Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for Sustainable Medicine?

2018 ◽  
Vol 25 (21) ◽  
pp. 2503-2519 ◽  
Author(s):  
Anne Kokel ◽  
Marianna Torok
Keyword(s):  
Side Effects ◽  
Antimicrobial Peptides ◽  
Potential Drug ◽  
Green Technologies ◽  
Specific Antibodies ◽  
Structural Modifications ◽  
Drug Candidates ◽  
Induce Resistance ◽  
Conventional Antibiotics

Background: Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. Methods: In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. Results: As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Conclusion: Although further research is needed taking into account both environmental and human health consequences of novel AMPs, several of these compounds are promising drug candidates for use in sustainable medicine.

scholarly journals Medicinal Utility of Some Schiff Bases and their Complexes with First Transition Series Metals: A Review

2021 ◽  
Vol 37 (5) ◽  
pp. 1051-1061
Author(s):  
Tahmeena Khan ◽  
Saima Zehra ◽  
Almas Alvi ◽  
Umama Fatima ◽  
Alfred J. Lawrence
Keyword(s):  
Transition Metal ◽  
Metal Complexes ◽  
Transition Metal Complexes ◽  
Present Review ◽  
Potential Drug ◽  
Drug Candidates ◽  
Transition Series ◽  
Low Toxicity ◽  
Activity Enhancement

Schiff based ligands and their complexes have emerged as potential drug candidates. Owing to their excellent chelating tendency, they easily coordinate with transition metals which have vacant orbitals. Transition metal complexes have several advantages because of their better acceptability and low toxicity in biological systems. These metals also serve as micronutrients and as co-factors of various metallo-enzymes which justifies the need of their designing and synthesis. Many modifications have been suggested in the ligand moiety for the purpose of activity enhancement and some of them have been described in the present review. These modifications have enhanced better potency against a number of diseases and resulting in low toxicity and better solubility in vivo. The transition metal complexes with Schiff based complexes have exhibited an array of activities including anticancer, antioxidant and antimicrobial. Their analytical applications have also been reported. The present review summarizes some of the recent advances in the field of synthesis and designing of new Schiff based complexes particularly with first transition series metals and their medicinal applications.

Abstract 3306: Screening potential drug candidates for treatment of glioblastoma patients utilizing an in-vivo mouse/ rat model system

2011 ◽  
Author(s):  
Jenna Passarini ◽  
John P. Cleary ◽  
Preetham Kumar ◽  
Trisha Newton ◽  
Michael Sharma ◽  
...  
Keyword(s):  
Rat Model ◽  
Model System ◽  
Potential Drug ◽  
Drug Candidates

Antimicrobial peptides: an overview of a promising class of therapeutics

2007 ◽  
Vol 2 (1) ◽  
pp. 1-33 ◽  
Author(s):  
Andrea Giuliani ◽  
Giovanna Pirri ◽  
Silvia Nicoletto
Keyword(s):  
Antimicrobial Peptides ◽  
Multidrug Resistant ◽  
Innate Immune ◽  
Resistant Bacteria ◽  
Yeast Fungi ◽  
Wide Range ◽  
New Development ◽  
Catheter Site ◽  
Conventional Antibiotics

AbstractAntibiotic resistance is increasing at a rate that far exceeds the pace of new development of drugs. Antimicrobial peptides, both synthetic and from natural sources, have raised interest as pathogens become resistant against conventional antibiotics. Indeed, one of the major strengths of this class of molecules is their ability to kill multidrug-resistant bacteria. Antimicrobial peptides are relatively small (6 to 100 aminoacids), amphipathic molecules of variable length, sequence and structure with activity against a wide range of microorganisms including bacteria, protozoa, yeast, fungi, viruses and even tumor cells. They usually act through relatively non-specific mechanisms resulting in membranolytic activity but they can also stimulate the innate immune response. Several peptides have already entered pre-clinical and clinical trials for the treatment of catheter site infections, cystic fibrosis, acne, wound healing and patients undergoing stem cell transplantation. We review the advantages of these molecules in clinical applications, their disadvantages including their low in vivo stability, high costs of production and the strategies for their discovery and optimization.

scholarly journals Antimicrobial peptides and bacteriocins: alternatives to traditional antibiotics

2008 ◽  
Vol 9 (2) ◽  
pp. 227-235 ◽  
Author(s):  
Yongming Sang ◽  
Frank Blecha
Keyword(s):  
Antimicrobial Peptides ◽  
Membrane Integrity ◽  
Principal Component ◽  
Protective Response ◽  
Antimicrobial Drugs ◽  
Induce Resistance ◽  
Unicellular Organisms ◽  
Conventional Antibiotics ◽  
Multicellular Organisms ◽  
Recent Attention

AbstractAntimicrobial peptides (AMPs) are ubiquitous, gene-encoded natural antibiotics that have gained recent attention in the search for new antimicrobials to combat infectious disease. In multicellular organisms, AMPs, such as defensins and cathelicidins, provide a coordinated protective response against infection and are a principal component of innate immunity in vertebrates. In unicellular organisms, AMPs, such as bacteriocins, function to suppress competitor species. Because many AMPs kill bacteria by disruption of membrane integrity and are thus thought to be less likely to induce resistance, AMPs are being extensively evaluated as novel antimicrobial drugs. This review summarizes and discusses the antibiotic properties of AMPs highlighting their potential as alternatives to conventional antibiotics.

scholarly journals Computational screening for potential drug candidates against the SARS-CoV-2 main protease

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 514 ◽  
Author(s):  
Bruno Silva Andrade ◽  
Preetam Ghosh ◽  
Debmalya Barh ◽  
Sandeep Tiwari ◽  
Raner José Santana Silva ◽  
...  
Keyword(s):  
Natural Compounds ◽  
Potential Drug ◽  
Drug Candidates ◽  
Positive Effects ◽  
Computational Screening ◽  
Main Protease ◽  
Zinc Database ◽  
Structural Assembly

Background: SARS-CoV-2 is the causal agent of the current coronavirus disease 2019 (COVID-19) pandemic. They are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity. The approximately 33.8 kDa Mpro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that Mpro could be a potential drug target for Coronaviruses. Methods: Herein, we performed computational ligand screening of four pharmacophores (OEW, remdesivir, hydroxychloroquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7), and also screened 50,000 natural compounds from the ZINC Database dataset against this protease target. Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 11 best selected ligands, namely ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as beta-carboline, alkaloids, and polyflavonoids, and all displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as other known ligands. Conclusions: Our results suggest that these 11 molecules could be effective against SARS-CoV-2 protease and may be subsequently tested in vitro and in vivo to develop novel drugs against this virus.

scholarly journals A Uniform In Vitro Efficacy Dataset to Guide Antimicrobial Peptide Design

Data ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 27 ◽  
Author(s):  
Deepesh Nagarajan ◽  
Tushar Nagarajan ◽  
Neha Nanajkar ◽  
Nagasuma Chandra
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Antimicrobial Agents ◽  
Multi Drug Resistance ◽  
Peptide Design ◽  
Drug Candidates ◽  
The Face ◽  
Conventional Antibiotics ◽  
Different Sources

Antimicrobial peptides are ubiquitous molecules that form the innate immune system of organisms across all kingdoms of life. Despite their prevalence and early origins, they continue to remain potent natural antimicrobial agents. Antimicrobial peptides are therefore promising drug candidates in the face of overwhelming multi-drug resistance to conventional antibiotics. Over the past few decades, thousands of antimicrobial peptides have been characterized in vitro, and their efficacy data are now available in a multitude of public databases. Computational antimicrobial peptide design attempts typically use such data. However, utilizing heterogenous data aggregated from different sources presents significant drawbacks. In this report, we present a uniform dataset containing 20 antimicrobial peptides assayed against 30 organisms of Gram-negative, Gram-positive, mycobacterial, and fungal origin. We also present circular dichroism spectra for all antimicrobial peptides. We draw simple inferences from this data, and we discuss what characteristics are essential for antimicrobial peptide efficacy. We expect our uniform dataset to be useful for future projects involving computational antimicrobial peptide design.

scholarly journals Lipidation of Temporin-1CEb Derivatives as a Tool for Activity Improvement, Pros and Cons of the Approach

2021 ◽  
Vol 22 (13) ◽  
pp. 6679
Author(s):  
Paulina Kosikowska-Adamus ◽  
Emilia Sikorska ◽  
Dariusz Wyrzykowski ◽  
Aleksandra Walewska ◽  
Anna Golda ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptides ◽  
Antimicrobial Properties ◽  
Carbon Chain ◽  
Microbial Pathogens ◽  
Multi Drug Resistance ◽  
Aggregation State ◽  
Conventional Antibiotics ◽  
Biofilm Development

The alarming raise of multi-drug resistance among human microbial pathogens makes the development of novel therapeutics a priority task. In contrast to conventional antibiotics, antimicrobial peptides (AMPs), besides evoking a broad spectrum of activity against microorganisms, could offer additional benefits, such as the ability to neutralize toxins, modulate inflammatory response, eradicate bacterial and fungal biofilms or prevent their development. The latter properties are of special interest, as most antibiotics available on the market have limited ability to diffuse through rigid structures of biofilms. Lipidation of AMPs is considered as an effective approach for enhancement of their antimicrobial potential and in vivo stability; however, it could also have undesired impact on selectivity, solubility or the aggregation state of the modified peptides. In the present work, we describe the results of structural modifications of compounds designed based on cationic antimicrobial peptides DK5 and CAR-PEG-DK5, derivatized at their N-terminal part with fatty acids with different lengths of carbon chain. The proposed modifications substantially improved antimicrobial properties of the final compounds and their effectiveness in inhibition of biofilm development as well as eradication of pre-formed 24 h old biofilms of Candida albicans and Staphylococcus aureus. The most active compounds (C5-DK5, C12-DK5 and C12-CAR-PEG-DK5) were also potent against multi-drug resistant Staphylococcus aureus USA300 strain and clinical isolates of Pseudomonas aeruginosa. Both experimental and in silico methods revealed strong correlation between the length of fatty acid attached to the peptides and their final membranolytic properties, tendency to self-assemble and cytotoxicity.

scholarly journals Computer-Aided Prediction and Identification of Phytochemicals as Potential Drug Candidates against MERS-CoV

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Hafiza Salaha Mahrosh ◽  
Muhammad Tanveer ◽  
Rawaba Arif ◽  
Ghulam Mustafa
Keyword(s):  
Respiratory Infections ◽  
Catalytic Triad ◽  
World Health ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Potential Drug ◽  
Drug Candidates ◽  
Starting Point ◽  
Computer Aided

The Middle East respiratory syndrome coronavirus (MERS-CoV) is the major leading cause of respiratory infections listed as blueprint of diseases by the World Health Organization. It needs immediate research in the developing countries including Saudi Arabia, South Korea, and China. Still no vaccine has been developed against MERS-CoV; therefore, an effective strategy is required to overcome the devastating outcomes of MERS. Computer-aided drug design is the effective method to find out potency of natural phytochemicals as inhibitors of MERS-CoV. In the current study, the molecular docking approach was employed to target receptor binding of CoV. A total of 150 phytochemicals were docked as ligands in this study and found that some of the phytochemicals successfully inhibited the catalytic triad of MERS-CoV. The docking results brought novel scaffolds which showed strong ligand interactions with Arg178, Arg339, His311, His230, Lys146, and Arg139 residues of the viral domains. From the top ten ligands found in this study (i.e., rosavin, betaxanthin, quercetin, citromitin, pluviatilol, digitogenin, ichangin, methyl deacetylnomilinate, kobusinol A, and cyclocalamin) based on best S -score values, two phytochemicals (i.e., pluviatilol and kobusinol A) exhibited all drug-likeness properties following the pharmacokinetic parameters which are important for bioavailability of drug-like compounds, and hence, they can serve as potential drug candidates to stop the viral load. The study revealed that these phytochemicals would serve as strong potential inhibitors and a starting point for the development of vaccines and proteases against MERS-CoV. Further, in vivo studies are needed to confirm the efficacy of these potential drug candidates.

Sign in / Sign up

Export Citation Format

Share Document