The chemical structures, and biological activities of marine terpenoids: a review and perspective from cheminformatics.

Fungi are a highly diverse group of heterotrophic organisms that play an important role in diverse ecological interactions, many of which are chemically mediated. Fungi have a very versatile metabolism, which allows them to synthesize a large number of still little-known chemical compounds, such as soluble compounds that are secreted into the medium and volatile compounds that are chemical mediators over short and long distances. Mass spectrometry (MS) is currently playing a dominant role in mycological studies, mainly due to its inherent sensitivity and rapid identification capabilities of different metabolites. Furthermore, MS has also been used as a reliable and accurate tool for fungi identification (i.e., biotyping). Here, we introduce the readers about fungal specialized metabolites, their role in ecological interactions and provide an overview on the MS-based techniques used in fungal studies. We particularly present the importance of sampling techniques, strategies to reduce false-positive identification and new MS-based analytical strategies that can be used in mycological studies, further expanding the use of MS in broader applications. Therefore, we foresee a bright future for mass spectrometry-based research in the field of mycology.

Chemical signaling plays an important role in ecological interactions, such as communication and predator-prey dynamics. Since sessile species cannot physically escape predators, many contain compounds that deter predation; however, it is largely unknown how predators physiologically detect deterrent chemicals. Few studies have investigated ecologically relevant aversive taste responses in any predator. Our objective was to determine if a signaling pathway for detecting marine sponge-derived deterrent compounds could be reconstituted in a heterologous expression system to ultimately facilitate investigation of the molecular mechanism of such an aversive behavioral response. Zebrafish (Danio rerio) rejected artificial diets laced with sponge chemical defense compounds that were previously shown to deter a generalist marine predator, Thalassoma bifasciatum, suggesting that zebrafish can recognize deterrent compounds relevant to coral reef systems. Transcripts made from a zebrafish cDNA library were expressed in a heterologous system, Xenopus laevis oocytes, and tested for chemoreceptor activation via electrophysiology, using the cystic fibrosis transmembrane conductance regulator (CFTR) as a reporter. Oocytes expressing gene sequences from the library and CFTR exhibited a CFTR-like electrophysiological response to formoside and ectyoplasides A and B, sponge defense compounds. Therefore, the chemical defense-activated signaling pathway can be reconstituted in Xenopus oocytes. Kinetics of the responses suggested that the responses to formoside and ectyoplasides A and B were receptor-mediated and capable of using the G(alphas) signaling pathway in this system. This bioassay has the potential to lead to the identification of genes that encode receptors capable of interacting with deterrent chemicals, which would enable understanding of predator detection of chemical defenses.

Plants contain numerous natural products (secondary metabolites) that may not participate directly in their growth and development but play an important role in ecological interactions with other organisms. Despite immense chemical diversity, which originates from simple carbohydrates produced because of photosynthesis, plant natural products are formed from only a few biosynthetic building blocks that consist of acetate, mevalonate, and shikimate. These basic building blocks undergo a variety of biosynthetic transformations and combinations that lead to numerous classes of plant natural products including, but not limited to, carbohydrates, fatty acids and their esters, aromatic polyketides (phenols and quinones), terpenoids and steroids, phenyl propanoids (lignans and lignin, coumarins, flavonoids, and isoflavonoids), and alkaloids. Summarized in this article are representative members of these important classes of plant natural products with special emphasis on their chemical diversity. The article concludes with a brief discussion on recent methods for the maximization of chemical diversity and the production of natural products from plants.

Marine organisms produce numerous secondary metabolites that exhibit a wide range of biological activities, which have applications in pharmaceutical research. Numerous secondary metabolites have been discovered from various marine organisms and studied for their chemical and biological properties. Among the secondary metabolites of marine organisms, alkaloids constitute a versatile group of bioactive natural products with promising bio-activities. Several alkaloids, such as pyridoacridines, pyrroles, bisindole, isoquinolines, quinolizidines and bromotyrosines, etc., to name a few, have been isolated from marine organisms. The chemical diversity and bio-activities of marine alkaloids are reported in several research and review articles. Quinolizidine alkaloids (QAs) are a group of compounds that possess either a quinolizidine ring or its derivatives. They are isolated from terrestrial plants, animals and also from numerous marine organisms, such as sponges, tunicates, fungus, etc. Biological activities exhibited by QAs include ichthyotoxicity, chemical defense, antimicrobial, antiviral, and inhibition of nicotinic acetylcholine receptors. In the past years, a few scattered reviews appeared on the isolation of QAs from natural sources, mostly from terrestrial sources, but the reports skipped several QAs of marine origin. This chapter presents a comprehensive review of various quinolizidine and bis-1-oxaquinolizidine alkaloids isolated from marine organisms, detailing their chemical structures and reported biological properties. Further, the chapter highlighted synthesis of some marine-derived QAs, namely, petrosins, xestospongins, clavepictines, pictamine, citrinadins A and B.

The main focus of this review is to introduce readers to the fascinating class of lipid molecules known as norsteroids, exploring their distribution across various biotopes and their biological activities. The review provides an in-depth analysis of various modified steroids, including A, B, C, and D-norsteroids, each characterized by distinct structural alterations. These modifications, which range from the removal of specific methyl groups to changes in the steroid core, result in unique molecular architectures that significantly impact their biological activity and therapeutic potential. The discussion on A, B, C, and D-norsteroids sheds light on their unique configurations and how these structural modifications influence their pharmacological properties. The review also presents examples from natural sources that produce a diverse array of steroids with distinct structures, including the aforementioned A, B, C, and D-nor variants. These compounds are sourced from marine organisms like sponges, soft corals, and starfish, as well as terrestrial entities such as plants, fungi, and bacteria. The exploration of these steroids encompasses their biosynthesis, ecological significance, and potential medical applications, highlighting a crucial area of interest in pharmacology and natural product chemistry. The review emphasizes the importance of researching these steroids for drug development, particularly in addressing diseases where conventional medications are inadequate or for conditions lacking sufficient therapeutic options. Examples of norsteroid synthesis are provided to illustrate the practical applications of this research.

Chemical signals play important roles in ecological interactions but are vulnerable to perturbation by air pollution. In polluted air masses, signals may travel shorter distances before being destroyed by chemical reactions with pollutants, thus losing their specificity. To determine which scent-mediated interactions are likely to be affected, we review existing literature to build a picture of what chemicals are commonly found in such interactions and the spatial scales at which interactions occur. We find that pollination, attraction of natural enemies of plant pests, aggregation pheromones, and mate attraction are likely to be affected. We review the scant literature on this topic and extend the hypothesis to include heretofore unexplored interactions. New research should investigate whether air pollution deleteriously affects populations of organisms that rely on scent plumes. Additionally, we need to investigate whether or not breakdown products created by the reaction of signaling chemicals with pollutants can provide usable signals, and whether or not there has been adaptation on the part of scent emitters or receivers to use either breakdown products or more robust chemical signals. The proposed research will necessarily draw on tools from atmospheric science, evolutionary biology, and ecology in furthering our understanding of the ecological implications of how air pollution modifies the scentscape.

An ecosystem model of the lower Po river for use in ecological risk assessment of xenobiotics

Non-indolyl cruciferous phytoalexins: Nasturlexins and tridentatols, a striking convergent evolution of defenses in terrestrial plants and marine animals?

Bioactive tetramic acid metabolites

Dictyostelium is a microorganism found in soils that are known as the battle fields of chemical warfare. Genome analysis of Dictyostelium revealed that it has great potential for the production of small molecules, including secondary metabolites such as polyketides and terpenes.Polyketides are a large family of secondary metabolites which have a variety of structures. In accordance with their structural variety, polyketides have a plethora of biological activities, including antimicrobial, antifungal, and antitumor activities. Unsurprisingly, they have exceptional medical importance. Polyketides in nature work as protective compounds and /or function in pheromonal communication. Terpenes belong to another family of structurally diverse secondary metabolites which play roles in ecological interactions, including defence against predators and formation of mutually beneficial alliance with other organisms. Polyketides and terpenes work as intra- or inter-species signalling compounds, i.e. they play the role of a chemical language. However, in Dictyostelium, they work as paracrine signalling compounds which control the organism's multicellular morphogenesis. This review is primarily focused on the small molecules that regulate pattern formation in the slug stage of the organism and their biosynthetic pathways. Current in vivo understandings of polyketide DIF-1 induced cell differentiation and DIF-1-dependent/independent pathways are also discussed.

Diabetes mellitus (DM), particularly type 2 diabetes (T2DM), remains a significant global health concern, driven largely by oxidative stress-induced damage. Marine terpenoids, bioactive compounds extracted from diverse marine organisms such as algae, sponges, and corals, present promising antioxidant and antidiabetic potential. This review systematically evaluates the chemical diversity, biological sources, and mechanisms of action of marine terpenoids in mitigating diabetes-associated oxidative stress. Marine terpenoids exhibit potent antioxidant capabilities via radical scavenging, modulation of cellular antioxidant defenses, regulation of redox-sensitive pathways such as Nrf2/ARE and NF-κB, metal chelation, and pro-oxidant enzyme inhibition. Preclinical studies underscore their efficacy in reducing hyperglycemia, enhancing insulin sensitivity, preserving pancreatic β-cell function, and protecting against diabetic complications, including nephropathy and cardiovascular diseases. Despite the promising preliminary results, further studies addressing bioavailability, pharmacokinetics, long-term safety, and sustainability are imperative to establish marine terpenoids as viable therapeutic options for diabetes management.

Polar marine biota have adapted to thrive under one of the ocean’s most inhospitable scenarios, where extremes of temperature, light photoperiod and ice disturbance, along with ecological interactions, have selected species with a unique suite of secondary metabolites. Organisms of Arctic and Antarctic oceans are prolific sources of natural products, exhibiting wide structural diversity and remarkable bioactivities for human applications. Chemical skeletons belonging to terpene families are the most commonly found compounds, whereas cytotoxic antimicrobial properties, the capacity to prevent infections, are the most widely reported activities from these environments. This review firstly summarizes the regulations on access and benefit sharing requirements for research in polar environments. Then it provides an overview of the natural product arsenal from Antarctic and Arctic marine organisms that displays promising uses for fighting human disease. Microbes, such as bacteria and fungi, and macroorganisms, such as sponges, macroalgae, ascidians, corals, bryozoans, echinoderms and mollusks, are the main focus of this review. The biological origin, the structure of terpenes and terpenoids, derivatives and their biotechnological potential are described. This survey aims to highlight the chemical diversity of marine polar life and the versatility of this group of biomolecules, in an effort to encourage further research in drug discovery.

Bio-mining the microbial treasures of the ocean: New natural products

Genetically encoded small molecules (secondary metabolites) play eminent roles in ecological interactions, as pathogenicity factors and as drug leads. Yet, these chemical mediators often evade detection, and the discovery of novel entities is hampered by low production and high rediscovery rates. These limitations may be addressed by genome mining for biosynthetic gene clusters, thereby unveiling cryptic metabolic potential. The development of sophisticated data mining methods and genetic and analytical tools has enabled the discovery of an impressive array of previously overlooked natural products. This review shows the newest developments in the field, highlighting compound discovery from unconventional sources and microbiomes.

Fungi are well-known producers of secondary metabolites, commonly referred to as exo-metabolites, which play crucial roles in ecological interactions, including plant protection. Among these metabolites, many exhibit potent antifungal properties, making them effective biocontrol agents against phytopathogenic fungi that cause significant agricultural losses. This study investigates the antifungal potential of solvent extracts derived from the extracellular secondary metabolites of Penicillium capsulatum, specifically targeting five phytopathogenic fungi: Fusarium equseti, Fusarium acuminatum, Colletotrichum gloeosporioides, Fusarium javanicum, and Nigrospora sphaeria. Using a solvent extraction method, partially purified fungal metabolites were tested for their antifungal activity via the pour plate method. The extracts were incorporated into agar medium in two concentrations: 100μl (lower dose) and 500μl (higher dose), and the growth reduction percentage was calculated based on the colony diameter measurements. The results indicated that the toluene extract of P. capsulatum exhibited the highest growth reduction against F. equseti, achieving 45.00 ± 3.54% at the higher dose and 37.50 ± 3.54% at the lower dose. The methanolic extract demonstrated complete inhibition (100.00 ± 0.00%) of F. acuminatum and C. gloeosporioides at the higher dose, while acetic acid, DMSO, and acetonitrile extracts showed varying levels of antifungal activity against other target pathogens. These findings highlight the potential of P. capsulatum metabolites as effective antifungal agents against diverse phytopathogenic fungi, presenting a promising alternative to chemical fungicides. Furthermore, the results support the need for further exploration of fungal metabolites in the development of sustainable biocontrol strategies for managing plant diseases.