Submit to Molecules Review for Molecules Propose a Special Issue

Journal Menu

Journal Browser

50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Related Special Issue
Published Papers

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 2022) | Viewed by 27291

Share This Special Issue

Special Issue Editors

Dr. Valeria Patricia Sülsen

E-Mail Website
Guest Editor

1. Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
2. Institute of Chemistry and Metabolism of Drugs (IQUIMEFA), University of Buenos Aires—National Scientific and Technical Research Council, Buenos Aires, Argentina
Interests: neglected diseases; antimicrobial activity; natural compounds; plant extracts; terpenoids; flavonoids; Asteraceae
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Marcus Tullius Scotti

E-Mail Website
Guest Editor

Department of Chemistry, Federal University of Paraíba, João Pessoa, Brazil
Interests: natural products database; cheminformatics; virtual screening; chemotaxonomy; natural product drug discovery; machine learning; molecular descriptors
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. William N. Setzer

E-Mail Website
Guest Editor

Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL, USA
Interests: natural product drug discovery; phytochemistry; essential oils; chemical ecology; molecular modeling
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Bing Zhou

E-Mail Website
Guest Editor

School of life sciences, Tsinghua University, Beijing, China
Interests: mode of action of artemisinin; iron/zinc homeostasis and its relevance to diseases

Special Issue Information

Dear Colleagues,

Natural products have played an important role in drug discovery processes. Many natural compounds and their derivatives are used for the treatment of different maladies. Among them, and regarding antiparasitic compounds isolated from natural sources, artemisinin stands out. The discovery of this sesquiterpene lactone and its application for the treatment of malaria led to the Nobel Prize in Medicine being awarded to Dr. Youyou Tu in 2015. Artemisinin has been isolated from the medicinal plant Artemisia annua (Asteraceae), also known as qinghao, which has been used for years as febrifuge in China. This compound is a cadinanolide-type sesquiterpene lactone with an endoperoxide ring in its structure. Artemisinin-based drugs are used today for chloroquine-resistant Plasmodium falciparum malaria. This compound or its analogues have also been active against other parasites, such as Trypanosoma spp., Leishmania spp., and Echinococcus spp., among others. Artemisinin and its derivatives have also shown anticancer potential due to their capacity to inhibit cell growth and to induce apoptosis in tumor cell lines. Some of them are in clinical trials for breast and colorectal cancer.

This Special Issue is dedicated to the 50th anniversary of artemisinin, a fascinating molecule that has changed the world and has highlighted the role of natural compounds in the drug discovery process. Similar to artemisinin, other sesquiterpene lactones and natural compounds could be promising candidates for the development of new medicines.

This Special Issue will focus on bioactive natural compounds as potential leads for the treatment of neglected diseases. Research papers dealing with natural compounds as well as semisynthetic derivatives with activity against causative agents of neglected diseases will be considered. Other infectious diseases having consequences in public health and of high relevance worldwide will also be included.

Prof. Dr. Valeria Sülsen
Prof. Dr. Marcus Tullius Scotti
Prof. Dr. William N. Setzer
Prof. Dr. Bing Zhou
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

natural compounds
semisynthetic derivatives
neglected diseases

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Related Special Issue

Natural Products as Leads or Drugs against Neglected Tropical Diseases in Molecules (94 articles)

Published Papers (11 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Editorial

Jump to: Research

1 pages, 154 KiB

Open AccessEditorial

Special Issue “Artemisinin (Qinghaosu): Commemorative Issue in Honor of Professor Youyou Tu on the Occasion of Her 80th Anniversary” in International Molecules Published in 2010

by Yan He and Shu-Kun Lin

Molecules 2021, 26(2), 279; https://doi.org/10.3390/molecules26020279 - 8 Jan 2021

Cited by 1 | Viewed by 1962

Abstract

It has been more than 10 years since we published the Special Issue “Artemisinin (Qinghaosu): commemorative issue in honor of Professor Youyou Tu on the occasion of her 80th anniversary” (Abbreviated as “the Artemisinins Special Issue”) [...] Full article

(This article belongs to the Special Issue 50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents)

Research

Jump to: Editorial

7 pages, 1297 KiB

Open AccessCommunication

In Vitro Efficacy of Terpenes from Essential Oils against Sarcoptes scabiei

by Meilin Li, Shenrui Feng, Siyi Huang, Jacques Guillot and Fang Fang

Molecules 2023, 28(8), 3361; https://doi.org/10.3390/molecules28083361 - 11 Apr 2023

Cited by 2 | Viewed by 2133

Abstract

The mite Sarcoptes scabiei is responsible for the emerging or re-emerging skin disease called scabies in humans and sarcoptic mange in animals. Essential oils represent an appealing alternative strategy for the control of Sarcoptes infections, but the commercial development of essential oils may be hampered by their inconsistency in efficacy due to their varied chemical compositions. In order to address this issue, we assessed the efficacy of six components (carvacrol, eugenol, geraniol, citral, terpinen-4-ol, and linalool) against S. scabiei. At a concentration of 0.5%, carvacrol presented the best miticidal efficacy, with a median lethal time (LT₅₀) value of 6.7 min, followed by eugenol (56.3 min), geraniol (1.8 h), citral (6.1 h), terpinen-4-ol (22.3 h), and linalool (39.9 h). The LC₅₀ values at 30 min for carvacrol, eugenol, and geraniol were 0.24, 0.79, and 0.91%, respectively. In conclusion, carvacrol, eugenol, and geraniol represent potential complementary or alternative agents for S. scabiei infections in humans or animals. Our study provides a scientific basis for the development of scabicidal products based on essential oils. Full article

(This article belongs to the Special Issue 50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents)

► Show Figures

Figure 1

13 pages, 5220 KiB

Open AccessArticle

A Composition Analysis and an Antibacterial Activity Mechanism Exploration of Essential Oil Obtained from Artemisia giraldii Pamp

by Guiguo Huo, Xu Li, Mohamed Aamer Abubaker, Tingyu Liang, Ji Zhang and Xuelin Chen

Molecules 2022, 27(21), 7300; https://doi.org/10.3390/molecules27217300 - 27 Oct 2022

Cited by 3 | Viewed by 1682

Abstract

The goal of this work was to use the GC-MS technique to explore the chemical components of Artemisia giraldii Pamp essential oil (AgEo) and to uncover its antibacterial activity, specifically the antibacterial mechanism of this essential oil. There were a total of 63 chemical constituents in the AgEo, monoterpenes (10.2%) and sesquiterpenes (30.14%) were found to be the most common chemical components, with camphor (15.68%) coming in first, followed by germacrene D. (15.29%). AgEo displayed significant reducing power and good scavenging ability on hydroxyl radicals, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals, and 2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate (ABTS) radicals, according to antioxidant data. The diameter of the inhibition zone (DIZ) of AgEo against S. aureus and E. coli was (14.00 ± 1.00) mm and (16.33 ± 1.53) mm, respectively; the minimum inhibitory concentration (MIC) of AgEo against E. coli and S. aureus was 3 μL/mL and 6 μL/mL, respectively; and the minimum bactericidal concentration (MBC) of AgEo against E. coli and S. aureus was 6 μL/mL and 12 μL/mL, respectively. The antibacterial curve revealed that 0.5MIC of AgEo may delay bacterial growth while 2MIC of AgEo could totally suppress bacterial growth. The relative conductivity, alkaline phosphatase (AKP) activity, and protein concentration of the bacterial suspension were all higher after the AgEo treatment than in the control group, and increased as the essential oil concentration was raised. In addition, the cell membrane ruptured and atrophy occurred. The study discovered that AgEo is high in active chemicals and can be used as an antibacterial agent against E. coli and S. aureus, which is critical for AgEo’s future research and development. Full article

(This article belongs to the Special Issue 50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents)

► Show Figures

Figure 1

17 pages, 4710 KiB

Open AccessArticle

Structural Basis of Artemisinin Binding Sites in Serum Albumin with the Combined Use of NMR and Docking Calculations

by Alexandra Primikyri, Georgios Papamokos, Themistoklis Venianakis, Marianna Sakka, Vassiliki G. Kontogianni and Ioannis P. Gerothanassis

Molecules 2022, 27(18), 5912; https://doi.org/10.3390/molecules27185912 - 12 Sep 2022

Cited by 6 | Viewed by 2233

Abstract

Artemisinin is known to bind to the main plasma protein carrier serum albumin (SA); however, there are no atomic level structural data regarding its binding mode with serum albumin. Herein, we employed a combined strategy of saturation transfer difference (STD), transfer nuclear Overhauser effect spectroscopy (TR-NOESY), STD–total correlation spectroscopy (STD-TOCSY), and Interligand Noes for PHArmacophore Mapping (INPHARMA) NMR methods and molecular docking calculations to investigate the structural basis of the interaction of artemisinin with human and bovine serum albumin (HSA/BSA). A significant number of inter-ligand NOEs between artemisinin and the drugs warfarin and ibuprofen as well as docking calculations were interpreted in terms of competitive binding modes of artemisinin in the warfarin (FA7) and ibuprofen (FA4) binding sites. STD NMR experiments demonstrate that artemisinin is the main analyte for the interaction of the A. annua extract with BSA. The combined strategy of NMR and docking calculations of the present work could be of general interest in the identification of the molecular basis of the interactions of natural products with their receptors even within a complex crude extract. Full article

(This article belongs to the Special Issue 50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents)

► Show Figures

Figure 1

18 pages, 2092 KiB

Open AccessArticle

Assay Development and Identification of the First Plasmodium falciparum 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase Inhibitors

by Marie Hoarau, Nattida Suwanakitti, Thaveechai Varatthan, Ratthiya Thiabma, Roonglawan Rattanajak, Netnapa Charoensetakul, Emily K. Redman, Tanatorn Khotavivattana, Tirayut Vilaivan, Yongyuth Yuthavong and Sumalee Kamchonwongpaisan

Molecules 2022, 27(11), 3515; https://doi.org/10.3390/molecules27113515 - 30 May 2022

Cited by 1 | Viewed by 2237

Abstract

In the fight towards eradication of malaria, identifying compounds active against new drug targets constitutes a key approach. Plasmodium falciparum 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (PfHPPK) has been advanced as a promising target, as being part of the parasite essential folate biosynthesis pathway while having no orthologue in the human genome. However, no drug discovery efforts have been reported on this enzyme. In this study, we conducted a three-step screening of our in-house antifolate library against PfHPPK using a newly designed PfHPPK-GFP protein construct. Combining virtual screening, differential scanning fluorimetry and enzymatic assay, we identified 14 compounds active against PfHPPK. Compounds’ binding modes were investigated by molecular docking, suggesting competitive binding with the HMDP substrate. Cytotoxicity and in vitro ADME properties of hit compounds were also assessed, showing good metabolic stability and low toxicity. The most active compounds displayed low micromolar IC₅₀ against drug-resistant parasites. The reported hit compounds constitute a good starting point for inhibitor development against PfHPPK, as an alternative approach to tackle the malaria parasite. Full article

(This article belongs to the Special Issue 50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents)

► Show Figures

Graphical abstract

15 pages, 2171 KiB

Open AccessArticle

The Antagonizing Role of Heme in the Antimalarial Function of Artemisinin: Elevating Intracellular Free Heme Negatively Impacts Artemisinin Activity in Plasmodium falciparum

by Pan Zhu and Bing Zhou

Molecules 2022, 27(6), 1755; https://doi.org/10.3390/molecules27061755 - 8 Mar 2022

Cited by 6 | Viewed by 2317

Abstract

The rich source of heme within malarial parasites has been considered to underly the action specificity of artemisinin. We reasoned that increasing intraparasitic free heme levels might further sensitize the parasites to artemisinin. Various means, such as modulating heme synthesis, degradation, polymerization, or hemoglobin digestion, were tried to boost intracellular heme levels, and under several scenarios, free heme levels were significantly augmented. Interestingly, all results arrived at the same conclusion, i.e., elevating heme acted in a strongly negative way, impacting the antimalarial action of artemisinin, but exerted no effect on several other antimalarial drugs. Suppression of the elevated free heme level by introducing heme oxygenase expression effectively restored artemisinin potency. Consistently, zinc protoporphyrin IX/zinc mesoporphyrin, as analogues of heme, drastically increased free heme levels and, concomitantly, the EC₅₀ values of artemisinin. We were unable to effectively mitigate free heme levels, possibly due to an unknown compensating heme uptake pathway, as evidenced by our observation of efficient uptake of a fluorescent heme homologue by the parasite. Our results thus indicate the existence of an effective and mutually compensating heme homeostasis network in the parasites, including an uncharacterized heme uptake pathway, to maintain a certain level of free heme and that augmentation of the free heme level negatively impacts the antimalarial action of artemisinin. Importance: It is commonly believed that heme is critical in activating the antimalarial action of artemisinins. In this work, we show that elevating free heme levels in the malarial parasites surprisingly negatively impacts the action of artemisinin. We tried to boost free heme levels with various means, such as by modulating heme synthesis, heme polymerization, hemoglobin degradation and using heme analogues. Whenever we saw elevation of free heme levels, reduction in artemisinin potency was also observed. The homeostasis of heme appears to be complex, as there exists an unidentified heme uptake pathway in the parasites, nullifying our attempts to effectively reduce intraparasitic free heme levels. Our results thus indicate that too much heme is not good for the antimalarial action of artemisinins. This research can help us better understand the biological properties of this mysterious drug. Full article

(This article belongs to the Special Issue 50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents)

► Show Figures

Figure 1

17 pages, 2676 KiB

Open AccessArticle

Discovery of Novel Cyclic Ethers with Synergistic Antiplasmodial Activity in Combination with Valinomycin

by Daniel J. Watson, Paul R. Meyers, Kojo Sekyi Acquah, Godwin A. Dziwornu, Christopher Bevan Barnett and Lubbe Wiesner

Molecules 2021, 26(24), 7494; https://doi.org/10.3390/molecules26247494 - 10 Dec 2021

Cited by 3 | Viewed by 2325

Abstract

With drug resistance threatening our first line antimalarial treatments, novel chemotherapeutics need to be developed. Ionophores have garnered interest as novel antimalarials due to their theorized ability to target unique systems found in the Plasmodium-infected erythrocyte. In this study, during the bioassay-guided fractionation of the crude extract of Streptomyces strain PR3, a group of cyclodepsipeptides, including valinomycin, and a novel class of cyclic ethers were identified and elucidated. Further study revealed that the ethers were cyclic polypropylene glycol (cPPG) oligomers that had leached into the bacterial culture from an extraction resin. Molecular dynamics analysis suggests that these ethers are able to bind cations such as K⁺, NH₄⁺ and Na⁺. Combination studies using the fixed ratio isobologram method revealed that the cPPGs synergistically improved the antiplasmodial activity of valinomycin and reduced its cytotoxicity in vitro. The IC₅₀ of valinomycin against P. falciparum NF54 improved by 4–5-fold when valinomycin was combined with the cPPGs. Precisely, it was improved from 3.75 ± 0.77 ng/mL to 0.90 ± 0.2 ng/mL and 0.75 ± 0.08 ng/mL when dosed in the fixed ratios of 3:2 and 2:3 of valinomycin to cPPGs, respectively. Each fixed ratio combination displayed cytotoxicity (IC₅₀) against the Chinese Hamster Ovary cell line of 57–65 µg/mL, which was lower than that of valinomycin (12.4 µg/mL). These results indicate that combinations with these novel ethers may be useful in repurposing valinomycin into a suitable and effective antimalarial. Full article

(This article belongs to the Special Issue 50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents)

► Show Figures

Figure 1

10 pages, 1651 KiB

Open AccessArticle

Quantitative Structure–Activity Relationships of Natural-Product-Inspired, Aminoalkyl-Substituted 1-Benzopyrans as Novel Antiplasmodial Agents

by Friederike M. Wunsch, Bernhard Wünsch, Freddy A. Bernal and Thomas J. Schmidt

Molecules 2021, 26(17), 5249; https://doi.org/10.3390/molecules26175249 - 30 Aug 2021

Cited by 3 | Viewed by 2062

Abstract

On the basis of the finding that various aminoalkyl-substituted chromene and chromane derivatives possess strong and highly selective in vitro bioactivity against Plasmodium falciparum, the pathogen responsible for tropical malaria, we performed a structure–activity relationship study for such compounds. With structures and activity data of 52 congeneric compounds from our recent studies, we performed a three-dimensional quantitative structure–activity relationship (3D-QSAR) study using the comparative molecular field analysis (CoMFA) approach as implemented in the Open3DQSAR software. The resulting model displayed excellent internal and good external predictive power as well as good robustness. Besides insights into the molecular interactions and structural features influencing the antiplasmodial activity, this model now provides the possibility to predict the activity of further untested compounds to guide our further synthetic efforts to develop even more potent antiplasmodial chromenes/chromanes. Full article

(This article belongs to the Special Issue 50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents)

► Show Figures

Figure 1

17 pages, 3709 KiB

Open AccessArticle

Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha

by Sheila C. Araujo, Fernanda S. Sousa, Thais A. Costa-Silva, Andre G. Tempone, João Henrique G. Lago and Kathia M. Honorio

Molecules 2021, 26(14), 4116; https://doi.org/10.3390/molecules26144116 - 6 Jul 2021

Cited by 1 | Viewed by 2307

Abstract

In the present study, the phytochemical study of the n-hexane extract from flowers of Nectandra leucantha (Lauraceae) afforded six known neolignans (1–6) as well as one new metabolite (7), which were characterized by analysis of NMR, IR, UV, and ESI-HRMS data. The new compound 7 exhibited potent activity against the clinically relevant intracellular forms of T. cruzi (amastigotes), with an IC₅₀ value of 4.3 μM and no observed mammalian cytotoxicity in fibroblasts (CC₅₀ > 200 μM). Based on the results obtained and our previous antitrypanosomal data of 50 natural and semi-synthetic related neolignans, 2D and 3D molecular modeling techniques were employed to help the design of new neolignan-based compounds with higher activity. The results obtained from the models were important to understand the main structural features related to the biological response of the neolignans and to aid in the design of new neolignan-based compounds with better biological activity. Therefore, the results acquired from phytochemical, biological, and in silico studies showed that the integration of experimental and computational techniques consists of a powerful tool for the discovery of new prototypes for development of new drugs to treat CD. Full article

(This article belongs to the Special Issue 50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents)

► Show Figures

Figure 1

8 pages, 1383 KiB

Open AccessArticle

Antiplasmodial and Cytotoxic Flavonoids from Pappea capensis (Eckl. & Zeyh.) Leaves

by Nasir Tajuddeen, Tarryn Swart, Heinrich C. Hoppe and Fanie R. van Heerden

Molecules 2021, 26(13), 3875; https://doi.org/10.3390/molecules26133875 - 25 Jun 2021

Cited by 11 | Viewed by 2531

Abstract

Ethnobotanical surveys indicate that the Masai and Kikuyu in Kenya, the Venda in South Africa, and the Gumuz people of Ethiopia use Pappea capensis for the treatment of malaria. The present study aimed to investigate the phytochemical and antiplasmodial properties of the plant leaves. The bioactive compounds were isolated using chromatographic techniques. The structures were established using NMR, HRMS, and UV spectroscopy. Antiplasmodial activity of P. capensis leaf extract and isolated compounds against chloroquine-sensitive 3D7 P. falciparum was evaluated using the parasite lactate dehydrogenase assay. Cytotoxicity against HeLa (human cervix adenocarcinoma) cells was determined using the resazurin assay. The extract inhibited the viability of Plasmodium falciparum by more than 80% at 50 µg/mL, but it was also cytotoxic against HeLa cells at the same concentration. Chromatographic purification of the extract led to the isolation of four flavonoid glycosides and epicatechin. The compounds displayed a similar activity pattern with the extract against P. falciparum and HeLa cells. The results from this study suggest that the widespread use of P. capensis in traditional medicine for the treatment of malaria might have some merits. However, more selectivity studies are needed to determine whether the leaf extract is cytotoxic against noncancerous cells. Full article

(This article belongs to the Special Issue 50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents)

► Show Figures

Figure 1

23 pages, 2147 KiB

Open AccessArticle

Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I

by Chonny Herrera-Acevedo, Areli Flores-Gaspar, Luciana Scotti, Francisco Jaime Bezerra Mendonça-Junior, Marcus Tullius Scotti and Ericsson Coy-Barrera

Molecules 2021, 26(11), 3076; https://doi.org/10.3390/molecules26113076 - 21 May 2021

Cited by 13 | Viewed by 3512

Abstract

The current treatments against Leishmania parasites present high toxicity and multiple side effects, which makes the control and elimination of leishmaniasis challenging. Natural products constitute an interesting and diverse chemical space for the identification of new antileishmanial drugs. To identify new drug options, an in-house database of 360 kauranes (tetracyclic diterpenes) was generated, and a combined ligand- and structure-based virtual screening (VS) approach was performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes were employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay. The half-maximal inhibitory concentration (IC₅₀) values of selected bioactive compounds were examined using the random forest (RF) model (i.e., 2β-hydroxy-menth-6-en-5β-yl ent-kaurenoate (135) and 3α-cinnamoyloxy-ent-kaur-16-en-19-oic acid (302)) were below 10 μM. A compound similar to 302, 3α-p-coumaroyloxy-ent-kaur-16-en-19-oic acid (302a), was also synthesized and showed the highest activity against LmPTR1. Finally, molecular docking calculations and molecular dynamics simulations were performed for the VS-selected, most-active kauranes within the active sites of PTR1 hybrid models, generated from three Leishmania species that are known to cause cutaneous leishmaniasis in the new world (i.e., L. braziliensis, L. panamensis, and L. amazonensis) to explore the targeting potential of these kauranes to other species-dependent variants of this enzyme. Full article

(This article belongs to the Special Issue 50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents)

► Show Figures

Journal Menu

Journal Browser

50th Anniversary Issue of Artemisinin: The Successful Use of Natural Products against Parasitic Agents

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Related Special Issue

Published Papers (11 papers)

Editorial

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI