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Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Therapeutics, 2nd Edition

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 2289

Special Issue Editors


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Guest Editor
Bioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Campus Nueva Granada, Cajicá 250247, Colombia
Interests: natural product chemistry (isolation and structure elucidation); secondary/specialized metabolism; metabolic profiling; molecular modelling; docking and dynamics; bioorganic and medicinal chemistry; anti-parasitic, anti-cancer; anti-fungal; anti-inflammatory bioactive compounds
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Chemistry, Jackson State University, Jackson, MS 39217-0095, USA
Interests: natural products chemistry and chemical biology; drug discovery and target identification for infectious diseases; crop protection, and cancer; chemical proteomics and proteome dynamics; metabolomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Following the first successful Special Issue on this topic (available here), we are happy to announce a second edition titled “Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Therapeutics, 2nd Edition”.

Natural products (NPs) from plants, fungi, and various microorganisms have played very important roles in modern drug discovery. They still do so in the 21st century. An increasing number of highly promising discoveries in this field are published in natural product periodicals such as Molecules every year. This Special Issue within the Natural Products Chemistry Section of Molecules will feature some of the recent and most promising findings in this area.

Original communications may be related to structurally new NPs with exciting potential as hits or lead structures, novel findings on the biological effects and therapeutic potential of previously known natural products, new results on structure–activity relationships and/or mechanisms of action within particularly promising classes of natural products, applications on statistical integration of chemical and biological activity datasets for pattern recognition to determine promising bioactive from mixtures of natural origin, and articles on the fast-growing field of development and application of new strategies and approaches for the discovery of new NPs with bioactivity and therapeutic potential. Last but not least, timely, critical, and comprehensive reviews on particularly interesting topics within the broad field of natural products chemistry and biology are highly welcome.

Please note that a strong focus in this Special Issue will be put on a clear connection between chemical structure and biological/therapeutic effects. Thus, communications on the biological effects of chemically uncharacterized or poorly characterized preparations of “alternative therapeutic systems” or crude extracts/fractions without a clear connection to the underlying chemical principles will not be considered.

Prof. Dr. Ericsson Coy-Barrera
Prof. Dr. Ifedayo Victor Ogungbe
Prof. Dr. Thomas J. Schmidt
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. Molecules is an international peer-reviewed open access semimonthly 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 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

  • drug development from natural products
  • natural hits and leads (including synthetic optimization)
  • mechanism of action
  • therapeutic application
  • structure-activity relationships
  • drug repositioning of natural products
  • new methodologies to isolate and characterize biologically active natural products
  • biosynthesis of natural products-derived drugs
  • innovative production of bioactive natural products by metabolic engineering or in vitro culture
  • compound libraries of bioactive natural products and analogs to support drug discovery
  • open access repository of bioactive natural products’ spectroscopic data for dereplication and identification of hit compounds
  • high-throughput screening and microfractionation to discover bioactive natural products
  • natural products-inspired protein degraders
  • natural product inhibitors of protein-protein interactions
  • natural products-based immunomodulators
  • applications of machine learning (ML) and artificial intelligence (AI) in de novo structure elucidation
  • applications of machine learning (ML) and artificial intelligence (AI) in the discovery of new natural products.

Related Special Issue

Published Papers (2 papers)

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Research

18 pages, 6635 KiB  
Article
In Vitro Anti-Toxoplasma Activity of Extracts Obtained from Tabebuia rosea and Tabebuia chrysantha: The Role of β-Amyrin
by Maria Camila Cardona-Trujillo, Francisco Javier Jiménez-González, Luz Angela Veloza and Juan Carlos Sepúlveda-Arias
Molecules 2024, 29(5), 920; https://doi.org/10.3390/molecules29050920 - 20 Feb 2024
Viewed by 621
Abstract
Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii that is highly prevalent worldwide. Although the infection is asymptomatic in immunocompetent individuals, it severely affects immunocompromised individuals, causing conditions such as encephalitis, myocarditis, or pneumonitis. The limited therapeutic efficacy of drugs [...] Read more.
Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii that is highly prevalent worldwide. Although the infection is asymptomatic in immunocompetent individuals, it severely affects immunocompromised individuals, causing conditions such as encephalitis, myocarditis, or pneumonitis. The limited therapeutic efficacy of drugs currently used to treat toxoplasmosis has prompted the search for new therapeutic alternatives. The aim of this study was to determine the anti-Toxoplasma activity of extracts obtained from two species of the genus Tabebuia. Twenty-six extracts, 12 obtained from Tabebuia chrysantha and 14 from Tabebuia rosea, were evaluated by a colorimetric technique using the RH strain of T. gondii that expresses β-galactosidase. Additionally, the activity of the promising extracts and their active compounds was evaluated by flow cytometry. β-amyrin was isolated from the chloroform extract obtained from the leaves of T. rosea and displayed important anti-Toxoplasma activity. The results show that natural products are an important source of new molecules with considerable biological and/or pharmacological activity. Full article
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24 pages, 7036 KiB  
Article
Machine-Learning- and Structure-Based Virtual Screening for Selecting Cinnamic Acid Derivatives as Leishmania major DHFR-TS Inhibitors
by Maria Camila Muñoz-Vega, Sofía López-Hernández, Adrián Sierra-Chavarro, Marcus Tullius Scotti, Luciana Scotti, Ericsson Coy-Barrera and Chonny Herrera-Acevedo
Molecules 2024, 29(1), 179; https://doi.org/10.3390/molecules29010179 - 28 Dec 2023
Viewed by 1334
Abstract
The critical enzyme dihydrofolate reductase-thymidylate synthase in Leishmania major (LmDHFR-TS) serves a dual-purpose role and is essential for DNA synthesis, a cornerstone of the parasite’s reproductive processes. Consequently, the development of inhibitors against LmDHFR-TS is crucial for the creation of [...] Read more.
The critical enzyme dihydrofolate reductase-thymidylate synthase in Leishmania major (LmDHFR-TS) serves a dual-purpose role and is essential for DNA synthesis, a cornerstone of the parasite’s reproductive processes. Consequently, the development of inhibitors against LmDHFR-TS is crucial for the creation of novel anti-Leishmania chemotherapies. In this study, we employed an in-house database containing 314 secondary metabolites derived from cinnamic acid that occurred in the Asteraceae family. We conducted a combined ligand/structure-based virtual screening to identify potential inhibitors against LmDHFR-TS. Through consensus analysis of both approaches, we identified three compounds, i.e., lithospermic acid (237), diarctigenin (306), and isolappaol A (308), that exhibited a high probability of being inhibitors according to both approaches and were consequently classified as promising hits. Subsequently, we expanded the binding mode examination of these compounds within the active site of the test enzyme through molecular dynamics simulations, revealing a high degree of structural stability and minimal fluctuations in its tertiary structure. The in silico predictions were then validated through in vitro assays to examine the inhibitory capacity of the top-ranked naturally occurring compounds against LmDHFR-TS recombinant protein. The test compounds effectively inhibited the enzyme with IC50 values ranging from 6.1 to 10.1 μM. In contrast, other common cinnamic acid derivatives (i.e., flavonoid glycosides) from the Asteraceae family, such as hesperidin, isovitexin 4′-O-glucoside, and rutin, exhibited low activity against this target. The selective index (SI) for all tested compounds was determined using HsDHFR with moderate inhibitory effect. Among these hits, lignans 306 and 308 demonstrated the highest selectivity, displaying superior SI values compared to methotrexate, the reference inhibitor of DHFR-TS. Therefore, continued research into the anti-leishmanial potential of these C6C3-hybrid butyrolactone lignans may offer a brighter outlook for combating this neglected tropical disease. Full article
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