Emerging Therapeutic Potential of Marine Dinoflagellate Natural Products

: Inflammatory bowel disease (IBD) is a chronic, elusive disorder resulting in relapsing inflammation of intestine with incompletely elucidated etiology, whose two representative forms are ulcerative colitis (UC) and Crohn’s disease (CD). Accumulating researches have revealed that the individual genetic susceptibility, environmental risk elements, intestinal microbial flora, as well as innate and adaptive immune system are implicated in the pathogenesis and development of IBD. Despite remarkable progression of IBD therapy has been achieved by chemical drugs and biological therapies such as aminosalicylates, corticosteroids, antibiotics, anti-tumor necrosis factor (TNF)-α, anti-integrin agents, etc., healing outcome still cannot be obtained, along with inevitable side effects. Consequently, a variety of researches have focused on exploring new therapies, and found that natural products (NPs) isolated from herbs or plants may serve as promising therapeutic agents for IBD through antiinflammatory, anti-oxidant, anti-fibrotic and anti-apoptotic effects, which implicates the modulation on nucleotide- binding domain (NOD) like receptor protein (NLRP) 3 inflammasome, gut microbiota, intestinal microvascular endothelial cells, intestinal epithelia, immune system, etc. In the present review, we will summarize the research development of IBD pathogenesis and current mainstream therapy, as well as the therapeutic potential and intrinsic mechanisms of NPs in IBD.

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A Molecular Modeling Approach to Identify Potential Antileishmanial Compounds Against the Cell Division Cycle (cdc)-2-Related Kinase 12 (CRK12) Receptor of Leishmania donovani

Biomolecules ◽

10.3390/biom11030458 ◽

2021 ◽

Vol 11 (3) ◽

pp. 458

Author(s):

Emmanuel Broni ◽

Samuel K. Kwofie ◽

Seth O. Asiedu ◽

Whelton A. Miller ◽

Michael D. Wilson

Keyword(s):

Natural Products ◽

Cell Division ◽

Leishmania Donovani ◽

Therapeutic Potential ◽

Neglected Tropical Diseases ◽

Binding Pocket ◽

Cell Division Cycle ◽

World Health ◽

Atp Binding ◽

African Flora

The huge burden of leishmaniasis caused by the trypanosomatid protozoan parasite Leishmania is well known. This illness was included in the list of neglected tropical diseases targeted for elimination by the World Health Organization. However, the increasing evidence of resistance to existing antimonial drugs has made the eradication of the disease difficult to achieve, thus warranting the search for new drug targets. We report here studies that used computational methods to identify inhibitors of receptors from natural products. The cell division cycle-2-related kinase 12 (CRK12) receptor is a plausible drug target against Leishmania donovani. This study modelled the 3D molecular structure of the L. donovani CRK12 (LdCRK12) and screened for small molecules with potential inhibitory activity from African flora. An integrated library of 7722 African natural product-derived compounds and known inhibitors were screened against the LdCRK12 using AutoDock Vina after performing energy minimization with GROMACS 2018. Four natural products, namely sesamin (NANPDB1649), methyl ellagic acid (NANPDB1406), stylopine (NANPDB2581), and sennecicannabine (NANPDB6446) were found to be potential LdCRK12 inhibitory molecules. The molecular docking studies revealed two compounds NANPDB1406 and NANPDB2581 with binding affinities of −9.5 and −9.2 kcal/mol, respectively, against LdCRK12 which were higher than those of the known inhibitors and drugs, including GSK3186899, amphotericin B, miltefosine, and paromomycin. All the four compounds were predicted to have inhibitory constant (Ki) values ranging from 0.108 to 0.587 μM. NANPDB2581, NANPDB1649 and NANPDB1406 were also predicted as antileishmanial with Pa and Pi values of 0.415 and 0.043, 0.391 and 0.052, and 0.351 and 0.071, respectively. Molecular dynamics simulations coupled with molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) computations reinforced their good binding mechanisms. Most compounds were observed to bind in the ATP binding pocket of the kinase domain. Lys488 was predicted as a key residue critical for ligand binding in the ATP binding pocket of the LdCRK12. The molecules were pharmacologically profiled as druglike with inconsequential toxicity. The identified molecules have scaffolds that could form the backbone for fragment-based drug design of novel leishmanicides but warrant further studies to evaluate their therapeutic potential.

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Crocus sativus L. Extract and Its Constituents: Chemistry, Pharmacology and Therapeutic Potential

Molecules ◽

10.3390/molecules26144226 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4226

Author(s):

Nikolaos Pitsikas ◽

Konstantinos Dimas

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Organic Compounds ◽

Therapeutic Potential ◽

Crocus Sativus ◽

Natural Sources ◽

Crocus Sativus L

Natural products or organic compounds isolated from natural sources as primary or secondary metabolites have inspired numerous drugs [...]

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Natural products targeting cancer stem cells: a revisit

Current Medicinal Chemistry ◽

10.2174/0929867328666210405111913 ◽

2021 ◽

Vol 28 ◽

Author(s):

Jiahua Cui ◽

Jiajun Qian ◽

Larry Ming-Cheung Chow ◽

Jinping Jia

Keyword(s):

Stem Cells ◽

Drug Resistance ◽

Natural Products ◽

Cancer Stem Cells ◽

Therapeutic Potential ◽

Tumor Development ◽

Biologically Active ◽

Cellular Targets ◽

Drug Candidates ◽

Enhanced Expression

Background: The proposed central role of cancer stem cells (CSCs) in tumor development has been extended to explain the diverse oncologic phenomena such as multidrug resistance, metastasis and tumor recurrence in clinics. Due to the enhanced expression of ATP-binding cassette transporters and anti-apoptotic factors, stagnation on G0 phase and the strong ability of self-renewal, the CSCs were highly resistant to clinical anticancer drugs. Therefore, the discovery of new drug candidates that could effectively eradicate cancer stem cells afforded promising outcomes in cancer therapy. Introduction: Natural products and their synthetic analogues are a rich source of biologically active compounds and several of them have already been recognized as potent CSCs killers. We aim to provide a collection of recently identified natural products that suppressed the survival of the small invasive CSC populations and combated the drug resistance of these cells in chemotherapy. Results and Conclusion: These anti-CSCs natural products included flavonoids, stilbenes, quinones, terpenoids, polyketide antibiotics, steroids and alkaloids. In the present review, we highlighted the therapeutic potential of natural products and their derivatives against the proliferation and drug resistance of CSCs, their working mechanisms and related structure-activity relationships. Meanwhile, in this survey, several natural products with diverse cellular targets such as the naphthoquinone shikonin and the stilbene resveratrol were characterized as promising lead compounds for future development.

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Natural products with therapeutic potential in melanoma metastasis

Natural Product Reports ◽

10.1039/c4np00130c ◽

2015 ◽

Vol 32 (8) ◽

pp. 1170-1182 ◽

Cited By ~ 41

Author(s):

A. AlQathama ◽

J. M. Prieto

Keyword(s):

Natural Products ◽

Cancer Treatment ◽

Therapeutic Potential ◽

Melanoma Cells ◽

Mechanisms Of Action ◽

Melanoma Metastasis ◽

Pharmacological Effects ◽

Cytotoxic Compounds

Natural products continue to provide lead cytotoxic compounds for cancer treatment but less attention has been given to antimigratory compounds. We here systematically and critically survey more than 30 natural products with direct in vitro and in vivo pharmacological effects on migration and/or metastasis of melanoma cells and chart the mechanisms of action for this underexploited property.

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Therapeutic potential of algal natural products against metabolic syndrome: A review of recent developments

Trends in Food Science & Technology ◽

10.1016/j.tifs.2020.01.020 ◽

2020 ◽

Vol 97 ◽

pp. 286-299 ◽

Cited By ~ 6

Author(s):

Ilekuttige Priyan Shanura Fernando ◽

BoMi Ryu ◽

Ginnae Ahn ◽

In-Kyu Yeo ◽

You-Jin Jeon

Keyword(s):

Metabolic Syndrome ◽

Natural Products ◽

Therapeutic Potential ◽

Recent Developments

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Natural Products as Source of Molecules with Therapeutic Potential

10.1007/978-3-030-00545-0 ◽

2018 ◽

Keyword(s):

Natural Products ◽

Therapeutic Potential

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Computer-Aided Drug Design (CADD) to De-Orphanize Marine Molecules: Finding Potential Therapeutic Agents for Neurodegenerative and Cardiovascular Diseases

Marine Drugs ◽

10.3390/md20010053 ◽

2022 ◽

Vol 20 (1) ◽

pp. 53

Author(s):

Laura Llorach-Pares ◽

Alfons Nonell-Canals ◽

Conxita Avila ◽

Melchor Sanchez-Martinez

Keyword(s):

Natural Products ◽

Drug Design ◽

Therapeutic Potential ◽

Marine Invertebrate ◽

In Silico Analysis ◽

New Drugs ◽

Computer Aided Drug Design ◽

Marine Habitats ◽

Computer Aided ◽

Promising Line

Computer-aided drug design (CADD) techniques allow the identification of compounds capable of modulating protein functions in pathogenesis-related pathways, which is a promising line on drug discovery. Marine natural products (MNPs) are considered a rich source of bioactive compounds, as the oceans are home to much of the planet’s biodiversity. Biodiversity is directly related to chemodiversity, which can inspire new drug discoveries. Therefore, natural products (NPs) in general, and MNPs in particular, have been used for decades as a source of inspiration for the design of new drugs. However, NPs present both opportunities and challenges. These difficulties can be technical, such as the need to dive or trawl to collect the organisms possessing the compounds, or biological, due to their particular marine habitats and the fact that they can be uncultivable in the laboratory. For all these difficulties, the contributions of CADD can play a very relevant role in simplifying their study, since, for example, no biological sample is needed to carry out an in-silico analysis. Therefore, the amount of natural product that needs to be used in the entire preclinical and clinical study is significantly reduced. Here, we exemplify how this combination between CADD and MNPs can help unlock their therapeutic potential. In this study, using a set of marine invertebrate molecules, we elucidate their possible molecular targets and associated therapeutic potential, establishing a pipeline that can be replicated in future studies.

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Neuroprotective Effects, Biological Activities and Therapeutic Potential of Phytochemicals: A Comprehensive Review

10.31487/j.ajmc.2020.01.04 ◽

2020 ◽

pp. 1-11

Author(s):

Xi-jun Wang ◽

Shi Qiu ◽

Aihua Zhang ◽

Jian-hua Miao ◽

Hui Sun ◽

...

Keyword(s):

Natural Products ◽

Neurological Disorders ◽

Chemical Biology ◽

Therapeutic Potential ◽

Biological Activities ◽

Therapeutic Agents ◽

Neuroprotective Effects ◽

Alternative Medicines ◽

Pharmacological Targets ◽

The World

The incidence of neurological disorders is growing in the world together with an increased lifespan. Nowadays, there are still no effective treatments for neurodegenerative pathology, which make necessary to search for new therapeutic agents. Natural products, most of them used in phytochemicals from herbal medicine, are considered promising alternatives for the treatment of neurodegenerative diseases. Numerous herbs have been applied to neurodegenerative disease treatments as complementary and alternative medicines. In the 21st century, omics-coupled functional pharmacology was developed for neurodegenerative drug discovery from natural products. In this article, we firstly provide the latest understanding of neurological disorders on risk factors, category, diagnosis and treatment, and then specially present an overview of natural products in neuroprotective effects research from chemical biology to pharmacological targets, and also discuss the natural products application and future challenge.

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Efficacy of natural formulations in bovine mastitis pathology: alternative solution to antibiotic treatment

Journal of Veterinary Research ◽

10.2478/jvetres-2020-0067 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Claudia Pașca ◽

Liviu Alexandru Mărghitaș ◽

Daniel Severus Dezmirean ◽

Ioana Adriana Matei ◽

Victorița Bonta ◽

...

Keyword(s):

Natural Products ◽

Therapeutic Potential ◽

Dairy Product ◽

Bovine Mastitis ◽

Antimicrobial Effect ◽

Economic Losses ◽

Standard Plate ◽

Conventional Antibiotics

AbstractIntroductionBovine mastitis is an inflammatory disease of the udder that causes important economic losses in the animal breeding and dairy product industries. Nowadays, the conventional livestock antibiotic treatments are slowly being replaced by alternative treatments. In this context, the main aim of this study was to evaluate the efficacy of natural products in alternative treatment of bovine mastitis.Material and MethodsTwo natural formulations with previously suggested in vitro antimicrobial effect were tested in vivo on mastitic cows. Animals with a positive diagnosis for mastitis (n = 20) were divided into three treatment groups: two groups (n = 8) were administered formulations of propolis, alcoholic extracts of Brewers Gold and Perle hops, plum lichen, common mallow, marigold, absinthe wormwood, black poplar buds, lemon balm, and essential oils of oregano, lavender, and rosemary designated R4 and R7 (differing only in the latter being more concentrated) and one group (n = 4) a conventional antibiotic mixture. In vivo efficacy of treatments was evaluated by somatic cell and standard plate counts, the treatment being considered efficacious when both parameters were under the maximum limit.ResultsR7 was effective in the most cases, being therapeutically bactericidal in six out of eight cows, while R4 gave good results in three out of eight cows, and conventional antibiotics cured one out of four.ConclusionThese results suggest the possible therapeutic potential of these natural products in bovine mastitis.

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