Nature’s Toolbox for the Hydrolysis of Lactams and Cyclic Imides DOI Creative Commons
Peter Stockinger, Rebecca Buller

ACS Catalysis, Год журнала: 2024, Номер 14(21), С. 16055 - 16073

Опубликована: Окт. 16, 2024

Hydrolytic enzymes, such as lactamases or hydantoinases, can be valuably applied to convert lactams (cyclic amides) and cyclic imides into optically pure compounds, for example, d- l- amino acids, resolve racemic mixtures, Vince lactams. The chiral building blocks utilized produce biologically active peptides, pesticides, sweeteners, antibiotics, semisynthetic penicillins cephalosporins. Furthermore, these compounds find application feed food additives constitute useful intermediates cosmetics, pharmaceuticals, agrochemicals. Beyond their in chemical synthesis, amide imide hydrolyzing enzymes hold promise the recovery of materials containing polyamides bioremediation antibiotics herbicides. Today, lactam biocatalysts mainly originate from enzyme families associated with two distinct structural archetypes: (a) α/β-hydrolases (e.g., lipases) (b) metal-dependent amidohydrolases dihydropyrimidinases/hydantoinases). well-explored sources, nature offers an additional wealth mechanistically, catalytically, structurally hydrolysis, including serine metallo-β-lactamases, allantoinases, 5-oxoprolinases, members amidase signature family. To facilitate discovery suitable types hydrolysis reactions, we provide a comprehensive overview examples, well functional annotations (EC identifiers) architectures (CATH identifiers), currently known biocatalytic toolbox. In addition, protein sequence database all relevant biocatalyst superfamilies has been created (https://github.com/ccbiozhaw/CyclAmidImid).

Язык: Английский

Microbiome-Driven Therapeutics: From Gut Health to Precision Medicine DOI Creative Commons
Muneer Yaqub,

Aashika Jain,

Chinedu Eucharia Joseph

и другие.

Gastrointestinal Disorders, Год журнала: 2025, Номер 7(1), С. 7 - 7

Опубликована: Янв. 15, 2025

The human microbiome, a complex ecosystem of microorganisms residing in and on the body, plays pivotal role regulation wide range physiological processes, including digestion, immune responses, metabolic functions. In recent years, rapidly growing field microbiome-driven therapeutics has garnered significant attention owing to its potential revolutionize healthcare. This review explores evolving landscape microbiome-based therapies, with particular focus gut microbiome implications for both health precision medicine. We highlight advances understanding how microbial communities influence disease pathogenesis treatment outcomes, spanning conditions such as inflammatory bowel (IBD), disorders, neurological diseases, even cancer. article also discusses emerging therapeutic strategies, probiotics, prebiotics, fecal microbiota transplantation (FMT), microbial-based drugs, well challenges associated their clinical implementation. Additionally, we examined integration profiling metagenomic data is advancing medicine, paving way personalized effective treatments. serves comprehensive resource that synthesizes current knowledge, identifies key gaps research, offers insights into future direction therapeutics, thus providing valuable framework clinicians, researchers, policymakers seeking harness microbiomes advance healthcare solutions.

Язык: Английский

Процитировано

2
Synthesis, Biological Properties, In Silico ADME, Molecular Docking Studies, and FMO Analysis of Chalcone Derivatives as Promising Antioxidant and Antimicrobial Agents DOI Creative Commons
Md. R. U. Ahsan, Sony Paul, Mohammad Sayed Alam

и другие.

ACS Omega, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

A series of chalcone derivatives were synthesized and characterized using UV–vis, FT-IR, 1H NMR, mass spectrometry, followed by the evaluation their antimicrobial antioxidant properties. In vitro screening against six bacterial strains (Staphylococcus aureus, Bacillus subtilis, Salmonella typhimurium, Escherichia coli, Pseudomonas aeruginosa, Citrobacter freundii) two fungal (Aspergillus niger Trichoderma harzianum) revealed outstanding antibacterial activities, particularly with compound 5b, 5d, 5e S. compounds 5c 5h B. subtilis. Notably, 5f 5g exhibited significant effects P. while 5b showed highest antifungal activity T. harzianum. All demonstrated remarkable (IC50 values 0.005 μM) 0.006 being most potent, comparable to ascorbic acid 0.007 μM). silico evaluations confirmed favorable drug-likeness pharmacokinetic properties for all analogues, adhering both Lipinski's rule Five Veber's rule. Molecular docking studies potent (5e 5h) indicated strong binding affinities PBP-1b receptor in DFT calculations provided valuable insights into molecular reactivity biological Ligand-based enzymatic target predictions indicate that analogues (5a–m) show potential as inhibitors oxidoreductases, kinases, enzymes, proteases, or ligands family GPCR. These findings position promising candidates therapeutic applications combating infections oxidative stress.

Язык: Английский

Процитировано

1
Virtual Screening of Potential Inhibitors against the Penicillin-Binding Protein 1a (PBP1a) of Streptococcus pneumoniae DOI

Adnan Shehzad,

Farkhanda,

Shah Zainab

и другие.

Indus journal of bioscience research., Год журнала: 2025, Номер 3(3), С. 181 - 185

Опубликована: Март 18, 2025

Background: Pneumonia is an inflammatory condition of the lungs caused by bacterium Streptococcus pneumoniae. It a significant cause mortality and morbidity, particularly among young children, adults immunocompromised persons. Resistance against drugs continuously evolving in nearly all pathogens. The constant need for alternative therapeutic options demands necessity ongoing search novel drugs. current study was thus designed to target penicillin binding protein pneumoniae (PBP1a), involved critical cellular metabolic processes.Method: PBP1a sequence obtained from UniProt database BLAST performed. 3D structure downloaded RCSB visualized using Discovery Studio Visualizer. 150 were docked PatchDock web server interactions explored GS Viewer, LigPlot+ Visualizer.Result: Out chosen, Lamivudine, Dolutegravir Loperamide showed most with PBP1a. These included covalent bonds, hydrogen bonds hydrophobic interactions. Conclusion: interacted uniquely protein. may trigger changes could inhibit growth kill parasite. Further experimental needed fully understand potential these

Язык: Английский

Процитировано

0
A Review of In Silico and In Vitro Approaches in the Fight Against Carbapenem‐Resistant Enterobacterales DOI Creative Commons

Muhammad Absar,

Abdul Rahman Zaidah, Amer Mahmood

и другие.

Journal of Clinical Laboratory Analysis, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

ABSTRACT Objectives The rise in carbapenem‐resistant Enterobacterales (CRE) has reinforced the global quest for developing effective therapeutics. Traditional drug discovery approaches have been inadequate overcoming this challenge due to their resource and time constraints. Methods English literature was searched by structured queries related our review between January 1, 2020, December 31, 2024. Results key resistance mechanisms CRE, such as enzymatic hydrolysis, decreased permeability, efflux pump overexpression, examined review. Computational technologies become pivotal discovering novel antimicrobial agents with improved accuracy efficiency. Besides this, highlights advances structure‐ ligand‐based identifying potential drugs against CRE. Recent studies demonstrating use of silico techniques develop targeted CRE also explored. Moreover, underscores significance integrating both vitro counter Enterobacterales, supported latest studies. However, these promising computational a few major drawbacks, lack standardized parameterization, potentially false positives, complexity clinical translations. regulatory barriers restrict progress new antimicrobials market approval. Conclusion inhibitor is gaining popularity, it can be expedited refining them reliable validation. innovative hybrid need hour tackle mitigate threat resistance.

Язык: Английский

Процитировано

0
Recent progress in synthetic strategies for novel β-lactams linked with five-membered heterocycles (N/O/S): advances in medicinal chemistry (2020–2025) DOI

Ankita Garg,

Dolar Dureja,

Raaina Pasricha

и другие.

Medicinal Chemistry Research, Год журнала: 2025, Номер unknown

Опубликована: Апрель 12, 2025

Язык: Английский

Процитировано

0
Medicinal plants: bioactive compounds, biological activities, combating multidrug-resistant microorganisms, and human health benefits - a comprehensive review DOI Creative Commons
Mohamed T. El‐Saadony, Ahmed M. Saad, Dina Mostafa Mohammed

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 28, 2025

In recent years, medicinal plants have gained significant attention in modern medicine due to their accessibility, affordability, widespread acceptance, and safety, making herbal remedies highly valued globally. Consequently, ensuring plants’ quality, efficacy, safety has become a critical concern for developed developing nations. The emergence of multidrug-resistant microorganisms poses serious global health threat, particularly low-income regions, despite advancements antimicrobial drugs medical research over the past century. rapid spread these infections is primarily attributed improper prescriptions, overuse, unregulated access antibiotics. Addressing challenges, standardization plant-derived pharmaceuticals could pave way transformative era healthcare. Preserving leveraging historical knowledge essential before such valuable information lost. Recently, there been growing interest among natural pharmaceutical scientists exploring as potential sources agents. This current review aims identify most common pathogens threatening human health, analyze factors contributing rise drug-resistant microorganisms, evaluate use across various countries alternative antibiotics, highlighting unique mechanisms resistance.

Язык: Английский

Процитировано

0
Production of Natural Penicillin-Binding Protein 2 and Development of a Signal-Amplified Fluorescence Polarization Assay for the Determination of 28 Beta-Lactam Antibiotics in Milk DOI

Jia Hu,

Jian Ping Wang

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 25, 2024

In this study, two magnetic activity-based protein profiling probes based on cephradine and amoxicillin were first synthesized that used to produce the natural penicillin-binding 2 of

Язык: Английский

Процитировано

1
Cannabidiol Interactions with Outer Membrane Proteins in Salmonella Typhimurium LT2 DOI Creative Commons
Iddrisu Ibrahim, Emmanuel Ndezure,

Junhuan Xu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 7, 2024

Abstract Cannabidiol (CBD), the non-psychoactive component of hemp plant has tremendous potential as a novel antimicrobial agent. This study aimed at understanding interactions between CBD and outer membrane proteins (OMPs) Salmonella Typhimurium LT2. Employing in silico techniques, we analyzed binding affinities, interaction dynamics, drug-likeness with key OMPs such OmpA, OmpC, OmpD, OmpF, OmpX, NompC. The molecular docking results showed that exhibits varying affinities across OMPs, OmpX NompC showing highest affinity -6.6 kcal/mol − 6.4 respectively, indicating strong stable interactions. also revealed several hydrogen bonds, Pi-stacking, hydrophobic interactions, playing crucial roles in stability specificity these protein-ligand complexes. Notable were identified OmpA -5.9 involving bonds 3.2 Å Pi-Sigma 3.4 Å. We included phylogenetic analysis fifty different strains Typhimurium, observed high conservation levels among sequence similarity threshold 90%. underscores to act broad-spectrum Furthermore, our comparative structural both conserved variable regions within highlighting significance targeting mitigate resistance development. Using KEGG Pathway analysis, OmpC given their nutrient transport permeability. disruption pathways by could impair bacteria’s ability manage environmental stresses evade host immune responses. Beta-lactam pathway was considered, potentially disrupt mechanisms enhancing efficacy existing treatments. In conclusion, findings suggest CBD, through its critical serve potent agent against These lay foundation for further studies therapeutic combating bacterial infections addressing global challenge antibiotic resistance.

Язык: Английский

Процитировано

0
Nature’s Toolbox for the Hydrolysis of Lactams and Cyclic Imides DOI Creative Commons
Peter Stockinger, Rebecca Buller

ACS Catalysis, Год журнала: 2024, Номер 14(21), С. 16055 - 16073

Опубликована: Окт. 16, 2024

Hydrolytic enzymes, such as lactamases or hydantoinases, can be valuably applied to convert lactams (cyclic amides) and cyclic imides into optically pure compounds, for example, d- l- amino acids, resolve racemic mixtures, Vince lactams. The chiral building blocks utilized produce biologically active peptides, pesticides, sweeteners, antibiotics, semisynthetic penicillins cephalosporins. Furthermore, these compounds find application feed food additives constitute useful intermediates cosmetics, pharmaceuticals, agrochemicals. Beyond their in chemical synthesis, amide imide hydrolyzing enzymes hold promise the recovery of materials containing polyamides bioremediation antibiotics herbicides. Today, lactam biocatalysts mainly originate from enzyme families associated with two distinct structural archetypes: (a) α/β-hydrolases (e.g., lipases) (b) metal-dependent amidohydrolases dihydropyrimidinases/hydantoinases). well-explored sources, nature offers an additional wealth mechanistically, catalytically, structurally hydrolysis, including serine metallo-β-lactamases, allantoinases, 5-oxoprolinases, members amidase signature family. To facilitate discovery suitable types hydrolysis reactions, we provide a comprehensive overview examples, well functional annotations (EC identifiers) architectures (CATH identifiers), currently known biocatalytic toolbox. In addition, protein sequence database all relevant biocatalyst superfamilies has been created (https://github.com/ccbiozhaw/CyclAmidImid).

Язык: Английский

Процитировано

0