATCC® 25922, P. aeruginosa ATCC® 27583) using the microdilution method. The lanthanide complexes generally exhibited increased biological activity compared with the free Schiff base ligands. Interactions between the tested compounds and model membranes were examined using differential scanning calorimetry (DSC), and interactions with calf thymus DNA (CT-DNA) were investigated by ultraviolet (UV) absorption. Molecular docking studies were performed using leishmanin (1LML), cruzain (4PI3), P. falciparum alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and S.aureus penicillin-binding protein 2a (PBP2A; 5M18) as the protein receptors. The results lead to the conclusion that the synthesized compounds exhibited a notable effect on model membranes imitating mammalian and bacterial membranes and rolled along DNA strands through groove interactions. Interactions between the compounds and studied receptors depended primarily on ligand structures in the molecular docking study. Full article
(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities?)
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21 pages, 2714 KiB  
Article
Antibacterial Potential by Rupture Membrane and Antioxidant Capacity of Purified Phenolic Fractions of Persea americana Leaf Extract
by Laura María Solís-Salas, Crystel Aleyvick Sierra-Rivera, Luis Enrique Cobos-Puc, Juan Alberto Ascacio-Valdés and Sonia Yesenia Silva-Belmares
Antibiotics 2021, 10(5), 508; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10050508 - 29 Apr 2021
Cited by 10 | Viewed by 2480
Abstract
The present research focused on evaluating the antibacterial effect and the mechanism of action of partially purified fractions of an extract of Persea americana. Furthermore, both its antioxidant capacity and composition were evaluated. The extract was fractionated by vacuum liquid chromatography. The [...] Read more.
The present research focused on evaluating the antibacterial effect and the mechanism of action of partially purified fractions of an extract of Persea americana. Furthermore, both its antioxidant capacity and composition were evaluated. The extract was fractionated by vacuum liquid chromatography. The antimicrobial effect against Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 11229), Pseudomonas aeruginosa (ATCC 15442), and Salmonella choleraesuis (ATCC 1070) was analyzed by microdilution and the mechanism of action by the Sytox green method. The antioxidant capacity was determined by DPPH, FRAP, and ABTS techniques and the composition by Rp-HPLC-MS. All fractions showed a concentration-dependent antibacterial effect. Fractions F3, F4, and F5 (1000 µg/mL) showed a better antibacterial effect than the extract against the bacteria mentioned. The F3 fraction showed inhibition of 95.43 ± 3.04% on S. aureus, F4 showed 93.30 ± 0.52% on E. coli, and F5 showed 88.63 ± 1.15% on S. choleraesuis and 86.46 ± 3.20% on P. aeruginosa. The most susceptible strain to the treatment with the extract was S. aureus. Therefore, in this strain, the bacterial membrane damage induced by the extract and fractions was evidenced by light fluorescence microscopy. Furthermore, the extract had better antioxidant action than each fraction. Finally, sinensitin was detected in F3 and cinnamoyl glucose, caffeoyl tartaric acid, and cyanidin 3-O-(6′′-malonyl-3′′-glucosyl-glucoside) were detected in F4; esculin and kaempferide, detected in F5, could be associated with the antibacterial and antioxidant effect. Full article
(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities?)
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13 pages, 921 KiB  
Article
Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban
by Alessia Catalano, Domenico Iacopetta, Antonio Rosato, Lara Salvagno, Jessica Ceramella, Francesca Longo, Maria Stefania Sinicropi and Carlo Franchini
Antibiotics 2021, 10(2), 204; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10020204 - 19 Feb 2021
Cited by 12 | Viewed by 2519
Abstract
Triclocarban (TCC), a broad-spectrum lipophilic antimicrobial agent, is a diarylurea derivative that has been used for more than 60 years as a major ingredient of toys, clothing, food packaging materials, food industry floors, medical supplies and especially of personal care products, such as [...] Read more.
Triclocarban (TCC), a broad-spectrum lipophilic antimicrobial agent, is a diarylurea derivative that has been used for more than 60 years as a major ingredient of toys, clothing, food packaging materials, food industry floors, medical supplies and especially of personal care products, such as soaps, toothpaste and shampoo. In September 2016, the U.S. FDA banned nineteen antimicrobial ingredients, including TCC, in over-the-counter consumer antiseptic wash products, due to their toxicity. Withdrawal of TCC has prompted efforts to search for new antimicrobial compounds. In this paper, we present the synthesis and biological evaluation, as antibiotic and non-cytotoxic agents, of a series of diarylureas, analogues of TCC. These compounds are characterized by an intriguingly simple chemistry and can be easily synthesized. Among the synthesized compounds, 1ab and 1bc emerge as the most interesting compounds as they show the same activity of TCC (MIC = 16 µg/mL) against Staphylococcus aureus, and a higher activity than TCC against Enterococcus faecalis (MIC = 32 µg/mL versus MIC = 64 µg/mL). Moreover, 1ab and 1bc show no cytotoxicity towards the human mammary epithelial cells MCF-10A and embryonic kidney epithelial cells Hek-293, in opposition to TCC, which exhibits a marked cytotoxicity on the same cell lines and shows a good antitumor activity on a panel of cell lines tested. Full article
(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities?)
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Review

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58 pages, 23244 KiB  
Review
Molecular Insights into Coumarin Analogues as Antimicrobial Agents: Recent Developments in Drug Discovery
by Rameshwar S. Cheke, Harun M. Patel, Vaishali M. Patil, Iqrar Ahmad Ansari, Jaya P. Ambhore, Sachin D. Shinde, Adel Kadri, Mejdi Snoussi, Mohd Adnan, Prashant S. Kharkar, Visweswara Rao Pasupuleti and Prashant K. Deshmukh
Antibiotics 2022, 11(5), 566; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11050566 - 24 Apr 2022
Cited by 30 | Viewed by 4077
Abstract
A major global health risk has been witnessed with the development of drug-resistant bacteria and multidrug-resistant pathogens linked to significant mortality. Coumarins are heterocyclic compounds belonging to the benzophenone class enriched in different plants. Coumarins and their derivatives have a wide range of [...] Read more.
A major global health risk has been witnessed with the development of drug-resistant bacteria and multidrug-resistant pathogens linked to significant mortality. Coumarins are heterocyclic compounds belonging to the benzophenone class enriched in different plants. Coumarins and their derivatives have a wide range of biological activity, including antibacterial, anticoagulant, antioxidant, anti-inflammatory, antiviral, antitumour, and enzyme inhibitory effects. In the past few years, attempts have been reported towards the optimization, synthesis, and evaluation of novel coumarin analogues as antimicrobial agents. Several coumarin-based antibiotic hybrids have been developed, and the majority of them were reported to exhibit potential antibacterial effects. In the present work, studies reported from 2016 to 2020 about antimicrobial coumarin analogues are the focus. The diverse biological spectrum of coumarins can be attributed to their free radical scavenging abilities. In addition to various synthetic strategies developed, some of the structural features include a heterocyclic ring with electron-withdrawing/donating groups conjugated with the coumarin nucleus. The suggested structure−activity relationship (SAR) can provide insight into how coumarin hybrids can be rationally improved against multidrug-resistant bacteria. The present work demonstrates molecular insights for coumarin derivatives having antimicrobial properties from the recent past. The detailed SAR outcomes will benefit towards leading optimization during the discovery and development of novel antimicrobial therapeutics. Full article
(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities?)
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55 pages, 3211 KiB  
Review
Applications of Lysozyme, an Innate Immune Defense Factor, as an Alternative Antibiotic
by Patrizia Ferraboschi, Samuele Ciceri and Paride Grisenti
Antibiotics 2021, 10(12), 1534; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10121534 - 14 Dec 2021
Cited by 116 | Viewed by 13649
Abstract
Lysozyme is a ~14 kDa protein present in many mucosal secretions (tears, saliva, and mucus) and tissues of animals and plants, and plays an important role in the innate immunity, providing protection against bacteria, viruses, and fungi. Three main different types of lysozymes [...] Read more.
Lysozyme is a ~14 kDa protein present in many mucosal secretions (tears, saliva, and mucus) and tissues of animals and plants, and plays an important role in the innate immunity, providing protection against bacteria, viruses, and fungi. Three main different types of lysozymes are known: the c-type (chicken or conventional type), the g-type (goose type), and the i-type (invertebrate type). It has long been the subject of several applications due to its antimicrobial properties. The problem of antibiotic resistance has stimulated the search for new molecules or new applications of known compounds. The use of lysozyme as an alternative antibiotic is the subject of this review, which covers the results published over the past two decades. This review is focused on the applications of lysozyme in medicine, (the treatment of infectious diseases, wound healing, and anti-biofilm), veterinary, feed, food preservation, and crop protection. It is available from a wide range of sources, in addition to the well-known chicken egg white, and its synergism with other compounds, endowed with antimicrobial activity, are also summarized. An overview of the modified lysozyme applications is provided in the form of tables. Full article
(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities?)
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