Marine Drug Discovery through Molecular Docking

A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Marine Pharmacology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 4519

Special Issue Editors


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Guest Editor
Bioorganic Chemistry Laboratory, Department of Physics, University of Trento, Via Sommarive 14, I-38123 Povo-Trento, Italy
Interests: marine natural products; structural characterization; medicinal chemistry; structure–activity relationship (SAR) studies; organic synthesis; virtual screening
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Guest Editor
External Collaborator of Bioorganic Chemistry Laboratory, Department of Physics, University of Trento, Via Sommarive 14, I-38123 Povo-Trento, Italy
Interests: molecular docking; molecular dynamics; density functional theory (DFT) calculation; in silico screening; drug design; organic synthesis.

Special Issue Information

Dear Colleagues,                

Marine natural products have increasingly become major players in recent drug discovery. Due to their peculiar structures, they are able to enrich the chemical space of biologically active molecules. The study of them in medicinal chemistry is carried out using an iterative transdisciplinary approach, employing innovative technologies which benefit from spectroscopic, synthetic and computational tools. In the rational design of a potential drug inspired by a natural hit scaffold, the optimization takes advantage of in silico screening where docking with macromolecular targets is able to select the best candidates, later synthesised for biological investigation. Through structure–activity relationship (SAR) studies, the most promising candidates are identified, showing the best physico-chemical and pharmacological properties, which are predicted using a computational approach.

The purpose of this Special Issue is to collect papers on these topics. We strongly encourage the submission of articles showcasing your current research as well as critical overviews of the existing literature.

Prof. Ines Mancini
Dr. Andrea Defant
Guest Editors

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. Marine Drugs 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

  • molecular docking
  • marine metabolites
  • medicinal chemistry
  • in silico screening
  • drug-target interaction
  • drug design
  • structure-activity relationship (SAR)
  • lead optimization

Published Papers (3 papers)

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Research

15 pages, 1736 KiB  
Article
Structural Insights into the Marine Alkaloid Discorhabdin G as a Scaffold towards New Acetylcholinesterase Inhibitors
by Andrea Defant, Giacomo Carloni, Nicole Innocenti, Tomaž Trobec, Robert Frangež, Kristina Sepčić and Ines Mancini
Mar. Drugs 2024, 22(4), 173; https://doi.org/10.3390/md22040173 - 12 Apr 2024
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Abstract
In this study, Antarctic Latrunculia sponge-derived discorhabdin G was considered a hit for developing potential lead compounds acting as cholinesterase inhibitors. The hypothesis on the pharmacophore moiety suggested through molecular docking allowed us to simplify the structure of the metabolite. ADME prediction and [...] Read more.
In this study, Antarctic Latrunculia sponge-derived discorhabdin G was considered a hit for developing potential lead compounds acting as cholinesterase inhibitors. The hypothesis on the pharmacophore moiety suggested through molecular docking allowed us to simplify the structure of the metabolite. ADME prediction and drug-likeness consideration provided valuable support in selecting 5-methyl-2H-benzo[h]imidazo[1,5,4-de]quinoxalin-7(3H)-one as a candidate molecule. It was synthesized in a four-step sequence starting from 2,3-dichloronaphthalene-1,4-dione and evaluated as an inhibitor of electric eel acetylcholinesterase (eeAChE), human recombinant AChE (hAChE), and horse serum butyrylcholinesterase (BChE), together with other analogs obtained by the same synthesis. The candidate molecule showed a slightly lower inhibitory potential against eeAChE but better inhibitory activity against hAChE than discorhabdin G, with a higher selectivity for AChEs than for BChE. It acted as a reversible competitive inhibitor, as previously observed for the natural alkaloid. The findings from the in vitro assay were relatively consistent with the data available from the AutoDock Vina and Protein-Ligand ANTSystem (PLANTS) calculations. Full article
(This article belongs to the Special Issue Marine Drug Discovery through Molecular Docking)
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19 pages, 9574 KiB  
Article
Identification of PLK1-PBD Inhibitors from the Library of Marine Natural Products: 3D QSAR Pharmacophore, ADMET, Scaffold Hopping, Molecular Docking, and Molecular Dynamics Study
by Nan Zhou, Chuangze Zheng, Huiting Tan and Lianxiang Luo
Mar. Drugs 2024, 22(2), 83; https://doi.org/10.3390/md22020083 - 10 Feb 2024
Viewed by 1574
Abstract
PLK1 is found to be highly expressed in various types of cancers, but the development of inhibitors for it has been slow. Most inhibitors are still in clinical stages, and many lack the necessary selectivity and anti-tumor effects. This study aimed to create [...] Read more.
PLK1 is found to be highly expressed in various types of cancers, but the development of inhibitors for it has been slow. Most inhibitors are still in clinical stages, and many lack the necessary selectivity and anti-tumor effects. This study aimed to create new inhibitors for the PLK1-PBD by focusing on the PBD binding domain, which has the potential for greater selectivity. A 3D QSAR model was developed using a dataset of 112 compounds to evaluate 500 molecules. ADMET prediction was then used to select three molecules with strong drug-like characteristics. Scaffold hopping was employed to reconstruct 98 new compounds with improved drug-like properties and increased activity. Molecular docking was used to compare the efficient compound abbapolin, confirming the high-activity status of [(14S)-14-hydroxy-14-(pyridin-2-yl)tetradecyl]ammonium,[(14S)-15-(2-furyl)-14-hydroxypentadecyl]ammonium and [(14S)-14-hydroxy-14-phenyltetradecyl]ammonium. Molecular dynamics simulations and MMPBSA were conducted to evaluate the stability of the compounds in the presence of proteins. An in-depth analysis of [(14S)-15-(2-furyl)-14-hydroxypentadecyl]ammonium and [(14S)-14-hydroxy-14-phenyltetradecyl]ammonium identified them as potential candidates for PLK1 inhibitors. Full article
(This article belongs to the Special Issue Marine Drug Discovery through Molecular Docking)
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21 pages, 7947 KiB  
Article
In Silico Analysis of USP7 Inhibitors Based on Building QSAR Models and Fragment Design for Screening Marine Compound Libraries
by Huiting Tan, Chenying Li, Tianli Lai and Lianxiang Luo
Mar. Drugs 2024, 22(1), 1; https://doi.org/10.3390/md22010001 - 19 Dec 2023
Viewed by 1588
Abstract
USP7 is highly expressed in a variety of tumors and is thought to play a major role in cancer development. However, there are no drugs available to target USP7, so there is a need to develop new USP7 inhibitors. In this study, AutoQSAR, [...] Read more.
USP7 is highly expressed in a variety of tumors and is thought to play a major role in cancer development. However, there are no drugs available to target USP7, so there is a need to develop new USP7 inhibitors. In this study, AutoQSAR, multiple linear regression, and Naive Bayesian models were constructed using 543 compounds and used to analyze marine compounds. After selecting 240 small molecules for molecular docking with Maestro, MOE, and GOLD, better small molecules than the positive compound P217564 were screened. The molecular structure of “1, 2-dibromobenzene” was optimized to improve the binding effect of the protein, and 10 optimized compounds in ADMET performed well during the screening process. To study the dynamic combination of protein–ligand effect consistency with static molecular docking, 100ns molecular dynamics simulations of candidate compound 1008-1, reference compound P217564, and negative-positive GNE2917 were conducted. The results of molecular docking and molecular dynamics simulation analysis showed that compound 1008-1 maintained a stable conformation with the target protein. Thus, the comprehensive analysis suggests that compound 1008-1 could provide new possibilities for USP7 covalent inhibitor candidates. Full article
(This article belongs to the Special Issue Marine Drug Discovery through Molecular Docking)
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