The Arsenal of Bioactive Molecules in the Skin Secretion of Urodele Amphibians

Urodele amphibians (∼768 spp.), salamanders and newts, are a rich source of molecules with bioactive properties, especially those isolated from their skin secretions. These include pharmacological attributes, such as antimicrobial, antioxidant, vasoactive, immune system modulation, and dermal wound healing activities. Considering the high demand for new compounds to guide the discovery of new drugs to treat conventional and novel diseases, this review summarizes the characteristics of molecules identified in the skin of urodele amphibians. We describe urodele-derived peptides and alkaloids, with emphasis on their biological activities, which can be considered new scaffolds for the pharmaceutical industry. Although much more attention has been given to anurans, bioactive molecules produced by urodeles have the potential to be used for biotechnological purposes and stand as viable alternatives for the development of therapeutic agents.

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Investigation of a New Compound, B.W.203, and of Chlorpromazine in the Treatment of Psychosis

Journal of Mental Science ◽

10.1192/bjp.104.436.749 ◽

1958 ◽

Vol 104 (436) ◽

pp. 749-757 ◽

Cited By ~ 7

Author(s):

B. G. Fleming ◽

J. D. C. Currie

Keyword(s):

Mental Illness ◽

Scientific Theory ◽

Therapeutic Potential ◽

Therapeutic Agents ◽

New Drugs ◽

Clinical Test ◽

Empirical Methods ◽

Phenothiazine Derivatives ◽

Widespread Application ◽

New Compounds

The discovery of chlorpromazine in the Rhône-Poulenc-Spécia laboratories in France, and the subsequent early clinical studies which were carried out in that country, for example in 1952 by Hamon et al. (5) and in 1953 by Delay and Deniker (1), eventually resulted in the enthusiastic and widespread application of this compound in the field of clinical psychiatry. Chemists and pharmacologists, in many countries, have been actively engaged during the ensuing years in the search for new compounds which might prove to be more potent therapeutic agents than chlorpromazine in the treatment of mental illness. One of the tangible manifestations of their labours is the present crop of “tranquillizers” which are being extensively used in the treatment of neurosis and psychosis. Whereas opinion may be divided with regard to the real or specific value of any one of these new drugs, few would disagree with the contention that none of them is ideal. Despite the considerable number and variety of phenothiazine derivatives and other new substances which have been developed as a result of extensive research, chlorpromazine has retained much of its original therapeutic reputation, in open competition with its rivals, down the years, and is still probably the most widely used tranquillizer today. This would seem to imply that no outstanding advance has been made since the early days of the new biochemical era in psychiatry. Valuable knowledge may have been obtained as a result of the application of scientific theory and empirical methods in this field, but in terms of effective therapeutic agents the results have been meagre, with the accent on quantity rather than quality. Nevertheless, a continued search is justifiable, and any new compound which holds forth promise must be put to a clinical test if final success is to be assured and if valuable therapeutic potential is not to be summarily dismissed or heedlessly cast aside.

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Natural Sesquiterpene Lactones as Potential Trypanocidal Therapeutic Agents: A Review

Natural Product Communications ◽

10.1177/1934578x1601101036 ◽

2016 ◽

Vol 11 (10) ◽

pp. 1934578X1601101 ◽

Cited By ~ 2

Author(s):

Liliana V. Muschietti ◽

Jerónimo L. Ulloa

Keyword(s):

Natural Products ◽

Biological Activities ◽

Wide Spectrum ◽

Sesquiterpene Lactones ◽

Large Body ◽

Therapeutic Agents ◽

New Drugs ◽

Parasitic Diseases ◽

Marginalized Communities ◽

Allergic Contact

Chagas’ disease and Human African Trypanosomiasis are parasitic diseases that remain major health problems, mainly among the poorest and the most marginalized communities from Latin America and Africa. The scarcity of effective chemotherapy, due to the low investment in the research and development (R&D) of new drugs, together with a high incidence of side effects, and the emergence of drug resistance phenomena emphasize the urgent need for new prophylactic and therapeutic agents. Over the ages, humans have employed natural products to treat a wide spectrum of diseases. Recently, the pharmaceutical industry has focused on plant research and a large body of evidence has been collected to demonstrate the immense potential of medicinal plants as a source of bioactive compounds and lead molecules. In the field of parasitic diseases, drug development from plants has been successful for the sesquiterpene lactone (STL) artemisinin, which is employed as an antimalarial agent. STLs are a large group of naturally occurring terpenoids derived from plants that mostly belong to the Asteraceae family which exhibit a variety of skeletal arrangements and are the largest and most diverse category of natural products with an α-methylene-λ-lactone motif. STLs display a broad spectrum of biological activities such as antitumor, cytotoxic, antibacterial, anthelmintic, uterus contracting, antimalarial, neurotoxic, antiprotozoal and allergic (contact dermatitis) activities. In this context, the purpose of the present review is to provide an overview of the trypanocidal activity reported for STLs against Trypanosoma cruzi and T. brucei rhodesiense over the period 1993–2015.

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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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Preliminary investigation of the chemo diversity of bioactive molecules produced by endophytic fungi isolated from Manihot utilisima leaf

GSC Biological and Pharmaceutical Sciences ◽

10.30574/gscbps.2021.17.1.0284 ◽

2021 ◽

Vol 17 (1) ◽

pp. 011-025

Author(s):

Ugochukwu Moses Okezie ◽

Peter Maduabuchi Eze ◽

Festus Basden Chiedu Okoye ◽

Charles Okechukwu Esimone

Keyword(s):

Endophytic Fungi ◽

Antioxidant Activities ◽

Biological Activities ◽

Preliminary Investigation ◽

Antimicrobial Activities ◽

New Drugs ◽

Bioactive Molecules ◽

Fermentation Products ◽

Fungal Extract ◽

Wide Range

Endophytic fungi have demonstrated a harmless relationship living within the internal tissues of several plant hosts and at the same time produce diverse important bioactive compounds having a wide range of pharmaceutical applicability. In this study, nine endophytic fungi, eight from Cassava leaf: Clg1, Clg2, Clr4, Clr5, Clr6, Clr7, Clr9 and one from Cassava mid-rib: CRs3 with distinct cultural features were isolated from healthy leaves of Manihot utilisima and axenic cultures were fermented on sterile rice medium for 21 days. The antimicrobial and antioxidant activities of the fungal crude extracts were evaluated. Chemical analyses of the metabolic profiles of each fungal extract revealed the presence of nine known compounds with established biological activities. Each fungal extract exhibited antimicrobial activities against at least one Gram positive and Gram negative bacteria with an inhibition zone that ranged from 2 – 6 mm. Clg2 and CRs3 fungal extracts demonstrated moderate potential to scavenge free radical with an inhibition of 58 and 60% respectively. Septicine, cyclo(prolylvalyl), pentenedioc acid, neurolenin B, rubrofusarin, p-Hydroxybenzoic acid, protocatechuic acid, citreoisocoumarin, palitantin and pestalio pyrone were the compounds detected in the fungal fermentation products. Our findings reveal that M. utilisima leaves harbor endophytic fungi with unique chemodiversity of bioactive secondary metabolites needed for development of new drugs.

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Toxins Are an Excellent Source of Therapeutic Agents against Cardiovascular Diseases

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0038-1661384 ◽

2018 ◽

Vol 44 (07) ◽

pp. 691-706 ◽

Cited By ~ 9

Author(s):

Cho Yeow Koh ◽

Cassandra Modahl ◽

Namrata Kulkarni ◽

R. Manjunatha Kini

Keyword(s):

Cardiovascular Diseases ◽

Biological Activities ◽

Antiplatelet Agents ◽

Therapeutic Agents ◽

Bioactive Molecules ◽

Function Mechanism ◽

Physiological Processes ◽

Self Defense ◽

Diagnostic Agents ◽

Proteins And Peptides

AbstractVenomous and hematophagous animals use their venom or saliva for survival, to obtain food, and for self-defense. Venom and saliva from these animals are cocktails of bioactive molecules primarily composed of proteins and peptides. These molecules are called toxins because they cause unwanted consequences on prey. They exhibit unique, diverse, and specific biological activities that perturb normal physiological processes of their prey and host. However, the potential of toxins as inspirations for the development of therapeutic agents or pharmacological tools has also long been recognized. In addition to their small size, the exquisite selectivity and structural stability of toxins make them attractive as starting molecule in the development of therapeutic and diagnostic agents. Drug discovery and development from venomous and hematophagous animals against cardiovascular diseases have been particularly successful. Some of the notable success include antihypertensive (captopril and enalapril) and antiplatelet agents (tirofiban and eptifibatide), as well as anticoagulants (lepirudin and bivalirudin). Highlighted in this review are many venom or saliva-derived cardiovascular-active proteins and peptides of therapeutic interest, including those that are currently in preclinical stages and those that have been approved by FDA and currently in the market. The authors attempt to summarize their structure, function, mechanism of action, and development with respect to cardiovascular diseases.

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Alkaloid Profiling and Cholinesterase Inhibitory Potential of Crinum × amabile Donn. (Amaryllidaceae) Collected in Ecuador

Plants ◽

10.3390/plants10122686 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2686

Author(s):

Luciana R. Tallini ◽

Angelo Carrasco ◽

Karen Acosta León ◽

Diego Vinueza ◽

Jaume Bastida ◽

...

Keyword(s):

Inhibitory Activity ◽

Biological Activities ◽

New Drugs ◽

Bioactive Molecules ◽

Acetylcholinesterase Inhibition ◽

Plant Family ◽

Disease Symptoms ◽

Amaryllidaceae Alkaloids ◽

Inhibitory Potential

Natural products are one of the main sources for developing new drugs. The alkaloids obtained from the plant family Amaryllidaceae have interesting structures and biological activities, such as acetylcholinesterase inhibition potential, which is one of the mechanisms used for the palliative treatment of Alzheimer’s disease symptoms. Herein we report the alkaloidal profile of bulbs and leaves extracts of Crinum × amabile collected in Ecuador and their in vitro inhibitory activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Using Gas Chromatography coupled to Mass Spectrometry (GC-MS), we identified 12 Amaryllidaceae alkaloids out of 19 compounds detected in this species. The extracts from bulbs and leaves showed great inhibitory activity against AChE and BuChE, highlighting the potential of Amaryllidaceae family in the search of bioactive molecules.

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A comprehensive review on pyranoindole-containing agents

Current Medicinal Chemistry ◽

10.2174/0929867328666211206111058 ◽

2021 ◽

Vol 28 ◽

Author(s):

Alessia Catalano ◽

Domenico Iacopetta ◽

Jessica Ceramella ◽

Carmela Saturnino ◽

Maria Stefania Sinicropi

Keyword(s):

Natural Products ◽

Heterocyclic Compounds ◽

Biological Activities ◽

Therapeutic Agents ◽

Biologically Active ◽

Bioactive Molecules ◽

Structural Motif ◽

Huge Number ◽

Naturally Occurring ◽

Active Natural

: A huge number of nitrogen-containing heterocyclic compounds are ubiquitous in natural products, pharmaceuticals, and bioactive molecules. Among these, the pyranoindole represents an important structural motif, as it constitutes the central subunit in both the biologically active natural products and therapeutic agents. Talathermophilins, notoamides, norgeamides, carneamides, and versicamides are examples of naturally occurring pyranoindoles, while the well-known etodolac and pemedolac are a tetrahydropyrano[3,4-b]indole deriving from synthetic procedures. Besides the well-known antiinflammatory and fibrinolytic activity, molecules comprising the pyranoindole framework have been demonstrated to exhibit various biological activities, such as antiulcer, antidepressant, analgesic, and antiproliferative. Herein, we report the most common natural and synthetic products bearing a pyranoindole nucleus, their syntheses, and biological activities.

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Phytochemicals in Prostate Cancer: From Bioactive Molecules to Upcoming Therapeutic Agents

Nutrients ◽

10.3390/nu11071483 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1483 ◽

Cited By ~ 9

Author(s):

Salehi ◽

Fokou ◽

Yamthe ◽

Tali ◽

Adetunji ◽

...

Keyword(s):

Prostate Cancer ◽

Phenolic Compounds ◽

Therapeutic Agents ◽

New Drugs ◽

Bioactive Molecules ◽

Bioactive Constituents ◽

Naturally Occurring ◽

Potential Sources ◽

Prostate Cancers

Prostate cancer is a heterogeneous disease, the second deadliest malignancy in men and the most commonly diagnosed cancer among men. Traditional plants have been applied to handle various diseases and to develop new drugs. Medicinal plants are potential sources of natural bioactive compounds that include alkaloids, phenolic compounds, terpenes, and steroids. Many of these naturally-occurring bioactive constituents possess promising chemopreventive properties. In this sense, the aim of the present review is to provide a detailed overview of the role of plant-derived phytochemicals in prostate cancers, including the contribution of plant extracts and its corresponding isolated compounds.

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Synthesis and antifungal activity of new O-alkylamidoximes

Bioscience Journal ◽

10.14393/bj-v37n0a2021-54171 ◽

2021 ◽

Vol 37 ◽

pp. e37049

Author(s):

Maria Verônica Sales Barbosa ◽

Alana Karoline Penha Nascimento ◽

Rodrigo Ribeiro Alves Caiana ◽

Cosme Silva Santos ◽

Wylly Araújo Oliveira ◽

...

Keyword(s):

Antifungal Activity ◽

Antifungal Agents ◽

Therapeutic Agents ◽

New Drugs ◽

Moderate Activity ◽

Relevant Issue ◽

New Class ◽

Microdilution Method ◽

Broth Microdilution Method ◽

New Compounds

The continuous prospection for molecules that may be useful in the development of new therapeutic agents is a highly relevant issue, mainly because the launch of new drugs on the market does not accompany the emergence of new resistant microorganisms. In this context, this work describes the synthesis of new O-alkylamidoximes and the evaluation of its antifungal activity. The new O-alkylamidoximes were prepared using easy synthetic protocols and tested against three Candida species using the broth microdilution method. The synthesized compounds were obtained in moderate to good yields in high purity and without any observable decomposition. All tested compounds shown moderate antifungal activity against at least one strain of Candida. Despite the moderate activity of the new compounds, this was the first report involving the antifungal activity of O-alkylamidoximes. In view of the low chemotherapy arsenal and the development of fungal strains resistant to traditional antifungal agents, the present study opens new possibilities for the preparation of a new class of more active antifungal agents.

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A common mechanism links activities of butyrate in the colon

10.26434/chemrxiv.5414065.v1 ◽

2017 ◽

Author(s):

Mohit S. Verma ◽

Michael J. Fink ◽

Gabriel L Salmon ◽

Nadine Fornelos ◽

Takahiro E. Ohara ◽

...

Keyword(s):

Stem Cells ◽

Histone Deacetylases ◽

Biological Activities ◽

Short Chain Fatty Acids ◽

Common Mechanism ◽

Epithelial Stem Cells ◽

Degree Of Unsaturation ◽

Structure Activity ◽

Starting Point ◽

New Compounds

Two biological activities of butyrate in the colon (suppression of proliferation of colonic epithelial stem cells and inflammation) correlate with inhibition of histone deacetylases. Cellular and biochemical studies of molecules similar in structure to butyrate, but different in molecular details (functional groups, chain-length, deuteration, oxidation level, fluorination, or degree of unsaturation) demonstrated that these activities were sensitive to molecular structure, and were compatible with the hypothesis that butyrate acts by binding to the Zn<sup>2+</sup> in the catalytic site of histone deacetylases. Structure-activity relationships drawn from a set of 36 compounds offer a starting point for the design of new compounds targeting the inhibition of histone deacetylases. The observation that butyrate was more potent than other short-chain fatty acids is compatible with the hypothesis that crypts evolved (at least in part), to separate stem cells at the base of crypts from butyrate produced by commensal bacteria.

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