Special Issue "Enzymatic Inhibitors from Natural Sources: A Huge Collection of New Potential Drugs 2022"

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Enzymology".

Deadline for manuscript submissions: closed (20 November 2022) | Viewed by 2203

Special Issue Editors

Dipartimento di Scienze Biomediche, Sperimentali e Cliniche Mario Serio Università degli Studi di Firenze, Florence, Italy
Interests: drug discovery; type 2 diabetes; insulin resistance; protein tyrosine phosphatase; cancer cell metabolism; chemoresistance; targeted therapy
Special Issues, Collections and Topics in MDPI journals
Dipartimento di Scienze Biomediche, Sperimentali e Cliniche Mario Serio Università degli Studi di Firenze, Florence, Italy
Interests: n vitro and ex vivo, of anti-diabetical properties of natural compounds and the evaluation of novel drugs; eco-toxicological impact of novel pollutants

Special Issue Information

Dear Colleagues,

The natural world is undoubtedly the largest collection of molecules with medical properties known by humankind. This is confirmed by the fact that every year, hundreds of new natural inhibitors are derived from the natural world and able to target important biological human proteins or enzymes are identified and characterized. In the last decades, some of these molecules have been considered promising therapeutic molecules because of their high selectivity or potency and have been included in clinical trials to evaluate their effectiveness.

This Special Issue aims to highlight the properties of natural inhibitors and the advantages that could be obtained from their use as drugs for the treatment of human diseases, including cancer, neurodegenerative diseases, diabetes, chronic inflammation, bacterial infections  and obesity. We encourage all researchers interested in this topic to present research articles or reviews concerning natural compounds that act as inhibitors of specific biological targets. This Special Issue can include structure–activity relationship studies, analyses of the mechanisms of action of these inhibitors, crystallographic analyses of target–inhibitor complexes and studies about specificity, bioavailability, toxicity and effectiveness of new inhibitors both in vitro and in vivo, as well as results of clinical trials carried out to evaluate the effectiveness of natural inhibitors in humans.

Prof. Paolo Paoli
Dr. Massimo Genovese
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 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 molecules
  • Inhibitors
  • Drugs
  • Inhibition mechanism
  • Toxicity
  • Bioavailability
  • Target therapy
  • Crystallography
  • Ligand affinity
  • Docking in silico
  • Targeted therapy

Published Papers (1 paper)

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Research

16 pages, 3146 KiB  
Article
Glycosylated Flavonoid Compounds as Potent CYP121 Inhibitors of Mycobacterium tuberculosis
Biomolecules 2022, 12(10), 1356; https://doi.org/10.3390/biom12101356 - 23 Sep 2022
Cited by 6 | Viewed by 1517
Abstract
Due to the concerning rise in the number of multiple- and prolonged-drug-resistant (MDR and XDR) Mycobacterium tuberculosis (Mtb) strains, unprecedented demand has been created to design and develop novel therapeutic drugs with higher efficacy and safety. In this study, with a focused view [...] Read more.
Due to the concerning rise in the number of multiple- and prolonged-drug-resistant (MDR and XDR) Mycobacterium tuberculosis (Mtb) strains, unprecedented demand has been created to design and develop novel therapeutic drugs with higher efficacy and safety. In this study, with a focused view on implementing an in silico drug design pipeline, a diverse set of glycosylated flavonoids were screened against the Mtb cytochrome-P450 enzyme 121 (CYP121), which is established as an approved drug target for the treatment of Mtb infection. A total of 148 glycosylated flavonoids were screened using structure-based virtual screening against the crystallized ligand, i.e., the L44 inhibitor, binding pocket in the Mtb CYP121 protein. Following this, only the top six compounds with the highest binding scores (kcal/mol) were considered for further intermolecular interaction and dynamic stability using 100 ns classical molecular dynamics simulation. These results suggested a considerable number of hydrogen and hydrophobic interactions and thermodynamic stability in comparison to the reference complex, i.e., the CYP121-L44 inhibitor. Furthermore, binding free energy via the MMGBSA method conducted on the last 10 ns interval of MD simulation trajectories revealed the substantial affinity of glycosylated compounds with Mtb CYP121 protein against reference complex. Notably, both the docked poses and residual energy decomposition via the MMGBSA method demonstrated the essential role of active residues in the interactions with glycosylated compounds by comparison with the reference complex. Collectively, this study demonstrates the viability of these screened glycosylated flavonoids as potential inhibitors of Mtb CYP121 for further experimental validation to develop a therapy for the treatment of drug-resistant Mtb strains. Full article
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