A chemophenetic study of the genus Maytenus s.l. (Celastraceae): contribution to the rational search of its bioactive metabolites

Abstract Maytenus s.l. is a genus of the Celastraceae family and many of its species are used in traditional medicine. Most of the substances responsible for the biological activities of plants come from their secondary metabolism, such as terpenoids and flavonoids, which have multiple functions in the plant and can occur in a similar way in plant groups. Chemophenetics analyzes the occurrence of these substances in a taxon and can infer evolutionary trends and contribute to the rational search for new drugs. Chemosystematic parameters were used to analyze the data obtained through a bibliographic survey. The species of Maytenus s.l. were separated into three groups: species with accepted names, synonymous species with the genus Monteverdia and synonymous species with the genus Gymnosporia. Due to their great occurrence and structural variety in Maytenus s.l., triterpenes were chosen as chemosystematic markers, with friedelanes and quinone methide triterpenes being the most expressive types. Studies have already demonstrated the analgesic potential of quinone methides and the antitumor potential of phenolic triterpenes and dimers of these units. Together, the three classes assist in the circumscription of Maytenus s.s. and Monteverdia, while lupanes can be used in the separation of these genera. Oleanans are representative of Gymnosporia.

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BIOLOGICAL ACTIVITIES OF ALTERNARIA SP. RL4 – A POTENT ENDOPHYTIC FUNGUS ASSOCIATED WITH RAUVOLFIA SERPENTINA L. BENTH.

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i11.27500 ◽

2018 ◽

Vol 11 (11) ◽

pp. 178

Author(s):

Ranjan Ghosh ◽

Soma Barman ◽

Pavan Kumar Jgs ◽

Narayan C Mandal

Keyword(s):

Mode Of Action ◽

Pathogenic Bacteria ◽

Biological Activities ◽

Fungal Endophytes ◽

Radical Scavenging ◽

New Drugs ◽

Bioactive Metabolites ◽

Gram Positive ◽

Rauvolfia Serpentina ◽

Alternaria Sp

Objectives: Endophytic fungi are considered as an important source of bioactive metabolites. The present study focused on the isolation of potent endophytic fungal strains from well-known medicinal plant Rauvolfia serpentina L. Benth. having biological activities.Materials & Methods: Fungal endophytes were isolated from aerial parts of the plant and the potent strain was selected on the basis of antibacterial activities of cell-free supernatant (CFS). Ethyl acetate (EA) extraction of CFS was done and mode of action of EA fraction was checked against pathogenic bacteria. EA fraction was also analyzed by thin-layer chromatography (TLC). In addition, antioxidant activity was checked by 1,1-Diphenyl- 2-picrylhydrazyl-free radical scavenging assay and anticancer activity was checked against breast cancer cell line MCF-7 by MTT assay.Results: Among the different endophytic fungal isolates, CFS of Alternaria sp. RL4 produced prominent zones of inhibition against numbers of Gram-positive pathogenic bacteria including Staphylococcus aureus (12±0.5 mm) and Listeria monocytogenes (17±2.0 mm). Massive reductions in bacterial CFS were noticed upon treatment with EA fraction (2 mg/ml). It also showed strong cidal mode of action against Gram-positive organisms. TLC analysis revealed the production of two different compounds with antibacterial potentials. In addition, EA fraction of RL4 showed very good antioxidant property with an IC50 value of 49.80±2.11μg/ml. MTT assay also suggested the anticancerous properties of EA fraction of RL4.Conclusion: Alternaria sp. RL4 could be a very good source of bioactive compounds for the development of new drugs.

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New Drugs from the Sea: Pro-Apoptotic Activity of Sponges and Algae Derived Compounds

Marine Drugs ◽

10.3390/md17010031 ◽

2019 ◽

Vol 17 (1) ◽

pp. 31 ◽

Cited By ~ 19

Author(s):

Giuseppe Ercolano ◽

Paola De Cicco ◽

Angela Ianaro

Keyword(s):

Molecular Mechanisms ◽

Human Cancer ◽

Biological Activities ◽

Mitochondrial Pathway ◽

Marine Organisms ◽

New Drugs ◽

Bioactive Molecules ◽

Bioactive Metabolites ◽

Apoptotic Activity

Natural compounds derived from marine organisms exhibit a wide variety of biological activities. Over the last decades, a great interest has been focused on the anti-tumour role of sponges and algae that constitute the major source of these bioactive metabolites. A substantial number of chemically different structures from different species have demonstrated inhibition of tumour growth and progression by inducing apoptosis in several types of human cancer. The molecular mechanisms by which marine natural products activate apoptosis mainly include (1) a dysregulation of the mitochondrial pathway; (2) the activation of caspases; and/or (3) increase of death signals through transmembrane death receptors. This great variety of mechanisms of action may help to overcome the multitude of resistances exhibited by different tumour specimens. Therefore, products from marine organisms and their synthetic derivates might represent promising sources for new anticancer drugs, both as single agents or as co-adjuvants with other chemotherapeutics. This review will focus on some selected bioactive molecules from sponges and algae with pro-apoptotic potential in tumour cells.

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Bioactive Metabolites from Pathogenic and Endophytic Fungi of Forest Trees

Current Medicinal Chemistry ◽

10.2174/0929867324666170314145159 ◽

2018 ◽

Vol 25 (2) ◽

pp. 208-252 ◽

Cited By ~ 26

Author(s):

Marco Masi ◽

Lucia Maddau ◽

Benedetto Teodoro Linaldeddu ◽

Bruno Scanu ◽

Antonio Evidente ◽

...

Keyword(s):

Secondary Metabolites ◽

Endophytic Fungi ◽

Biological Activities ◽

Terrestrial Ecosystems ◽

Biological Properties ◽

Research Literature ◽

New Drugs ◽

Bioactive Metabolites ◽

Bibliographic Databases ◽

Forest Trees

Background: Fungi play an important role in terrestrial ecosystems interacting positively or negatively with plants. These interactions are complex and the outcomes are different depending on the fungal lifestyles, saprotrophic, mutualistic or pathogenic. Furthermore, fungi are well known for producing secondary metabolites, originating from different biosynthetic pathways, which possess biological properties of considerable biotechnological interest. Among the terrestrial ecosystems, temperate forests represent an enormous reservoir of fungal diversity. This review will highlight the goldmine of secondary metabolites produced by pathogenic and endophytic fungi of forest trees with focus on their biological activities. Methods: A structured search of bibliographic databases for peer-reviewed research literature was undertaken using a research discovery application providing access to a large and authoritative source of references. The papers selected were examined and the main results were reported and discussed. Results: Two hundred forthy-one papers were included in the review, outlined a large number of secondary metabolites produced by pathogenic and endophiltic fungi and their biological activities, including phytotoxic, antifungal, antioomycetes, antibacterial, brine shrimp lethality, mosquito biting deterrence and larvicidal, cytotoxic, antiproliferative and many other bioactivities. Conclusion: The findings of this review confirm the importance of secondary metabolites produced by pathogenic and endophytic fungi from forest plants growing in temperate regions as an excellent prospects to discover compounds with new bioactivities and mode of actions. In addition, the potential of some metabolites as a source of new drugs and biopesticides is underlined.

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Metabolomics of Healthy Berry Fruits

Current Medicinal Chemistry ◽

10.2174/0929867323666161206100006 ◽

2019 ◽

Vol 25 (37) ◽

pp. 4888-4902 ◽

Cited By ~ 3

Author(s):

Gilda D'Urso ◽

Sonia Piacente ◽

Cosimo Pizza ◽

Paola Montoro

Keyword(s):

Biological Activities ◽

Biologically Active ◽

In Vivo Studies ◽

Bioactive Metabolites ◽

Active Metabolites ◽

Positive Effects ◽

Cell Functions ◽

Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

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Synthesis and Biological Activity of Hydrazones and Derivatives: A Review

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666191014142448 ◽

2020 ◽

Vol 20 (5) ◽

pp. 342-368 ◽

Cited By ~ 5

Author(s):

Juliana de Oliveira Carneiro Brum ◽

Tanos Celmar Costa França ◽

Steven R. LaPlante ◽

José Daniel Figueroa Villar

Keyword(s):

Biological Activity ◽

Medicinal Chemistry ◽

Biological Activities ◽

New Drugs ◽

New Drug ◽

Cancer Inflammation

Hydrazones and their derivatives are very important compounds in medicinal chemistry due to their reported biological activity for the treatment of several diseases, like Alzheimer’s, cancer, inflammation, and leishmaniasis. However, most of the investigations on hydrazones available in literature today are directed to the synthesis of these molecules with little discussion available on their biological activities. With the purpose of bringing lights into this issue, we performed a revision of the literature and wrote this review based on some of the most current research reports of hydrazones and derivatives, making it clear that the synthesis of these molecules can lead to new drug prototypes. Our goal is to encourage more studies focused on the synthesis and evaluation of new hydrazones, as a contribution to the development of potential new drugs for the treatment of various diseases.

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Recent progress in marine mollusks from the South China Sea: chemical and ecological studies

Mini-Reviews in Organic Chemistry ◽

10.2174/1570178617999200629154749 ◽

2020 ◽

Vol 17 ◽

Author(s):

Song-Wei Li ◽

Yue-Wei Guo

Keyword(s):

South China Sea ◽

South China ◽

Biological Activities ◽

The South China Sea ◽

Bioactive Metabolites ◽

Research Subject ◽

Ecological Studies ◽

The South ◽

China Sea ◽

Marine Mollusks

: Marine mollusks are a prolific source of secondary metabolites with complex/diverse structures and various aspects of biological activities. For above mentioned reason, these animals have been being extensively explored and became the hotspot of research subject in the recent years. It is well documented that mollusks can escape from predation by utilizing bioactive metabolites as defensive chemicals. In the last decade, the possible diet relationship between the South China Sea mollusks and their related potential prey organisms, including sponges, corals, algae, etc. have been systematically investigated. A series of interesting results have been obtained concerning the chemistry, chemoecology and pharmacological profiles of the studied marine organisms. The present review focuses on recent development dealing with chemistry, chemoecology, and bioactivity of the South China Sea mollusks and their dietary organisms.

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Advances in Triazole Synthesis from Copper-catalyzed Azide-alkyne Cycloadditions (CuAAC) Based on Eco-friendly Procedures

Current Organic Synthesis ◽

10.2174/1570179416666190104141454 ◽

2019 ◽

Vol 16 (2) ◽

pp. 244-257 ◽

Cited By ~ 2

Author(s):

Marcus Vinicius Nora de Souza ◽

Cristiane França da Costa ◽

Victor Facchinetti ◽

Claudia Regina Brandão Gomes ◽

Paula Mázala Pacheco

Keyword(s):

Biological Activities ◽

Reaction Times ◽

Water Extract ◽

Fish Bone ◽

New Drugs ◽

Bone Powder ◽

Wide Range ◽

Recoverable Catalysts ◽

Egg Shell ◽

Work Up

Background: 1,2,3-triazoles are an important class of organic compounds and because of their aromatic stability, they are not easily reduced, oxidized or hydrolyzed in acidic and basic environments. Moreover, 1,2,3-triazole derivatives are known by their important biological activities and have drawn considerable attention due to their variety of properties. The synthesis of this nucleus, based on the click chemistry concept, through the 1,3-dipolar addition reaction between azides and alkynes is a well-known procedure. This reaction has a wide range of applications, especially on the development of new drugs. Methods: The most prominent eco-friendly methods for the synthesis of triazoles under microwave irradiation published in articles from 2012-2018 were reviewed. Results: In this review, we cover some of the recent eco-friendly CuAAC procedures for the click synthesis of 1,2,3-triazoles with remarks to new and easily recoverable catalysts, such as rhizobial cyclic β-1,2 glucan; WEB (water extract of banana); biosourced cyclosophoraose (CyS); egg shell powder (ESP); cyclodextrin (β- CD); fish bone powder; nanoparticle-based catalyst, among others. Conclusion: These eco-friendly procedures are a useful tool for the synthesis of 1,2,3-triazoles, providing many advantages on the synthesis of this class, such as shorter reaction times, easier work-up and higher yields when compared to classical procedures. Moreover, these methodologies can be applied to the industrial synthesis of drugs and to other areas.

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Plant-Derived Nano and Microvesicles for Human Health and Therapeutic Potential in Nanomedicine

Pharmaceutics ◽

10.3390/pharmaceutics13040498 ◽

2021 ◽

Vol 13 (4) ◽

pp. 498

Author(s):

Mariaevelina Alfieri ◽

Antonietta Leone ◽

Alfredo Ambrosone

Keyword(s):

Therapeutic Potential ◽

Biological Activities ◽

Plant Biotechnology ◽

Bioactive Metabolites ◽

Anticancer Activities ◽

Long Distance ◽

In Vivo Models ◽

Therapeutic Tools

Plants produce different types of nano and micro-sized vesicles. Observed for the first time in the 60s, plant nano and microvesicles (PDVs) and their biological role have been inexplicably under investigated for a long time. Proteomic and metabolomic approaches revealed that PDVs carry numerous proteins with antifungal and antimicrobial activity, as well as bioactive metabolites with high pharmaceutical interest. PDVs have also been shown to be also involved in the intercellular transfer of small non-coding RNAs such as microRNAs, suggesting fascinating mechanisms of long-distance gene regulation and horizontal transfer of regulatory RNAs and inter-kingdom communications. High loading capacity, intrinsic biological activities, biocompatibility, and easy permeabilization in cell compartments make plant-derived vesicles excellent natural or bioengineered nanotools for biomedical applications. Growing evidence indicates that PDVs may exert anti-inflammatory, anti-oxidant, and anticancer activities in different in vitro and in vivo models. In addition, clinical trials are currently in progress to test the effectiveness of plant EVs in reducing insulin resistance and in preventing side effects of chemotherapy treatments. In this review, we concisely introduce PDVs, discuss shortly their most important biological and physiological roles in plants and provide clues on the use and the bioengineering of plant nano and microvesicles to develop innovative therapeutic tools in nanomedicine, able to encompass the current drawbacks in the delivery systems in nutraceutical and pharmaceutical technology. Finally, we predict that the advent of intense research efforts on PDVs may disclose new frontiers in plant biotechnology applied to nanomedicine.

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Nanoformulations for Delivery of Pentacyclic Triterpenoids in Anticancer Therapies

Molecules ◽

10.3390/molecules26061764 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1764

Author(s):

Anna Kaps ◽

Paweł Gwiazdoń ◽

Ewa Chodurek

Keyword(s):

Water Solubility ◽

Biological Activities ◽

Premature Mortality ◽

Delivery Systems ◽

Pentacyclic Triterpenoids ◽

Anticancer Properties ◽

Oncological Patients ◽

Antitumor Potential ◽

Ring Structures

The search for safe and effective anticancer therapies is one of the major challenges of the 21st century. The ineffective treatment of cancers, classified as civilization diseases, contributes to a decreased quality of life, health loss, and premature mortality in oncological patients. Many natural phytochemicals have anticancer potential. Pentacyclic triterpenoids, characterized by six- and five-membered ring structures, are one of the largest class of natural metabolites sourced from the plant kingdom. Among the known natural triterpenoids, we can distinguish lupane-, oleanane-, and ursane-types. Pentacyclic triterpenoids are known to have many biological activities, e.g., anti-inflammatory, antibacterial, hepatoprotective, immunomodulatory, antioxidant, and anticancer properties. Unfortunately, they are also characterized by poor water solubility and, hence, low bioavailability. These pharmacological properties may be improved by both introducing some modifications to their native structures and developing novel delivery systems based on the latest nanotechnological achievements. The development of nanocarrier-delivery systems is aimed at increasing the transport capacity of bioactive compounds by enhancing their solubility, bioavailability, stability in vivo and ensuring tumor-targeting while their toxicity and risk of side effects are significantly reduced. Nanocarriers may vary in sizes, constituents, shapes, and surface properties, all of which affect the ultimate efficacy and safety of a given anticancer therapy, as presented in this review. The presented results demonstrate the high antitumor potential of systems for delivery of pentacyclic triterpenoids.

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GraphBind: protein structural context embedded rules learned by hierarchical graph neural networks for recognizing nucleic-acid-binding residues

Nucleic Acids Research ◽

10.1093/nar/gkab044 ◽

2021 ◽

Author(s):

Ying Xia ◽

Chun-Qiu Xia ◽

Xiaoyong Pan ◽

Hong-Bin Shen

Keyword(s):

Neural Networks ◽

Nucleic Acid ◽

Biological Activities ◽

New Drugs ◽

Superior Performance ◽

Nucleic Acid Binding ◽

Hierarchical Graph ◽

Binding Residue ◽

Binding Residues ◽

Graph Neural Networks

Abstract Knowledge of the interactions between proteins and nucleic acids is the basis of understanding various biological activities and designing new drugs. How to accurately identify the nucleic-acid-binding residues remains a challenging task. In this paper, we propose an accurate predictor, GraphBind, for identifying nucleic-acid-binding residues on proteins based on an end-to-end graph neural network. Considering that binding sites often behave in highly conservative patterns on local tertiary structures, we first construct graphs based on the structural contexts of target residues and their spatial neighborhood. Then, hierarchical graph neural networks (HGNNs) are used to embed the latent local patterns of structural and bio-physicochemical characteristics for binding residue recognition. We comprehensively evaluate GraphBind on DNA/RNA benchmark datasets. The results demonstrate the superior performance of GraphBind than state-of-the-art methods. Moreover, GraphBind is extended to other ligand-binding residue prediction to verify its generalization capability. Web server of GraphBind is freely available at http://www.csbio.sjtu.edu.cn/bioinf/GraphBind/.

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