Lichen-Derived Compounds and Extracts as Biologically Active Substances with Anticancer and Neuroprotective Properties

Lichens are a source of chemical compounds with valuable biological properties, structurally predisposed to penetration into the central nervous system (CNS). Hence, our research aimed to examine the biological potential of lipophilic extracts of Parmelia sulcata, Evernia prunastri, Cladonia uncialis, and their major secondary metabolites, in the context of searching for new therapies for CNS diseases, mainly glioblastoma multiforme (GBM). The extracts selected for the study were standardized for their content of salazinic acid, evernic acid, and (−)-usnic acid, respectively. The extracts and lichen metabolites were evaluated in terms of their anti-tumor activity, i.e. cytotoxicity against A-172 and T98G cell lines and anti-IDO1, IDO2, TDO activity, their anti-inflammatory properties exerted by anti-COX-2 and anti-hyaluronidase activity, antioxidant activity, and anti-acetylcholinesterase and anti-butyrylcholinesterase activity. The results of this study indicate that lichen-derived compounds and extracts exert significant cytotoxicity against GBM cells, inhibit the kynurenine pathway enzymes, and have anti-inflammatory properties and weak antioxidant and anti-cholinesterase properties. Moreover, evernic acid and (−)-usnic acid were shown to be able to cross the blood-brain barrier. These results demonstrate that lichen-derived extracts and compounds, especially (−)-usnic acid, can be regarded as prototypes of pharmacologically active compounds within the CNS, especially suitable for the treatment of GBM.

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The Molecular Diversity Scope of Urazole in the Synthesis of Organic Compounds

Current Organic Synthesis ◽

10.2174/1570179416666190925162215 ◽

2019 ◽

Vol 16 (7) ◽

pp. 953-967 ◽

Cited By ~ 1

Author(s):

Ghodsi M. Ziarani ◽

Fatemeh Mohajer ◽

Razieh Moradi ◽

Parisa Mofatehnia

Keyword(s):

Biological Activities ◽

Biological Properties ◽

Biologically Active ◽

Microtubule Assembly ◽

Heterocyclic Molecules ◽

Biological Perspective ◽

Highly Active ◽

Anti Inflammatory ◽

High Yields ◽

Short Time

Background: As a matter of fact, nitrogen as a hetero atom among other atoms has had an important role in active biological compounds. Since heterocyclic molecules with nitrogen are highly demanded due to biological properties, 4-phenylurazole as a compound containing nitrogen might be important in the multicomponent reaction used in agrochemicals, and pharmaceuticals. Considering the case of fused derivatives “pyrazolourazoles” which are highly applicable because of their application for analgesic, antibacterial, anti-inflammatory and antidiabetic activities as HSP-72 induction inhibitors (I and III) and novel microtubule assembly inhibitors. It should be mentioned that spiro-pyrazole also has biological activities like cytotoxic, antimicrobial, anticonvulsant, antifungal, anticancer, anti-inflammatory, and cardiotonic activities. Objective: Urazole has been used in many heterocyclic compounds which are valuable in organic syntheses. This review disclosed the advances in the use of urazole as the starting material in the synthesis of various biologically active molecules from 2006 to 2019. Conclusion: Compounds of urazole (1,2,4-triazolidine-3,5-dione) are the most important molecules which are highly active from the biological perspective in the pharmaceuticals as well as polymers. In summary, many protocols for preparations of the urazole derivatives from various substrates in multi-component reactions have been reported from different aromatic and aliphatic groups which have had carbonyl groups in their structures. It is noted that several catalysts have been synthesized to afford applicable molecules with urazole scaffolds. In some papers, being environmentally friendly, short time reactions and high yields are highlighted in the protocols. There is a room to synthesize new catalysts and perform new reactions by manipulating urazole to produce biologically active compounds, even producing chiral urazole component as many groups of chiral urazole compounds are important from biological perspective.

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Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review

Journal of Psychopharmacology ◽

10.1177/02698811211026426 ◽

2021 ◽

pp. 026988112110264

Author(s):

Emma Kopra ◽

Valeria Mondelli ◽

Carmine Pariante ◽

Naghmeh Nikkheslat

Keyword(s):

Systematic Review ◽

Animal Studies ◽

Bipolar Depression ◽

Strong Support ◽

Kynurenine Pathway ◽

Future Research ◽

Downstream Effects ◽

Tnf Α ◽

The Central Nervous System ◽

Anti Inflammatory

Background: Ketamine is a novel rapid-acting antidepressant with high efficacy in treatment-resistant patients. Its exact therapeutic mechanisms of action are unclear; however, in recent years its anti-inflammatory properties and subsequent downstream effects on tryptophan (TRP) metabolism have sparked research interest. Aim: This systematic review examined the effect of ketamine on inflammatory markers and TRP–kynurenine (KYN) pathway metabolites in patients with unipolar and bipolar depression and in animal models of depression. Methods: MEDLINE, Embase, and PsycINFO databases were searched on October 2020 (1806 to 2020). Results: Out of 807 initial results, nine human studies and 22 animal studies on rodents met the inclusion criteria. Rodent studies provided strong support for ketamine-induced decreases in pro-inflammatory cytokines, namely in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α and indicated anti-inflammatory effects on TRP metabolism, including decreases in the enzyme indoleamine 2,3-dioxygenase (IDO). Clinical evidence was less robust with high heterogeneity between sample characteristics, but most experiments demonstrated decreases in peripheral inflammation including in IL-1β, IL-6, and TNF-α. Preliminary support was also found for reduced activation of the neurotoxic arm of the KYN pathway. Conclusion: Ketamine appears to induce anti-inflammatory effects in at least a proportion of depressed patients. Suggestions for future research include investigation of markers in the central nervous system and examination of clinical relevance of inflammatory changes.

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Potential Anticancer Properties and Mechanisms of Action of Formononetin

BioMed Research International ◽

10.1155/2019/5854315 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Dongjun Jiang ◽

Azhar Rasul ◽

Rabia Batool ◽

Iqra Sarfraz ◽

Ghulam Hussain ◽

...

Keyword(s):

Trifolium Pratense ◽

Antioxidant Properties ◽

Cancer Therapeutics ◽

Biological Properties ◽

Anticancer Properties ◽

Biological Potential ◽

Pharmacological Potential ◽

Reported Data ◽

Pharmacologically Active ◽

Promising Source

Nature, a vast reservoir of pharmacologically active molecules, has been most promising source of drug leads for the cure of various pathological conditions. Formononetin is one of the bioactive isoflavones isolated from different plants mainly from Trifolium pratense, Glycine max, Sophora flavescens, Pycnanthus angolensis, and Astragalus membranaceus. Formononetin has been well-documented for its anti-inflammatory, anticancer, and antioxidant properties. Recently anticancer activity of formononetin is widely studied. This review aims to highlight the pharmacological potential of formononetin, thus providing an insight of its status in cancer therapeutics. Formononetin fights progression of cancer via inducing apoptosis, arresting cell cycle, and halting metastasis via targeting various pathways which are generally modulated in several cancers. Although reported data acclaims various biological properties of formononetin, further experimentation on mechanism of its action, medicinal chemistry studies, and preclinical investigations are surely needed to figure out full array of its pharmacological and biological potential.

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Anti-inflammatory effects of kinins via microglia in the central nervous system

Biological Chemistry ◽

10.1515/bc.2006.022 ◽

2006 ◽

Vol 387 (2) ◽

pp. 167-171 ◽

Cited By ~ 12

Author(s):

Mami Noda ◽

Helmut Kettenmann ◽

Keiji Wada

Keyword(s):

Biologically Active ◽

Prostaglandin E ◽

Active Peptides ◽

Tnf Α ◽

Biologically Active Peptides ◽

Murine Microglia ◽

Intracellular Ca ◽

The Central Nervous System ◽

Microglial Migration ◽

Anti Inflammatory

Abstract Kinins are important biologically active peptides that are up-regulated after lesions in both the peripheral and central (CNS) nervous systems. Microglia are immune cells in the CNS and play an important role in the defense of the neuronal parenchyma. In cultured murine microglia, bradykinin (BK) induces mobilization of intracellular Ca2+, microglial migration, and increases the release of nitric oxide and prostaglandin E2. On the other hand, BK attenuates lipopolysaccharide-activated TNF-α and IL-1β release. These results suggest that BK functions as a signal in brain trauma and may have an anti-inflammatory role in the CNS.

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Main Chain Polysulfoxides as Active ‘Stealth’ Polymers with Additional Antioxidant and Anti-Inflammatory Behaviour

International Journal of Molecular Sciences ◽

10.3390/ijms20184583 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4583 ◽

Cited By ~ 3

Author(s):

Farah El Mohtadi ◽

Richard d’Arcy ◽

Xiaoye Yang ◽

Zulfiye Yesim Turhan ◽

Aws Alshamsan ◽

...

Keyword(s):

Dermal Fibroblasts ◽

Biologically Active ◽

Anti Oxidant ◽

Anionic Ring ◽

Low Toxicity ◽

Anti Inflammatory ◽

Poly Ethylene ◽

Pharmacologically Active ◽

Poly Propylene

We present the evaluation of a sulfoxide-based polymer (poly(propylene sulfoxide), PPSO) as a potential ‘stealth’ macromolecule, and at the same time as a pharmacologically active (anti-inflammatory/anti-oxidant) material. The combination of these two concepts may at first seem peculiar since the gold standard polymer in biomaterials and drug delivery, poly(ethylene glycol) (PEG), is ‘stealth’ due to its chemical and biological inertness, which makes it hardly biologically active. Polysulfoxides, on the contrary, may couple a substantial inertness towards biomolecules under homeostatic conditions, with the possibility to scavenge reactive oxygen species (ROS) associated to inflammation. Polysulfoxides, therefore, are rather uniquely, ‘active’ ‘stealth’ polymers. Here, we describe the synthesis of PPSO through controlled oxidation of poly(propylene sulfide) (PPS), which on its turn was obtained via anionic ring-opening polymerization. In vitro, PPSO was characterized by a low toxicity (IC50 ~7 mg/mL at 24 h on human dermal fibroblasts) and a level of complement activation (in human plasma) and macrophage uptake slightly lower than PEG of a similar size. Importantly, and differently from PEG, on LPS-activated macrophages, PPSO showed a strong and dose-dependent ROS (hydrogen peroxide and hypochlorite)-scavenging activity, which resulted in a corresponding reduction of cytokine production.

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Influence of Incorporation of Different dn-Electron Metal Cations into Biologically Active System on Its Biological and Physicochemical Properties

International Journal of Molecular Sciences ◽

10.3390/ijms222312909 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12909

Author(s):

Bartłomiej Rogalewicz ◽

Małgorzata Szczesio ◽

Ewa Poleszak ◽

Joanna Kowalczyk ◽

Bernadeta Szewczyk ◽

...

Keyword(s):

Physicochemical Properties ◽

Magnetic Measurements ◽

Biological Properties ◽

Biologically Active ◽

X Ray Diffraction ◽

Active System ◽

X Ray ◽

The Central Nervous System ◽

New Compounds ◽

The Impact

Three new compounds, namely [HL]2+[CuCl4]2−, [HL]2+[ZnCl4]2−, and [HL]2+[CdCl4]2− (where L: imipramine) were synthesized and their physicochemical and biological properties were thoroughly investigated. All three compounds form isostructural, crystalline systems, which havea been studied using Single-Crystal X-ray diffraction analysis (SC-XRD) and Fourier-transform infrared spectroscopy (FTIR). The thermal stability was investigated using thermogravimetric analysis (TGA) and melting points for all compounds have been determined. Magnetic measurements were performed in order to study the magnetic properties of the compounds. The above mentioned techniques allowed us to comprehensively examine the physicochemical properties of the newly obtained compounds. The biological activity was investigated using the number of Zebrafish tests, as it is one of the most common models for studying the impact of newly synthesized compounds on the central nervous system (CNS), since this model is very similar to the human CNS.

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Synthesis and properties of S-derivatives of 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol

Current issues in pharmacy and medicine science and practice ◽

10.14739/2409-2932.2021.3.243176 ◽

2021 ◽

Vol 14 (3) ◽

pp. 268-274

Author(s):

S. O. Fedotov ◽

A. S. Hotsulia

Keyword(s):

In Silico ◽

Biological Properties ◽

Biologically Active ◽

Anticancer Activities ◽

Chemical Methods ◽

Biological Potential ◽

In Silico Studies ◽

Wide Range ◽

Physical And Chemical ◽

Derivatives Of

The combination of various heterocyclic systems with a wide range of properties is quite expedient and is, in practice, a justified direction for obtaining biologically active substances, which ultimately forms a favorable basis for the creation of drugs. In recent decades, the attention of scientists has been closely focused on nitrogen-containing heterocyclic compounds. Among such compounds, 1,2,4-triazole and pyrazole occupy a special place. Indeed, on the basis of these systems, a significant number of well-known drugs have been created, which are widely used at the present time. The aim of the work was the synthesis of S-derivatives of 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol, study of their physical and chemical properties, pre-screening studies with subsequent establishment of the feasibility of further pharmacological studies. Materials and methods. Experimental methods of organic chemistry: synthesis using microwave activation, physical and chemical methods for the analysis of organic compounds (determination of the melting point, elemental analysis, 1H NMR, IR spectroscopy and chromatography-mass spectrometry). Methods for in silico pre-screening studies to establish the biological potential in several synthesized compounds (molecular docking). Results. 10 new S-derivatives of 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol were synthesized. The structure of the obtained compounds was confirmed by a set of physical and chemical methods of analysis. According to the results of prescreening studies, the main directions of research of biological properties of synthesized compounds were provided. Conclusions. The expediency of using microwave irradiation in the synthesis of a series of S-alkyl derivatives of 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol had been proved. Based on the results of in silico studies, the expediency of further studies of anti-inflammatory, antifungal and anticancer activities in several synthesized compounds had been substantiated.

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Recent Advances in the Use of the Dimerization Strategy as a Means to Increase the Biological Potential of Natural or Synthetic Molecules

Molecules ◽

10.3390/molecules26082340 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2340

Author(s):

Alexis Paquin ◽

Carlos Reyes-Moreno ◽

Gervais Bérubé

Keyword(s):

Anticancer Agents ◽

Scientific Community ◽

Antibacterial Agents ◽

Biological Properties ◽

Biologically Active ◽

Special Focus ◽

Reaction Sequence ◽

Polyphenol Compounds ◽

Recent Advances ◽

Biological Potential

The design of C2-symmetric biologically active molecules is a subject of interest to the scientific community. It provides the possibility of discovering medicine with higher biological potential than the parent drugs. Such molecules are generally produced by classic chemistry, considering the shortness of reaction sequence and the efficacy for each step. This review describes and analyzes recent advances in the field and emphasizes selected C2-symmetric molecules (or axial symmetric molecules) made during the last 10 years. However, the description of the dimers is contextualized by prior work allowing its development, and they are categorized by their structure and/or by their properties. Hence, this review presents dimers composed of steroids, sugars, and nucleosides; known and synthetic anticancer agents; polyphenol compounds; terpenes, known and synthetic antibacterial agents; and natural products. A special focus on the anticancer potential of the dimers transpires throughout the review, notwithstanding their structure and/or primary biological properties.

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In vitro and in vivo biological activities of azulene derivatives with potential applications in medicine

Medicinal Chemistry Research ◽

10.1007/s00044-021-02701-0 ◽

2021 ◽

Author(s):

Paweł Bakun ◽

Beata Czarczynska-Goslinska ◽

Tomasz Goslinski ◽

Sebastian Lijewski

Keyword(s):

Biological Activities ◽

Biological Properties ◽

Biologically Active ◽

Peptic Ulcers ◽

Artemisia Absinthium ◽

Potential Applications ◽

Anti Inflammatory ◽

Unique Chemical

AbstractAzulene is an aromatic hydrocarbon that possesses a unique chemical structure and interesting biological properties. Azulene derivatives, including guaiazulene or chamazulene, occur in nature as components of many plants and mushrooms, such as Matricaria chamomilla, Artemisia absinthium, Achillea millefolium, and Lactarius indigo. Due to physicochemical properties, azulene and its derivatives have found many potential applications in technology, especially in optoelectronic devices. In medicine, the ingredients of these plants have been widely used for hundreds of years in antiallergic, antibacterial, and anti-inflammatory therapies. Herein, the applications of azulene, its derivatives and their conjugates with biologically active compounds are presented. The potential use of these compounds concerns various areas of medicine, including anti-inflammatory with peptic ulcers, antineoplastic with leukemia, antidiabetes, antiretroviral with HIV-1, antimicrobial, including antimicrobial photodynamic therapy, and antifungal.

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Linalool – a Review of a Biologically Active Compound of Commercial Importance

Natural Product Communications ◽

10.1177/1934578x0800300727 ◽

2008 ◽

Vol 3 (7) ◽

pp. 1934578X0800300 ◽

Cited By ~ 9

Author(s):

Guy P. P. Kamatou ◽

Alvaro M. Viljoen

Keyword(s):

Essential Oils ◽

Biological Activities ◽

Modern Society ◽

Biological Properties ◽

Biologically Active ◽

In Vivo Studies ◽

The Central Nervous System ◽

Anti Oxidant ◽

Domestic Products

Since the earliest times fragrant materials have been used in rituals. Today, a lucrative industry has developed to produce and deliver fragrances and aromatic chemicals with various applications in modern society. Linalool, a much sought after compound in the flavor and fragrance industry is a monoterpene alcohol which occurs naturally in many aromatic plants. Linalool and linalool-rich essential oils are known to exhibit various biological activities such as antimicrobial, anti-inflammatory, anticancer, anti-oxidant properties and several in vivo studies have confirmed various effects of linalool on the central nervous system. The applications of linalool are not confined to simply adding or enhancing a specific scent to domestic products such as soaps, detergents and shampoos. Linalool also plays an import role in nature as a key compound in the complex pollination biology of various plant species to ensure reproduction and survival. Linalool is also a key compound for the industrial production of a variety of fragrance chemicals such as geraniol, nerol, citral and its derivatives, as well as a lead compound in the synthesis of vitamins A and E. The repellent properties of linalool on various crop-destroying insects has been well documented accentuating the application of this molecule in eco-friendly pest management. This review aims to highlight the various biological properties of linalool and to emphasize the value of linalool and linalool-rich essential oils in phytotherapy.

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