Current and Recent Advances in Natural Products-Based Drug Discovery, Design and Development

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (28 February 2024) | Viewed by 10987

Special Issue Editors


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Guest Editor
Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
Interests: natural products; medicinal chemistry; biological chemistry; drug design; drug development; organic chemistry; total synthesis; molecular modeling; anti-cancers; neuro-medicines; anti-inflammatory; anti-infectives

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Guest Editor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA
Interests: natural products; cancer therapeutics; thyroid cancer; immunotherapy

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Guest Editor
Department of Food Science and Technology, Agriculture School, Polytechnic Institute of Coimbra, Coimbra, Portugal
Interests: natural products; bioactive ingredients; recovery and extraction processes; antioxidants; antimicrobials
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Special Issue Information

Dear Colleagues,

Natural products have served as a plentiful source of drugs since the old days. The successful story of natural products in the discovery and development of medicines is still being written and forecasted to continue in the future. Not necessarily that the final approved drug is a natural product, but in many cases, it could also be a semi-synthetic compound, a modified derivative, an analog of a natural product, or even a purely synthetic compound that mimics a natural product or inspired by a natural product. In principle, natural products-based drug discovery design and development comprise several steps that involve, but are not limited to:

  • Extraction, isolation, characterization, and biological evaluation of natural products or metabolites.
  • Design, synthesis, and evaluation of synthetic or semi-synthetic derivative or analogs.
  • Development of purely synthetic molecules that mimic natural products.

In addition, natural products-based drug discovery design and development encompass in vitro and/or in silico study of molecular mechanisms and/or target identification, development of synthetic routes to access interesting bioactive natural products, and several other related areas to drug discovery and development.

In this Special Issue, we intend to spotlight the current and significant advances, starting from basic research to clinical development in the hot topic of Natural Products-Based Drug Discovery, Design and Development. Both research and review manuscripts might be considered in this special issue.

Prof. Dr. Ahmed H. E. Hassan
Dr. Rhitajit Sarkar
Prof. Dr. Marta H. Henriques
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 2600 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 discovery of natural products, analogs, derivatives, mimics or related molecules
  • drug design of natural products, analogs, derivatives, mimics or related molecules
  • drug development of natural products, analogs, derivatives, mimics or related molecules
  • bioactive natural products
  • extraction of natural bioactive compounds
  • analogs of natural products
  • derivatives of natural products
  • mimics of natural products
  • bioactivity mechanisms of natural products and related compounds
  • target identification of natural products and related compounds
  • preclinical and/or clinical studies

Published Papers (7 papers)

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Research

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14 pages, 13194 KiB  
Article
Anti-Proliferative and Apoptotic Activities of Rumex crispus
by Sepideh Mohammadhosseinpour, Mukund Bhandari, Dallas A. Lee and Beatrice Clack
Life 2024, 14(1), 8; https://doi.org/10.3390/life14010008 - 20 Dec 2023
Viewed by 893
Abstract
Colorectal cancer is the fourth leading cause of cancer death and the third most common cancer diagnosed in the United States. Several anticancer compounds from natural products have been of great interest in cancer chemotherapy and are currently in clinical trials. Natural products [...] Read more.
Colorectal cancer is the fourth leading cause of cancer death and the third most common cancer diagnosed in the United States. Several anticancer compounds from natural products have been of great interest in cancer chemotherapy and are currently in clinical trials. Natural products that present the targeted killing of cancerous cell and are soluble in water with minimal side effects are ideal candidates. In this study, water-soluble compounds from Rumex crispus plants were screened for anti-proliferative and apoptotic activity against human colorectal adenocarcinoma (DLD-1) cells. The most potent fraction with the highest cell killing and caspase fold change rates was selected for further experiments. The observed changes were further validated by measuring the caspase fold change using RT-qPCR. Furthermore, gene transcript levels were evaluated using an RT2 Profiler assay and a microarray experiment. Our results showed that the most potent L19 fraction exhibits anti-proliferative activity in a dose-dependent manner. The L19 fraction was found to induce apoptotic pathways by triggering different caspases and inflammatory pathways through the activation of non-apoptotic genes. Our study identified and validated the anticancer property of the L19 fraction, which can serve as a strong lead compound for the synthesis of other novel potent analogues. Full article
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16 pages, 3918 KiB  
Article
Stimulation of Hemolysis and Eryptosis by β-Caryophyllene Oxide
by Sumiah A. Alghareeb, Mohammad A. Alfhili and Jawaher Alsughayyir
Life 2023, 13(12), 2299; https://doi.org/10.3390/life13122299 - 4 Dec 2023
Viewed by 1071
Abstract
Background: Eryptosis stimulated by anticancer drugs can lead to anemia in patients. β-caryophyllene oxide (CPO) is an anticancer sesquiterpene present in various plants; however, its effect on the structure and function of human red blood cells (RBCs) remains unexplored. The aim of this [...] Read more.
Background: Eryptosis stimulated by anticancer drugs can lead to anemia in patients. β-caryophyllene oxide (CPO) is an anticancer sesquiterpene present in various plants; however, its effect on the structure and function of human red blood cells (RBCs) remains unexplored. The aim of this study was to investigate the hemolytic and eryptotic activities and underlying molecular mechanisms of CPO in human RBCs. Methods: Cells were treated with 10–100 μM of CPO for 24 h at 37 °C, and hemolysis, LDH, AST, and AChE activities were photometrically assayed. Flow cytometry was employed to determine changes in cell volume from FSC, phosphatidylserine (PS) externalization by annexin-V-FITC, intracellular calcium by Fluo4/AM, and oxidative stress by 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA). Cells were also cotreated with CPO and specific signaling inhibitors and antihemolytic agents. Furthermore, whole blood was exposed to CPO to assess its toxicity to other peripheral blood cells. Results: CPO induced concentration-responsive hemolysis with LDH and AST leakage, in addition to PS exposure, cell shrinkage, Ca2+ accumulation, oxidative stress, and reduced AChE activity. The toxicity of CPO was ameliorated by D4476, staurosporin, and necrosulfonamide. ATP and PEG 8000 protected the cells from hemolysis, while urea and isotonic sucrose had opposite effects. Conclusions: CPO stimulates hemolysis and eryptosis through energy depletion, Ca2+ buildup, oxidative stress, and the signaling mediators casein kinase 1α, protein kinase C, and mixed lineage kinase domain-like pseudokinase. Development of CPO as an anticancer therapeutic must be approached with prudence to mitigate adverse effects on RBCs using eryptosis inhibitors, Ca2+ channel blockers, and antioxidants. Full article
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13 pages, 4866 KiB  
Article
Poria cocos Lanostane Triterpenoids Extract Promotes Collagen and Hyaluronic Acid Production in D-Galactose-Induced Aging Rats
by Chien-Liang Chao, Han-Peng Kuo, Hsin-Wen Huang, Maw-Yeun Cheng, Hsin-Fan Chao, Shih-Min Lu, Hang-Ching Lin, Chao-Jih Wang, Tsu-Chung Chang and Chi-Rei Wu
Life 2023, 13(11), 2130; https://doi.org/10.3390/life13112130 - 28 Oct 2023
Viewed by 1396
Abstract
The global aging population is expanding at an increasingly rapid pace, with approximately one-fourth of the world’s population expected to be composed of elderly individuals by 2050. Aging skin is one of the major characteristics expressed in the elderly. The study comprehensively utilizes [...] Read more.
The global aging population is expanding at an increasingly rapid pace, with approximately one-fourth of the world’s population expected to be composed of elderly individuals by 2050. Aging skin is one of the major characteristics expressed in the elderly. The study comprehensively utilizes both cell and animal experiments to confirm the skin anti-aging effects of Poria cocos (P. cocos), which is one of the most important traditional Chinese medicines classified as tonic Chinese medicine, commonly used to treat physical weakness and aging-associated diseases. We demonstrate in this study that P. cocos lanostane triterpenoids extract (Lipucan®) ameliorates aging skin and promotes collagen accumulation and hyaluronic acid production in galactose-induced aging rats. Purified lanostane triterpenoids were initially identified as active components in P. cocos, which significantly increased collagen and hyaluronic acid levels in cultured human skin cells. Full article
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23 pages, 12009 KiB  
Article
In Silico Exploration and Experimental Validation of Camellia sinensis Extract against Rhipicephalus microplus and Sarcoptes scabiei: An Integrated Approach
by Mohammed Ageeli Hakami, Nosheen Malak, Afshan Khan, Hidayat Ullah, Raquel Cossío-Bayúgar, Nasreen Nasreen, Sadaf Niaz, Adil Khan and Chien-Chin Chen
Life 2023, 13(10), 2040; https://doi.org/10.3390/life13102040 - 11 Oct 2023
Viewed by 1054
Abstract
Sarcoptes scabiei is an ectoparasite of humans and animals that causes scabies. The Rhipicephalus (Boophilus) microplus is a blood-sucking ectoparasite that transmits various pathogens. These two parasites have caused great losses to a country’s dairy and agriculture sectors. The aim of this study [...] Read more.
Sarcoptes scabiei is an ectoparasite of humans and animals that causes scabies. The Rhipicephalus (Boophilus) microplus is a blood-sucking ectoparasite that transmits various pathogens. These two parasites have caused great losses to a country’s dairy and agriculture sectors. The aim of this study was to determine the in vitro and in silico efficacy of Camellia sinensis plant extracts. Different concentrations of C. sinensis ethanolic plant extracts were prepared using the maceration method and were used against mites and ticks (in adult immersion test AIT and larval packet test LPT) to evaluate their in vitro acaricidal activity. Additionally, in silico molecular docking was performed to investigate the inhibitory interactions between the phytochemicals of the plant and S. scabiei and R. microplus glutathione transferase proteins (SsGST and RmGST). This study observed that the plant extract showed high efficacy in vitro against mites and different tick stages in adult immersion and larval packet tests. Additionally, the in silico study revealed a strong binding interaction between ellagic acid and SsGST protein, with a binding energy of −7.3 kcal/mol, with respect to permethrin (−6.7 kcal/mol), whereas quercetin and RmGST resulted in a docking score of −8.6 kcal/mol compared to deltamethrin (−8.2 kcal/mol). Overall, this study explored the potential of C. sinensis as a natural alternative for controlling tick and mite infestations and provided insights into the inhibitory mechanisms of its phytochemicals. Full article
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19 pages, 4579 KiB  
Article
In Silico and In Vitro Studies of Novel Azomethines on DNA Repair Genes in Gastric Cell Lines
by Alpaslan Ozturk, Tugba Agbektas, Alakbar Huseynzada, Ruslan Guliyev, Rana Ganbarova, Ulviyya Hasanova, Ayca Tas, Sultan Erkan, Cemile Zontul, Nihal Inandiklioglu and Yavuz Silig
Life 2023, 13(10), 1982; https://doi.org/10.3390/life13101982 - 28 Sep 2023
Viewed by 1118
Abstract
We herein report the determination of the cytotoxic activity and expression profiles of some DNA repair genes of newly synthesized azomethines in the gastric cancer cell line (AGS). The studied novel compounds were synthesized by a condensation reaction and received compounds were characterized [...] Read more.
We herein report the determination of the cytotoxic activity and expression profiles of some DNA repair genes of newly synthesized azomethines in the gastric cancer cell line (AGS). The studied novel compounds were synthesized by a condensation reaction and received compounds were characterized by 1H and 13C NMR spectroscopy methods. Furthermore, they were applied to the AGS cell line at eight different concentrations (0.1–50 µg/mL). Anticancer activities were determined using the MTT method. Expression levels of ATR, ERCC1, TOP2A, and ABCB1 genes were determined by the RT-PCR method. Biochemical parameters were also examined. The interaction of proteins with other proteins was investigated with the String v11 program. The IC50 values of compounds 1, 2, and 3 obtained after 72 h were 23.10, 8.93, and 1.58 µg/mL, respectively. The results demonstrate that the cytotoxic activity of compound 3 on AGS cancer cells is higher in comparison with other molecules. It was determined that the expression levels of ATR, TOP2A, and ABCB1 genes in compounds 1, 2, and 3 were decreased compared to the control group. In addition, it was determined that ERCC1 gene expression increased in compound 3, decreased in compound 2, and remained unchanged in compound 1 (p < 0.001). In AGS gastric cancer cells, a 64% decrease was detected for GST levels in compound 1, while a 38% decrease in GSH levels in compound 2. In addition, compounds 1–3 were examined at the molecular level with computational techniques and the docking studies revealed 4LN0 as a target protein. Full article
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Review

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19 pages, 2066 KiB  
Review
Therapeutic Potential of Myrtenal and Its Derivatives—A Review
by Stela Dragomanova, Velichka Andonova, Konstantin Volcho, Nariman Salakhutdinov, Reni Kalfin and Lyubka Tancheva
Life 2023, 13(10), 2086; https://doi.org/10.3390/life13102086 - 20 Oct 2023
Cited by 2 | Viewed by 1330
Abstract
The investigation of monoterpenes as natural products has gained significant attention in the search for new pharmacological agents due to their ability to exhibit a wide range in biological activities, including antifungal, antibacterial, antioxidant, anticancer, antispasmodic, hypotensive, and vasodilating properties. In vitro and [...] Read more.
The investigation of monoterpenes as natural products has gained significant attention in the search for new pharmacological agents due to their ability to exhibit a wide range in biological activities, including antifungal, antibacterial, antioxidant, anticancer, antispasmodic, hypotensive, and vasodilating properties. In vitro and in vivo studies reveal their antidepressant, anxiolytic, and memory-enhancing effects in experimental dementia and Parkinson’s disease. Chemical modification of natural substances by conjugation with various synthetic components is a modern method of obtaining new biologically active compounds. The discovery of new potential drugs among monoterpene derivatives is a progressive avenue within experimental pharmacology, offering a promising approach for the therapy of diverse pathological conditions. Biologically active substances such as monoterpenes, for example, borneol, camphor, geraniol, pinene, and thymol, are used to synthesize compounds with analgesic, anti-inflammatory, anticonvulsive, antidepressant, anti-Alzheimer’s, antiparkinsonian, antiviral and antibacterial (antituberculosis) properties. Myrtenal is a perspective monoterpenoid with therapeutic potential in various fields of medicine. Its chemical modifications often lead to new or more pronounced biological effects. As an example, the conjugation of myrtenal with the established pharmacophore adamantane enables the augmentation of several of its pivotal properties. Myrtenal–adamantane derivatives exhibited a variety of beneficial characteristics, such as antimicrobial, antifungal, antiviral, anticancer, anxiolytic, and neuroprotective properties, which are worth examining in more detail and at length. Full article
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25 pages, 1711 KiB  
Review
The Role of Mitochondrial Dysfunction in Alzheimer’s: Molecular Defects and Mitophagy-Enhancing Approaches
by Reem M. Farsi
Life 2023, 13(4), 970; https://doi.org/10.3390/life13040970 - 8 Apr 2023
Cited by 1 | Viewed by 2566
Abstract
Alzheimer’s disease (AD), a progressive and chronic neurodegenerative syndrome, is categorized by cognitive and memory damage caused by the aggregations of abnormal proteins, specifically including Tau proteins and β-amyloid in brain tissue. Moreover, mitochondrial dysfunctions are the principal causes of AD, which is [...] Read more.
Alzheimer’s disease (AD), a progressive and chronic neurodegenerative syndrome, is categorized by cognitive and memory damage caused by the aggregations of abnormal proteins, specifically including Tau proteins and β-amyloid in brain tissue. Moreover, mitochondrial dysfunctions are the principal causes of AD, which is associated with mitophagy impairment. Investigations exploring pharmacological therapies alongside AD have explicitly concentrated on molecules accomplished in preventing/abolishing the gatherings of the abovementioned proteins and mitochondria damages. Mitophagy is the removal of dead mitochondria by the autophagy process. Damages in mitophagy, the manner of diversified mitochondrial degeneracy by autophagy resulting in an ongoing aggregation of malfunctioning mitochondria, were also suggested to support AD. Recently, plentiful reports have suggested a link between defective mitophagy and AD. This treaty highlights updated outlines of modern innovations and developments on mitophagy machinery dysfunctions in AD brains. Moreover, therapeutic and nanotherapeutic strategies targeting mitochondrial dysfunction are also presented in this review. Based on the significant role of diminished mitophagy in AD, we suggest that the application of different therapeutic approaches aimed at stimulating mitophagy in AD would be beneficial for targeting or reducing the mitochondrial dysfunction induced by AD. Full article
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