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Progress in Medicinal Chemistry 2018This chapter will discuss the recent literature of macrocycles and drug-like property space moving beyond the rule of five (bRo5). Trends in chemical classes that fall... (Review)
Review
This chapter will discuss the recent literature of macrocycles and drug-like property space moving beyond the rule of five (bRo5). Trends in chemical classes that fall within this definition are discussed and the impact of the latest technologies in the field assessed. The physicochemical properties, which have provided both successes and challenges, especially in scale-up, are discussed. A recent patent literature is reviewed and the chapter concludes with a perspective on the future of macrocyclic drug discovery.
Topics: Anti-Infective Agents; Drug Discovery; Humans; Macrocyclic Compounds; Molecular Structure; Structure-Activity Relationship
PubMed: 29680148
DOI: 10.1016/bs.pmch.2018.01.002 -
International Journal of Molecular... Apr 2023Infections that occur during wound healing involve the most frequent complications in the field of wound care which not only inhibit the whole process but also lead to... (Review)
Review
Infections that occur during wound healing involve the most frequent complications in the field of wound care which not only inhibit the whole process but also lead to non-healing wound formation. The diversity of the skin microbiota and the wound microenvironment can favor the occurrence of skin infections, contributing to an increased level of morbidity and even mortality. As a consequence, immediate effective treatment is required to prevent such pathological conditions. Antimicrobial agents loaded into wound dressings have turned out to be a great option to reduce wound colonization and improve the healing process. In this review paper, the influence of bacterial infections on the wound-healing phases and promising modifications of dressing materials for accelerated healing of infected wounds are discussed. The review paper mainly focuses on the novel findings on the use of antibiotics, nanoparticles, cationic organic agents, and plant-derived natural compounds (essential oils and their components, polyphenols, and curcumin) to develop antimicrobial wound dressings. The review article was prepared on the basis of scientific contributions retrieved from the PubMed database (supported with Google Scholar searching) over the last 5 years.
Topics: Humans; Wound Healing; Skin; Bandages; Anti-Bacterial Agents; Anti-Infective Agents; Wound Infection
PubMed: 37108356
DOI: 10.3390/ijms24087193 -
Drug Discovery Today Jun 2022Combination therapies can overcome antimicrobial resistance (AMR) and repurpose existing drugs. However, the large combinatorial space to explore presents a daunting... (Review)
Review
Combination therapies can overcome antimicrobial resistance (AMR) and repurpose existing drugs. However, the large combinatorial space to explore presents a daunting challenge. In response, machine learning (ML) algorithms are being applied to identify novel synergistic drug interactions from millions of potential combinations. Here, we compare ML-based approaches for combination therapy design based on the type of input information used, specifically: drug properties, microbial response and infection microenvironment. We also provide a compilation of publicly available drug interaction datasets relevant to AMR. Finally, we discuss limitations of current ML-based methods and propose new strategies for designing efficacious combination therapies. These include consideration of in vivo conditions, design of sequential combinations, enhancement of model interpretability and application of deep learning algorithms.
Topics: Algorithms; Anti-Bacterial Agents; Anti-Infective Agents; Machine Learning
PubMed: 35398560
DOI: 10.1016/j.drudis.2022.04.006 -
Current Opinion in Microbiology Feb 2023
Topics: Anti-Infective Agents; Drug Discovery
PubMed: 36423503
DOI: 10.1016/j.mib.2022.102242 -
Molecules (Basel, Switzerland) May 2023The emergence of the antimicrobial resistance phenomena on and the harmful consequences of the use of antibiotics motivate the necessity of innovative antimicrobial... (Review)
Review
The emergence of the antimicrobial resistance phenomena on and the harmful consequences of the use of antibiotics motivate the necessity of innovative antimicrobial therapies, while natural substances are considered a promising alternative. Rosmarin is an original plant compound listed among the hydroxycinnamic acids. This substance has been widely used to fight microbial pathology and chronic infections from microorganisms like bacteria, fungi and viruses. Also, various derivatives of rosmarinic acid, such as the propyl ester of rosmarinic acid, rosmarinic acid methyl ester or the hexyl ester of rosmarinic acid, have been synthesized chemically, which have been isolated as natural antimicrobial agents. Rosmarinic acid and its derivatives were combined with antibiotics to obtain a synergistic effect. This review reports on the antimicrobial effects of rosmarinic acid and its associated derivatives, both in their free form and in combination with other microbial pathogens, and mechanisms of action.
Topics: Anti-Infective Agents; Anti-Bacterial Agents; Esters; Rosmarinic Acid
PubMed: 37241981
DOI: 10.3390/molecules28104243 -
International Journal of Nanomedicine 2014Advances in nanotechnology are producing an accelerated proliferation of new nanomaterial composites that are likely to become an important source of engineered... (Review)
Review
Advances in nanotechnology are producing an accelerated proliferation of new nanomaterial composites that are likely to become an important source of engineered health-related products. Nanoparticles with antifungal effects are of great interest in the formulation of microbicidal materials. Fungi are found as innocuous commensals and colonize various habitats in and on humans, especially the skin and mucosa. As growth on surfaces is a natural part of the Candida spp. lifestyle, one can expect that Candida organisms colonize prosthetic devices, such as dentures. Macromolecular systems, due to their properties, allow efficient use of these materials in various fields, including the creation of reinforced nanoparticle polymers with antimicrobial activity. This review briefly summarizes the results of studies conducted during the past decade and especially in the last few years focused on the toxicity of different antimicrobial polymers and factors influencing their activities, as well as the main applications of antimicrobial polymers in dentistry. The present study addresses aspects that are often overlooked in nanotoxicology studies, such as careful time-dependent characterization of agglomeration and ion release.
Topics: Animals; Anti-Infective Agents; Biocompatible Materials; Cell Line; Dentures; Humans; Nanoparticles; Oxidative Stress; Prostheses and Implants; Rats; Toxicity Tests
PubMed: 25187703
DOI: 10.2147/IJN.S63064 -
Critical Reviews in Microbiology Feb 2021Biofilms are complex microbial architectures that encase microbial cells in a matrix comprising self-produced extracellular polymeric substances. Microorganisms living... (Review)
Review
Biofilms are complex microbial architectures that encase microbial cells in a matrix comprising self-produced extracellular polymeric substances. Microorganisms living in biofilms are much more resistant to hostile environments than their planktonic counterparts and exhibit enhanced resistance against the microbicides. From the human perspective, biofilms can be classified into beneficial, neutral, and harmful. Harmful biofilms impact food safety, cause plant and animal diseases, and threaten medical fields, making it urgent to develop effective and robust strategies to control harmful biofilms. In this review, we discuss various strategies to control biofilm formation on infected tissues, implants, and medical devices. We classify the current strategies into three main categories: (i) changing the properties of susceptible surfaces to prevent biofilm formation; (ii) regulating signalling pathways to inhibit biofilm formation; (iii) applying external forces to eradicate the biofilm. We hope this review would motivate the development of innovative and effective strategies for controlling harmful biofilms.
Topics: Animals; Anti-Infective Agents; Bacteria; Bacterial Infections; Bacterial Physiological Phenomena; Biofilms; Humans; Prostheses and Implants
PubMed: 33356690
DOI: 10.1080/1040841X.2020.1842325 -
World Journal of Microbiology &... Dec 2023The threat of fungal diseases is substantially underestimated worldwide, but they have serious consequences for humans, animals, and plants. Given the limited number of... (Review)
Review
The threat of fungal diseases is substantially underestimated worldwide, but they have serious consequences for humans, animals, and plants. Given the limited number of existing antifungal drugs together with the emergence of drug-resistant strains, many researchers have actively sought alternatives or adjuvants to antimycotics. The best way to tackle these issues is to unearth potential antifungal agents with new modes of action. Antimicrobial peptides are being hailed as a promising source of novel antimicrobials since they exhibit rapid and broad-spectrum microbicidal activities with a reduced likelihood of developing drug resistance. Recent years have witnessed an explosion in knowledge on microbicidal activity of LL-37, the sole human cathelicidin. Herein, we provide a summary of the current understanding about antifungal properties of LL-37, with particular emphasis on its molecular mechanisms. We further illustrate fruitful areas for future research. LL-37 is able to inhibit the growth of clinically and agronomically relevant fungi including Aspergillus, Candida, Colletotrichum, Fusarium, Malassezia, Pythium, and Trichophyton. Destruction of the cell wall integrity, membrane permeabilization, induction of oxidative stress, disruption of endoplasmic reticulum homeostasis, formation of autophagy-like structures, alterations in expression of numerous fungal genes, and inhibition of cell cycle progression are the key mechanisms underlying antifungal effects of LL-37. Burgeoning evidence also suggests that LL-37 may act as a potential anti-virulence peptide. It is hoped that this review will not only motivate researchers to conduct more detailed studies in this field, but also inspire further innovations in the design of LL-37-based drugs for the treatment of fungal infections.
Topics: Animals; Humans; Cathelicidins; Antifungal Agents; Antimicrobial Cationic Peptides; Anti-Infective Agents; Candida
PubMed: 38057654
DOI: 10.1007/s11274-023-03852-5 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Female; Anti-Bacterial Agents; Drug Resistance, Bacterial; Anti-Infective Agents
PubMed: 37692172
DOI: 10.3389/fcimb.2023.1263568 -
Molecules (Basel, Switzerland) Jan 2023The use of essential oils is increasingly being investigated among new therapeutic approaches based on medicinal plants and their extracts. With the wide use of... (Review)
Review
The use of essential oils is increasingly being investigated among new therapeutic approaches based on medicinal plants and their extracts. With the wide use of synthetic and semi-synthetic antimicrobial drugs, the spread of drug-resistant clinical isolates has increased, and research is directed towards natural products, such as essential oils, as useful antimicrobial resources. In the context of a prospective infection, we compared the impact of essential oils and common antimicrobial agents on the microbicidal activity of human phagocytes. Here, we present the results of our decades-long investigation into the effectiveness of thyme red oil (26.52% thymol chemotype), tea tree oil (TTO), and Mentha of Pancalieri [( (Huds) var. (Sole), form (Camus) ()] essential oils on human polymorphonuclear leukocytes (PMNs) capacity to kill clinical strains of and when compared to three antifungal drugs used to treat candidiasis (fluconazole, anidulafungin, and caspofungin) These essential oils demonstrate antifungal drug-like and/or superior efficacy in enhancing intracellular killing by PMNs, even at subinhibitory concentrations. Our results are compared with data in the literature on essential oils and immune system interactions. This comparison would aid in identifying therapeutic solutions to the increasingly prevalent antibiotic resistance as well as filling in any remaining knowledge gaps on the bioactivity of essential oils.
Topics: Humans; Oils, Volatile; Antifungal Agents; Prospective Studies; Fluconazole; Plant Oils; Anti-Infective Agents; Microbial Sensitivity Tests
PubMed: 36615625
DOI: 10.3390/molecules28010435