Ebselen and Analogues: Pharmacological Properties and Synthetic Strategies for Their Preparation

Ebselen is the leader of selenorganic compounds, and starting from its identification as mimetic of the key antioxidant enzyme glutathione peroxidase, several papers have appeared in literature claiming its biological activities. It was the subject of several clinical trials and it is currently in clinical evaluation for the treatment of COVID-19 patients. Given our interest in the synthesis and pharmacological evaluation of selenorganic derivatives with this review, we aimed to collect all the papers focused on the biological evaluation of ebselen and its close analogues, covering the timeline between 2016 and most of 2021. Our analysis evidences that, even if it lacks specificity when tested in vitro, being able to bind to every reactive cysteine, it proved to be always well tolerated in vivo, exerting no sign of toxicity whatever the administered doses. Besides, looking at the literature, we realized that no review article dealing with the synthetic approaches for the construction of the benzo[d][1,2]-selenazol-3(2H)-one scaffold is available; thus, a section of the present review article is completely devoted to this specific topic.

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Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190318120103 ◽

2019 ◽

Vol 20 (4) ◽

pp. 285-292 ◽

Cited By ~ 5

Author(s):

Abdullah M. Alnuqaydan ◽

Bilal Rah

Keyword(s):

Medicinal Plant ◽

Biological Activities ◽

Wide Spectrum ◽

Biological Properties ◽

In Vivo Model ◽

Drug Candidate ◽

Phytochemical Analysis ◽

Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

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Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules ◽

10.3390/molecules26092506 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2506

Author(s):

Wamidh H. Talib ◽

Ahmad Riyad Alsayed ◽

Alaa Abuawad ◽

Safa Daoud ◽

Asma Ismail Mahmod

Keyword(s):

Clinical Trials ◽

Current Knowledge ◽

Biological Activities ◽

Experimental Studies ◽

Therapeutic Effects ◽

Cell Proliferation Inhibition ◽

Different Types ◽

Solid Foundation

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

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Hemisynthesis and Biological Evaluation of Cinnamylated, Benzylated, and Prenylated Dihydrochalcones from a Common Bio-Sourced Precursor

Antibiotics ◽

10.3390/antibiotics10060620 ◽

2021 ◽

Vol 10 (6) ◽

pp. 620

Author(s):

Anne Ardaillou ◽

Jérôme Alsarraf ◽

Jean Legault ◽

François Simard ◽

André Pichette

Keyword(s):

Biological Activities ◽

Biological Evaluation ◽

Pharmacological Properties ◽

Cytotoxic Potential ◽

Naturally Occurring

Several families of naturally occurring C-alkylated dihydrochalcones display a broad range of biological activities, including antimicrobial and cytotoxic properties, depending on their alkylation sidechain. The catalytic Friedel–Crafts alkylation of the readily available aglycon moiety of neohesperidin dihydrochalcone was performed using cinnamyl, benzyl, and isoprenyl alcohols. This procedure provided a straightforward access to a series of derivatives that were structurally related to natural balsacones, uvaretin, and erioschalcones, respectively. The antibacterial and cytotoxic potential of these novel analogs was evaluated in vitro and highlighted some relations between the structure and the pharmacological properties of alkylated dihydrochalcones.

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Contribution to the biological interest of Valeriana officinalis: an update

Mediterranean Botany ◽

10.5209/mbot.70280 ◽

2021 ◽

Vol 42 ◽

pp. e67649

Author(s):

Marta Sánchez ◽

Elena González-Burgos ◽

Irene Iglesias ◽

M. Pilar Gómez-Serranillos Cuadrado

Keyword(s):

Clinical Trials ◽

Nervous System ◽

Biological Activities ◽

In Vivo Studies ◽

Neuroprotective Activity ◽

Future Research ◽

Valeriana Officinalis ◽

Valerenic Acid

Valeriana officinalis L. (Caprifoliaceae family) has been traditionally used to treat mild nervous tension and sleep problems. The basis of these activities are mainly attributed to valerenic acid through the modulation of the GABA receptor. Moreover, V. officinalis is claimed to have other biological activities such as cardiovascular benefits, anticancer, antimicrobial and spasmolytic. The current review aims to update the biological and pharmacological studies (in vitro, in vivo and clinical trials) of V. officinalis and its major secondary metabolites in order to guide future research. Databases PubMed, Science Direct and Scopus were used for literature search including original papers written in English and published between 2014 and 2020. There have been identified 33 articles which met inclusion criteria. Most of these works were performed with V. officinalis extracts and only a few papers (in vitro and in vivo studies) evaluated the activity of isolated compounds (valerenic acid and volvalerenal acid K). In vitro studies focused on studying antioxidant and neuroprotective activity. In vivo studies and clinical trials mainly investigated activities on the nervous system (anticonvulsant activity, antidepressant, cognitive problems, anxiety and sleep disorders). Just few studies were focused on other different activities, highlight effects on symptoms of premenstrual and postmenopausal syndromes. Valeriana officinalis continues to be one of the medicinal plants most used by today's society for its therapeutic properties and whose biological and pharmacological activities continue to arouse great scientific interest as evidenced in recent publications. This review shows scientific evidence on traditional uses of V. officinalis on nervous system.

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Hemoglobin F (HbF) inducers; History, Structure and Efficacies

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210521221615 ◽

2021 ◽

Vol 21 ◽

Author(s):

Zahra Hashemi ◽

Mohammad Ali Ebrahimzadeh

Keyword(s):

Clinical Trials ◽

Natural Products ◽

Biological Activities ◽

Globin Gene ◽

Beta Thalassemia ◽

Gene Promoters ◽

Hemoglobin F ◽

Chemical Structures

Abstract: Inherited beta-thalassemia is a major disease caused by irregular production of hemoglobin through reducing beta-globin chains. It has been observed that increasing fetal hemoglobin (HbF) production improves symptoms in the patients. Therefore, an increase in the level of HbF has been an operative approach for treating patients with beta-thalassemia. This review represents compounds with biological activities and pharmacological properties that can promote the HBF level and therefore used in the β-thalassemia patients' therapy. Various natural products with different mechanisms of action can be helpful in this medication cure. Clinical trials were efficient in improving the signs of patients. Association of in vivo, and in vitro studies of HbF induction and γ-globin mRNA growth displays that in vitro experiments could be an indicator of the in vivo response. The current study shows that; (a) HbF inducers can be grouped in several classes based on their chemical structures and mechanism of actions; b) According to several clinical trials, well-known drugs such as hydroxyurea and decitabine are useful HbF inducers; (c) The cellular biosensor K562 carrying genes under the control of the human γ-globin and β-globin gene promoters were applied during the researches; d) New natural products and lead compounds were found based on various studies as HbF inducers.

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Secondary Metabolites from Gorgonian Corals of the Genus Eunicella: Structural Characterizations, Biological Activities, and Synthetic Approaches

Molecules ◽

10.3390/molecules25010129 ◽

2019 ◽

Vol 25 (1) ◽

pp. 129

Author(s):

Dario Matulja ◽

Maria Kolympadi Markovic ◽

Gabriela Ambrožić ◽

Sylvain Laclef ◽

Sandra Kraljević Pavelić ◽

...

Keyword(s):

Secondary Metabolites ◽

Biological Activities ◽

Structural Characteristics ◽

Antimicrobial Activities ◽

Chemical Structures ◽

Gorgonian Corals ◽

Synthetic Approaches ◽

Further Development

Gorgonian corals, which belong to the genus Eunicella, are known as natural sources of diverse compounds with unique structural characteristics and interesting bioactivities both in vitro and in vivo. This review is focused primarily on the secondary metabolites isolated from various Eunicella species. The chemical structures of 64 compounds were divided into three main groups and comprehensively presented: a) terpenoids, b) sterols, and c) alkaloids and nucleosides. The observed biological activities of depicted metabolites with an impact on cytotoxic, anti-inflammatory, and antimicrobial activities were reviewed. The most promising biological activities of certain metabolites point to potential candidates for further development in pharmaceutical, cosmetic, and other industries, and are highlighted. Total synthesis or the synthetic approaches towards the desired skeletons or natural products are also summarized.

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Cafestol and Kahweol: A Review on Their Bioactivities and Pharmacological Properties

International Journal of Molecular Sciences ◽

10.3390/ijms20174238 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4238 ◽

Cited By ~ 15

Author(s):

Yaqi Ren ◽

Chunlan Wang ◽

Jiakun Xu ◽

Shuaiyu Wang

Keyword(s):

Furan Ring ◽

Biological Activities ◽

Pharmacological Properties ◽

Coffee Beans ◽

Anti Cancer ◽

Underlying Mechanisms ◽

Target Alternative ◽

Anti Inflammation

Cafestol and kahweol are natural diterpenes extracted from coffee beans. In addition to the effect of raising serum lipid, in vitro and in vivo experimental results have revealed that the two diterpenes demonstrate multiple potential pharmacological actions such as anti-inflammation, hepatoprotective, anti-cancer, anti-diabetic, and anti-osteoclastogenesis activities. The most relevant mechanisms involved are down-regulating inflammation mediators, increasing glutathione (GSH), inducing apoptosis of tumor cells and anti-angiogenesis. Cafestol and kahweol show similar biological activities but not exactly the same, which might due to the presence of one conjugated double bond on the furan ring of the latter. This review aims to summarize the pharmacological properties and the underlying mechanisms of cafestol-type diterpenoids, which show their potential as functional food and multi-target alternative medicine.

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Synthesis and Biological Evaluation of Polyfluoroalkylated Antipyrines and their Isomeric O-Methylpyrazoles

Medicinal Chemistry ◽

10.2174/1573406414666181106145435 ◽

2019 ◽

Vol 15 (5) ◽

pp. 521-536 ◽

Cited By ~ 6

Author(s):

Natalya Agafonova ◽

Evgeny Shchegolkov ◽

Yanina Burgart ◽

Victor Saloutin ◽

Alexandra Trefilova ◽

...

Keyword(s):

Biological Activities ◽

Biological Evaluation ◽

Antipyretic Activity ◽

Starting Point ◽

Anti Inflammatory ◽

Analgesic Activities ◽

Synthesis And Biological Evaluation ◽

Cox 1

Background: Formally belonging to the non-steroidal anti-inflammatory drug class pyrazolones have long been used in medical practices. Objective: Our goal is to synthesize N-methylated 1-aryl-3-polyfluoroalkylpyrazolones as fluorinated analogs of antipyrine, their isomeric O-methylated derivatives resembling celecoxib structure and evaluate biological activities of obtained compounds. Methods: In vitro (permeability) and in vivo (anti-inflammatory and analgesic activities, acute toxicity, hyperalgesia, antipyretic activity, “open field” test) experiments. To suggest the mechanism of biological activity, molecular docking of the synthesized compounds was carried out into the tyrosine site of COX-1/2. Conclusion: The trifluoromethyl antipyrine represents a valuable starting point in design of the lead series for discovery new antipyretic analgesics with anti-inflammatory properties.

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The phytochemistry and biological aspects of Caryocaraceae family

Revista Brasileira de Plantas Medicinais ◽

10.1590/s1516-05722013000200019 ◽

2013 ◽

Vol 15 (2) ◽

pp. 293-308 ◽

Cited By ~ 6

Author(s):

J. Ascari ◽

J.A. Takahashi ◽

M.A.D. Boaventura

Keyword(s):

Biological Activities ◽

Artemia Salina ◽

Biological Evaluation ◽

Phytochemical Study ◽

Medicinal Uses ◽

Isolation And Characterization ◽

Oil Source ◽

Phytochemical Studies

The Caryocaraceae family is constituted of 25 species distributed in two genera (Caryocar and Anthodiscus). Plants of this family have been used in several phytochemical studies for isolation and characterization of chemical compounds. Some of these studies evaluated in vitro and in vivo biological activities of extracts and pure substances isolated from plants of this family. Nine species of Anthodiscus genus have been described, while no phytochemical study related to them has been reported. On the other hand, Caryocar genus presents 16 species with several medicinal uses like for the treatment of colds and bronchitis, in the prevention of tumours, as a regulating agent of the menstrual flow, to treat ophthalmological problems and for the cure of hematomas and bruises. Some species of this genus were targeted by phytochemical studies and presented, in their composition, the following classes of secondary metabolites: triterpenes, fatty acids, tannins, carotenoids, triterpenic saponins, phenolic coumarins, phenolic glycosides, and others. The fruits of Caryocar species are very nutritive, containing in their composition fibers, proteins, carbohydrates and minerals. Seeds have been widely used as oil source with nutritional and cosmetic value. The biological evaluation of some species was carried out by using relevant biological assays such as: antioxidant, allelopathic and antifungal activities against Biomphalaria glabrata and toxicity on Artemia salina.

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Design, Synthesis and In-Vitro Biological Evaluation of Antofine and Tylophorine Prodrugs as Hypoxia-Targeted Anticancer Agents

Molecules ◽

10.3390/molecules26113327 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3327

Author(s):

Ziad Omran ◽

Chris P. Guise ◽

Linwei Chen ◽

Cyril Rauch ◽

Ashraf N. Abdalla ◽

...

Keyword(s):

Anticancer Agents ◽

Biological Activities ◽

Multidrug Resistant ◽

Biological Evaluation ◽

High Chemical ◽

Design Synthesis ◽

Hypoxic Conditions ◽

Cancerous Cell

Phenanthroindolizidines, such as antofine and tylophorine, are a family of natural alkaloids isolated from different species of Asclepiadaceas. They are characterized by interesting biological activities, such as pronounced cytotoxicity against different human cancerous cell lines, including multidrug-resistant examples. Nonetheless, these derivatives are associated with severe neurotoxicity and loss of in vivo activity due to the highly lipophilic nature of the alkaloids. Here, we describe the development of highly polar prodrugs of antofine and tylophorine as hypoxia-targeted prodrugs. The developed quaternary ammonium salts of phenanthroindolizidines showed high chemical and metabolic stability and are predicted to have no penetration through the blood–brain barrier. The designed prodrugs displayed decreased cytotoxicity when tested under normoxic conditions. However, their cytotoxic activity considerably increased when tested under hypoxic conditions.

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