Chronic Behavioral and Neurochemical Effects of Four Novel -Benzyl-2-phenylethylamine Derivatives Recently Identified as "Psychoactive" in Adult Zebrafish Screens.

Potently affecting human and animal brain and behavior, hallucinogenic drugs have recently emerged as potentially promising agents in psychopharmacotherapy. Complementing laboratory rodents, the zebrafish () is a powerful model organism for screening neuroactive drugs, including hallucinogens. Here, we tested four novel -benzyl-2-phenylethylamine (NBPEA) derivatives with 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the -F, -Cl, and -OCF substitutions in the position of the phenyl ring of the -benzyl moiety (34H-NBF, 34H-NBCl, 24H-NBOMe(F), and 34H-NBOMe(F)), assessing their behavioral and neurochemical effects following chronic 14 day treatment in adult zebrafish.

Antitumor Profile of Carbon-Bridged Steroids (CBS) and Triterpenoids.

This review focuses on the rare group of carbon-bridged steroids (CBS) and triterpenoids found in various natural sources such as green, yellow-green, and red algae, marine sponges, soft corals, ascidians, starfish, and other marine invertebrates. In addition, this group of rare lipids is found in amoebas, fungi, fungal endophytes, and plants. For convenience, the presented CBS and triterpenoids are divided into four groups, which include: (a) CBS and triterpenoids containing a cyclopropane group; (b) CBS and triterpenoids with cyclopropane ring in the side chain; (c) CBS and triterpenoids containing a cyclobutane group; (d) CBS and triterpenoids containing cyclopentane, cyclohexane or cycloheptane moieties.

Sulfated and Sulfur-Containing Steroids and Their Pharmacological Profile.

The review focuses on sulfated steroids that have been isolated from seaweeds, marine sponges, soft corals, ascidians, starfish, and other marine invertebrates. Sulfur-containing steroids and triterpenoids are sourced from sedentary marine coelenterates, plants, marine sediments, crude oil, and other geological deposits. The review presents the pharmacological profile of sulfated steroids, sulfur-containing steroids, and triterpenoids, which is based on data obtained using the PASS program.

Antiprotozoal and Antitumor Activity of Natural Polycyclic Endoperoxides: Origin, Structures and Biological Activity.

Polycyclic endoperoxides are rare natural metabolites found and isolated in plants, fungi, and marine invertebrates. The purpose of this review is a comparative analysis of the pharmacological potential of these natural products. According to PASS (Prediction of Activity Spectra for Substances) estimates, they are more likely to exhibit antiprotozoal and antitumor properties.

Chemical Diversity of Soft Coral Steroids and Their Pharmacological Activities.

The review is devoted to the chemical diversity of steroids produced by soft corals and their determined and potential activities. There are about 200 steroids that belong to different types of steroids such as secosteroids, spirosteroids, epoxy- and peroxy-steroids, steroid glycosides, halogenated steroids, polyoxygenated steroids and steroids containing sulfur or nitrogen heteroatoms. Of greatest interest is the pharmacological activity of these steroids.

Pharmacological profile of natural and synthetic compounds with rigid adamantane-based scaffolds as potential agents for the treatment of neurodegenerative diseases.

This review is dedicated to the comparative analysis of structure-activity relationships for more than 75 natural and synthetic derivatives of adamantane. Some of these compounds, such as amantadine and memantine, are currently used to treat dementia, Alzheimer's and Parkinson's diseases and other neurodegenerative diseases. The data presented show that the pharmacological potential of 1-fluoro- and 1-phosphonic acid adamantane derivatives against Alzheimer's and Parkinson's diseases and other neurodegenerative diseases exceeds those of well-known amantadine and memantine.

Natural and synthetic drugs used for the treatment of the dementia.

This review is devoted to comparative pharmacological analysis of synthetic drugs such as memantine and its isomers, as well as tacrine, velnacrine, rivastigmine, and donepezil, with natural alkaloids, terpenoids, and triterpenoid peroxides, which are used to treat dementia, Alzheimer's and Parkinson's diseases, myasthenia gravis and other neurodegenerative diseases. Recently discovered by French scientists from Marseille triterpenoid hydroperoxides demonstrate high activity as potential therapeutic agents for the treatment of dementia. The information presented in this review is of great interest to pharmacologists, medical chemists, physiologists, neurologists and doctors, as well as for the pharmaceutical industry.

Combined network pharmacology and virtual reverse pharmacology approaches for identification of potential targets to treat vascular dementia.

Dementia is a major cause of disability and dependency among older people. If the lives of people with dementia are to be improved, research and its translation into druggable target are crucial. Ancient systems of healthcare (Ayurveda, Siddha, Unani and Sowa-Rigpa) have been used from centuries for the treatment vascular diseases and dementia.

Hydroperoxy steroids and triterpenoids derived from plant and fungi: Origin, structures and biological activities.

Hydroperoxides (R-OOH) represent a small family of natural metabolites that have been isolated from higher plants, fungi, and marine organisms. This paper is devoted to the distribution of hydroperoxides in plants, fungi and terrestrial fungal endophytes and their biological activity. Hydroperoxides of plants demonstrate a wide range of biological activities however, antineoplastic and anti-ulcerative are most characteristic with confidence from 91 to 98 percent.

Naturally occurring of α,β-diepoxy-containing compounds: origin, structures, and biological activities.

Diepoxy-containing compounds are widely distributed in nature. These metabolites are found in plants and marine organisms and are also produced by many microorganisms, fungi, or fungal endophytes. Many of these metabolites are antibiotics and exhibit a wide variety of biological activities.

Hydroperoxides derived from marine sources: origin and biological activities.

Hydroperoxides are a small and interesting group of biologically active natural marine compounds. All these metabolites contain a group (R-O-O-H). In this mini-review, studies of more than 80 hydroperoxides isolated from bacteria, fungi, algae, and marine invertebrates are described.

Oxetane-containing metabolites: origin, structures, and biological activities.

Cyclobutanes containing one oxygen atom in a molecule are called oxetane-containing compounds (OCC). More than 600 different OCC are found in nature; they are produced by microorganisms, and also found in marine invertebrates and algae. The greatest number of them is found in plants belonging to the genus Taxus.

Highly oxygenated isoprenoid lipids derived from fungi and fungal endophytes: Origin and biological activities.

This mini review is devoted to highly oxygenated isoprenoid lipids (HOIL) that are produced by fungi and fungal endophytes from various ecological niches, both terrestrial and aquatic. Steroids were distributed as from edible cultivated fungi, as well as fungi collected in forests. Fungal endophytes were generally isolated from plants and cultured to obtain sufficient biomass.

Steroid phosphate esters and phosphonosteroids and their biological activities.

Steroid phosphate esters are very rare natural lipids that have been comparatively recently isolated from fractions of polar lipids of marine sponges and starfish. These steroids exhibit interesting biological activities. When using the PASS computer program, we showed that many of steroid phosphate esters showed antifungal, antihypercholesterolemic, anesthetic, and other activities with a confidence of 73 to 93%.

Peroxy steroids derived from plant and fungi and their biological activities.

Peroxides represent a large and interesting group of biologically active natural compounds. All these metabolites contain a peroxide group (R-O-O-R). This review describes studies of more than 60 peroxides isolated from plants and fungi.

Naturally occurring aromatic steroids and their biological activities.

The present review describes the distribution and biological activities of natural mono-, di-, and triaromatic steroids. It is shown that the producers of aromatic steroids are microorganisms, fungi, and marine invertebrates, and also they were found in plants, animals, marine sediments, and karst deposits. Eighty biologically active aromatic steroids likely have an anti-tumor, anti-inflammatory, and neuroprotection activity with a confidence of 78 to 92%.

CLC-Pred: A freely available web-service for in silico prediction of human cell line cytotoxicity for drug-like compounds.

In silico methods of phenotypic screening are necessary to reduce the time and cost of the experimental in vivo screening of anticancer agents through dozens of millions of natural and synthetic chemical compounds. We used the previously developed PASS (Prediction of Activity Spectra for Substances) algorithm to create and validate the classification SAR models for predicting the cytotoxicity of chemicals against different types of human cell lines using ChEMBL experimental data. A training set from 59,882 structures of compounds was created based on the experimental data (IG50, IC50, and % inhibition values) from ChEMBL.

Pharmacological and Predicted Activities of Natural Azo Compounds.

This paper describes research on natural azo compounds isolated from fungi, plant, bacteria, and invertebrates. More than 120 biologically active diazene containing alkaloids demonstrate confirmed pharmacological activity, including antitumor, antimicrobial, and antibacterial effects. The structures, origin, and biological activities of azo compounds are reviewed.

Naturally occurring plant isoquinoline N-oxide alkaloids: their pharmacological and SAR activities.

The present review describes research on novel natural isoquinoline alkaloids and their N-oxides isolated from different plant species. More than 200 biological active compounds have shown confirmed antimicrobial, antibacterial, antitumor, and other activities. The structures, origins, and reported biological activities of a selection of isoquinoline N-oxides alkaloids are reviewed.

Chemo- and bioinformatics resources for in silico drug discovery from medicinal plants beyond their traditional use: a critical review.

In silico approaches have been widely recognised to be useful for drug discovery. Here, we consider the significance of available databases of medicinal plants and chemo- and bioinformatics tools for in silico drug discovery beyond the traditional use of folk medicines. This review contains a practical example of the application of combined chemo- and bioinformatics methods to study pleiotropic therapeutic effects (known and novel) of 50 medicinal plants from Traditional Indian Medicine.

Collaborative development of predictive toxicology applications.

OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative) Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling.

Natural peroxy anticancer agents.

Present review describes research on novel natural anticancer agents isolated from terrestrial and marine sources. More than 120 cytotoxic anticancer compounds have shown confirmed activity in vitro tumor cell lines bioassay and are of current interest to Natural Cancer Institute for further in vivo evaluation. Intensive searches for new classes of pharmacologically potent agents produced by terrestrial and marine organisms have resulted in the discovery of dozens of compounds possessing high cytotoxic activities.

Novel antitumor agents: marine sponge alkaloids, their synthetic analogs and derivatives.

Present review describes research on novel natural antitumor agents isolated from marine sponges. More than 90 novel cytotoxic antitumor compounds and their synthetic analogs have shown confirmed activity in vitro tumor cell lines bioassay and are of current interest to NCI for further in vivo evaluation. A great problem, to use directly the reservoir of marine organisms for therapy is the very low availability and the isolation of only very small amounts of the biologically active substances from the natural materials.

PASS biological activity spectrum predictions in the enhanced open NCI database browser.

The application of the program PASS (Prediction of Activity Spectra for Substances) to about 250 000 compounds of the NCI Open Database and the incorporation of over 64 million PASS predictions in the Enhanced NCI Database Browser are described. A total of 565 different types of activity are included, encompassing general pharmacological effects, specific mechanisms of action, known toxicities, and others. Application of this Web-based service to prediction of activities of the kinds "Angiogenesis inhibitor," "Antiviral (HIV)", and a set of activities that can be associated with antineoplastic action are reported.