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Currently, there is an urgent need for new antibacterial and antifungal agents to combat the growing challenge of antibiotic resistance. As the largest ecosystem on Earth, the marine ecosystem includes a vast array of microorganisms (primarily bacteria and fungi), plants, invertebrates, and vertebrates, making it a rich source of various antimicrobial compounds. Notably, terpenoids, known for their complex structures and diverse bioactivities, are a significant and promising group of compounds in the battle against bacterial and fungal infections. In the past five years, numerous antimicrobial terpenoids have been identified from marine organisms such as bacteria, fungi, algae, corals, sea cucumbers, and sponges. This review article provides a detailed overview of 141 terpenoids with antibacterial and/or antifungal properties derived from marine organisms between 2019 and 2024. Terpenoids, a diverse group of natural organic compounds derived from isoprene units, are systematically categorized based on their carbon skeleton structures. Comprehensive information is provided about their names, structures, biological sources, and the extent of their antibacterial and/or antifungal effectiveness. This review aims to facilitate the rapid identification and development of prospective antimicrobials in the pharmaceutical sector.
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Organismos Acuáticos , Terpenos , Terpenos/farmacología , Terpenos/química , Animales , Antiinfecciosos/farmacología , Antiinfecciosos/química , Bacterias/efectos de los fármacos , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Hongos/efectos de los fármacos , Antifúngicos/farmacología , Antifúngicos/químicaRESUMEN
To better assess the practical value and avoid potential risks of the traditionally medicinal and edible basidiomycete Schizophyllum commune, which may arise from undescribed metabolites, a combination of elicitors was introduced for the first time to discover products from cryptic and low-expressed gene clusters under laboratory cultivation. Treating S. commune NJFU21 with the combination of five elicitors led to the upregulated production of a class of unusual linear diterpene-derived variants, including eleven new ones (1-11), along with three known ones (12-14). The structures and stereochemistry were determined by 1D and 2D NMR, HRESIMS, ECD, OR and VCD calculations. Notably, the elongation terminus of all the diterpenes was decorated by an unusual butenedioic acid moiety. Compound 1 was a rare monocyclic diterpene, while 2-6 possessed a tetrahydrofuran moiety. The truncated metabolites 4, 5 and 13 belong to the trinorditerpenes. All the diterpenes displayed approximately 70% scavenging of hydroxyl radicals at 50 µM and null cytotoxic activity at 10 µM. In addition, compound 1 exhibited potent antifungal activity against the plant pathogenic fungi Colletotrichum camelliae, with MIC values of 8 µg/mL. Our findings indicated that this class of diterpenes could provide valuable protectants for cosmetic ingredients and the lead compounds for agricultural fungicide development.
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Diterpenos , Schizophyllum , Diterpenos/farmacología , Diterpenos/química , Diterpenos/metabolismo , Schizophyllum/metabolismo , Schizophyllum/genética , Estructura Molecular , Regulación hacia Arriba/efectos de los fármacos , HumanosRESUMEN
Terpenoid alkaloids are recognized as a class of compounds with limited numbers but potent biological activities, primarily derived from plants, with a minor proportion originating from animals and microorganisms. These alkaloids are synthesized from the same prenyl unit that forms the terpene skeleton, with the nitrogen atom introduced through ß-aminoethanol, ethylamine, or methylamine, leading to a range of complex and diverse structures. Based on their skeleton type, they can be categorized into monoterpenes, sesquiterpenes, diterpenes, and triterpene alkaloids. To date, 289 natural terpenoid alkaloids, excluding triterpene alkaloids, have been identified in studies published between 2019 and 2024. These compounds demonstrate a spectrum of biological activities, including anti-inflammatory, antitumor, antibacterial, analgesic, and cardioprotective effects, making them promising candidates for further development. This review provides an overview of the sources, chemical structures, and biological activities of natural terpenoid alkaloids, serving as a reference for future research and applications in this area.
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Alcaloides , Terpenos , Alcaloides/química , Alcaloides/farmacología , Terpenos/química , Terpenos/farmacología , Humanos , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Estructura MolecularRESUMEN
Diterpenes represent one of the most diverse and structurally complex families of natural products. Among the myriad of diterpenoids, grayanane diterpenes are particularly notable. These terpenes are characterized by their unique 5/7/6/5 tetracyclic system and are exclusive to the Ericaceae family of plants. Renowned for their complex structures and broad spectrum of bioactivities, grayanane diterpenes have become a primary focus in extensive phytochemical and pharmacological research. Recent studies, spanning from 2018 to January 2024, have reported a series of new grayanane diterpenes with unprecedented carbon skeletons. These compounds exhibit various biological properties, including analgesic, antifeedant, anti-inflammatory, and inhibition of protein tyrosine phosphatase 1B (PTP1B). This paper delves into the discovery of 193 newly identified grayanoids, representing 15 distinct carbon skeletons within the Ericaceae family. The study of grayanane diterpenes is not only a deep dive into the complexities of natural product chemistry but also an investigation into potential therapeutic applications. Their unique structures and diverse biological actions make them promising candidates for drug discovery and medicinal applications. The review encompasses their occurrence, distribution, structural features, and biological activities, providing invaluable insights for future pharmacological explorations and research.
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Productos Biológicos , Diterpenos , Ericaceae , Diterpenos/farmacología , Terpenos , Productos Biológicos/farmacología , CarbonoRESUMEN
Artabotrys, a pivotal genus within the Annonaceae family, is renowned for its extensive biological significance and medicinal potential. The genus's sesquiterpene compounds have attracted considerable interest from the scientific community due to their structural complexity and diverse biological activities. These compounds exhibit a range of biological activities, including antimalarial, antibacterial, anti-inflammatory analgesic, and anti-tumor properties, positioning them as promising candidates for medical applications. This review aims to summarize the current knowledge on the variety, species, and structural characteristics of sesquiterpene compounds isolated from Artabotrys plants. Furthermore, it delves into their pharmacological activities and underlying mechanisms, offering a comprehensive foundation for future research.
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Annonaceae , Antimaláricos , Sesquiterpenos , Antibacterianos , Antiinflamatorios no Esteroideos , Antimaláricos/farmacología , Sesquiterpenos/farmacologíaRESUMEN
Sepsis-induced acute lung injury (ALI), characterized by widespread lung dysfunction, is associated with significant morbidity and mortality due to the lack of effective pharmacological treatments available clinically. Small-molecule compounds derived from natural products represent an innovative source and have demonstrated therapeutic potential against sepsis-induced ALI. These natural small molecules may provide a promising alternative treatment option for sepsis-induced ALI. This review aims to summarize the pathogenesis of sepsis and potential therapeutic targets. It assembles critical updates (from 2014 to 2024) on natural small molecules with therapeutic potential against sepsis-induced ALI, detailing their sources, structures, effects, and mechanisms of action.
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Pain is often debilitating, and current treatments are neither universally efficacious nor without risks. Transient receptor potential (TRP) ion channels offer alternative targets for pain relief, but little is known about the regulation or identities of endogenous TRP ligands that affect inflammation and pain. Here, transcriptomic and targeted lipidomic analysis of damaged tissue from the mouse spinal nerve ligation (SNL)-induced chronic pain model revealed a time-dependent increase in Cyp1b1 mRNA and a concurrent accumulation of 8,9-epoxyeicosatrienoic acid (EET) and 19,20-EpDPA post injury. Production of 8,9-EET and 19,20-EpDPA by human/mouse CYP1B1 was confirmed in vitro, and 8,9-EET and 19,20-EpDPA selectively and dose-dependently sensitized and activated TRPA1 in overexpressing HEK-293 cells and Trpa1-expressing/AITC-responsive cultured mouse peptidergic dorsal root ganglia (DRG) neurons. TRPA1 activation by 8,9-EET and 19,20-EpDPA was attenuated by the antagonist A967079, and mouse TRPA1 was more responsive to 8,9-EET and 19,20-EpDPA than human TRPA1. This latter effect mapped to residues Y933, G939, and S921 of TRPA1. Intra-plantar injection of 19,20-EpDPA induced acute mechanical, but not thermal hypersensitivity in mice, which was also blocked by A967079. Similarly, Cyp1b1-knockout mice displayed a reduced chronic pain phenotype following SNL injury. These data suggest that manipulation of the CYP1B1-oxylipin-TRPA1 axis might have therapeutic benefit.
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We report the identification of the tnd biosynthetic cluster from the marine-derived fungus Aspergillus flavipes and the in vivo characterization of a cryptic type I diterpene synthase. The heterologous expression of the bifunctional terpene synthase led to the discovery of a diterpene backbone, talarodiene, harboring a benzo[a]cyclopenta[d]cyclooctane tricyclic fused ring system. The conversion of geranylgeranyl diphosphate to talarodiene was investigated using 13C-labeling studies, and stable isotope tracer experiments showed the biotransformation of talarodiene into talaronoid C.
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Transferasas Alquil y Aril , Aspergillus , Diterpenos , Transferasas Alquil y Aril/metabolismo , Organismos Acuáticos/enzimología , Aspergillus/enzimología , Ciclooctanos , Diterpenos/metabolismo , Fosfatos de Poliisoprenilo/químicaRESUMEN
In a program to identify pain treatments with low addiction potential, we isolated five steroids, conosteroids A-E (1-5), from the hypobranchial gland of the mollusk Conus geographus. Compounds 1-5 were active in a mouse dorsal root ganglion (DRG) assay that suggested that they might be analgesic. A synthetic analogue 6 was used for a detailed pharmacological study. Compound 6 significantly increased the pain threshold in mice in the hot-plate test at 2 and 50 mg/kg. Compound 6 at 500 nM antagonizes type-A γ-aminobutyric acid receptors (GABAARs). In a patch-clamp experiment, out of the six subunit combinations tested, 6 exhibited subtype selectivity, most strongly antagonizing α1ß1γ2 and α4ß3γ2 receptors (IC50 1.5 and 1.0 µM, respectively). Although the structures of 1-6 differ from those of known neuroactive steroids, they are cell-type-selective modulators of GABAARs, expanding the known chemical space of neuroactive steroids.
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Analgésicos/química , Caracol Conus/química , Antagonistas del GABA/química , Neuroesteroides/química , Receptores de GABA/química , Potenciales de Acción/efectos de los fármacos , Analgésicos/síntesis química , Analgésicos/farmacología , Analgésicos/uso terapéutico , Animales , Caracol Conus/metabolismo , Modelos Animales de Enfermedad , Antagonistas del GABA/aislamiento & purificación , Antagonistas del GABA/farmacología , Antagonistas del GABA/uso terapéutico , Ganglios Espinales/citología , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/fisiología , Ratones , Ratones Endogámicos C57BL , Conformación Molecular , Neuroesteroides/aislamiento & purificación , Neuroesteroides/farmacología , Neuroesteroides/uso terapéutico , Dolor/inducido químicamente , Dolor/tratamiento farmacológico , Dolor/patología , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , Receptores de GABA/metabolismoRESUMEN
Venomous molluscs (Superfamily Conoidea) comprise a substantial fraction of tropical marine biodiversity (>15,000 species). Prior characterization of cone snail venoms established that bioactive venom components used to capture prey, defend against predators and for competitive interactions were relatively small, structured peptides (10-35 amino acids), most with multiple disulfide crosslinks. These venom components ("conotoxins, conopeptides") have been widely studied in many laboratories, leading to pharmaceutical agents and probes. In this review, we describe how it has recently become clear that to varying degrees, cone snail venoms also contain bioactive non-peptidic small molecule components. Since the initial discovery of genuanine as the first bioactive venom small molecule with an unprecedented structure, a broad set of cone snail venoms have been examined for non-peptidic bioactive components. In particular, a basal clade of cone snails (Stephanoconus) that prey on polychaetes produce genuanine and many other small molecules in their venoms, suggesting that this lineage may be a rich source of non-peptidic cone snail venom natural products. In contrast to standing dogma in the field that peptide and proteins are predominantly used for prey capture in cone snails, these small molecules also contribute to prey capture and push the molecular diversity of cone snails beyond peptides. The compounds so far characterized are active on neurons and thus may potentially serve as leads for neuronal diseases. Thus, in analogy to the incredible pharmacopeia resulting from studying venom peptides, these small molecules may provide a new resource of pharmacological agents.
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Calcium homeostasis is implicated in some cancers, leading to the possibility that selective control of calcium might lead to new cancer drugs. On the basis of this idea, we designed an assay using a glioblastoma cell line and screened a collection of 1000 unique bacterial extracts. Isolation of the active compound from a hit extract led to the identification of boholamide A (1), a 4-amido-2,4-pentadieneoate (APD)-class peptide. Boholamide A (1) applied in the nanomolar range induces an immediate influx of Ca2+ in glioblastoma and neuronal cells. APD-class natural products are hypoxia-selective cytotoxins that primarily target mitochondria. Like other APD-containing compounds, 1 is hypoxia selective. Since APD natural products have received significant interest as potential chemotherapeutic agents, 1 provides a novel APD scaffold for the development of new anticancer compounds.
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Antineoplásicos/farmacología , Productos Biológicos/farmacología , Calcio/metabolismo , Citotoxinas/farmacología , Depsipéptidos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Calcio/química , Citotoxinas/química , Depsipéptidos/química , Depsipéptidos/aislamiento & purificación , Hipoxia/fisiopatología , Estructura Molecular , NeoplasiasRESUMEN
Seven new diterpenoids, including four ent-kaurane-type pierisentkaurans B-E (1-4), one 4,5-seco- ent-kaurane-type pierisentkauran F (5), two leucothane-type 3ß,7α,14ß-trihydroxy-leucoth-10(20),15-dien-5-one (6) and 10α,16α-dihydroxy-leucoth-5-one (7), along with three known diterpenoids ent-kaurane-type 16α-dihydroxy-6-oxo-ent-kauran-18-oic-acid (8), kalmane-type rhodomollein XXIII (9), and grayanane-type pierisformosoid J (10), were isolated from the roots of Pieris formosa. Their structures with absolute configurations were determined by a series of spectroscopic methods and electronic circular dichroism (ECD) calculations. Compounds 2 and 7 displayed weak analgesic activity at a dose of 5.0 mg/kg (i.p.) compared to the vehicle tests (p < 0.05) in an acetic acid-induced writhing test. At a dose of 0.5 mg/mL, compounds 3 and 7 showed antifeedant activity against Plutella xylostella larvae with inhibition ratios of 27.1% and 52.5%, respectively.
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Analgésicos/farmacología , Diterpenos/farmacología , Ericaceae/química , Conducta Alimentaria/efectos de los fármacos , Dolor/tratamiento farmacológico , Raíces de Plantas/química , Ácido Acético , Analgésicos/química , Analgésicos/aislamiento & purificación , Animales , Diterpenos/química , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Estructura Molecular , Mariposas Nocturnas , Dolor/inducido químicamente , Relación Estructura-ActividadRESUMEN
Six new glycosides (1-6), together with three known ones, were isolated from the twigs and leaves of Rhododendron latoucheae. Their structures were elucidated based on the spectroscopic data, including infrared spectrometry, mass spectrometry, and nuclear magnetic resonance experiments, along with Mosher's method. In addition, all compounds were tested their antiviral (herpes simplex virus-1 and influenza A/95-359) activities.
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Glicósidos/aislamiento & purificación , Rhododendron/química , Antivirales/farmacología , Glicósidos/química , Glicósidos/farmacología , Espectroscopía de Resonancia Magnética , Hojas de la Planta/químicaRESUMEN
In our on-going study to investigate components with analgesic activity, eight new grayanane diterpenoids, epoxypieristoxins A-H (1-8), along with one known compound (9) were isolated from the roots of Pieris formosa. Their structures with absolute configurations were characterized by a series of spectroscopic methods and X-ray diffraction. Notably, compounds 1-5 represented the first example of natural grayanane diterpenoids possessed a 10,14-epoxy group. Whereas, compounds 6-7 were the first example of grayanane diterpenoid with a 7,10-epoxy group. Biological assays showed that compounds 1-3 and 5-8 displayed significant analgesic activity at a dose of 5.0â¯mg/kg (ip) compared to the vehicle tests (pâ¯<â¯.05).
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Analgésicos/farmacología , Diterpenos/farmacología , Ericaceae/química , Raíces de Plantas/química , Analgésicos/aislamiento & purificación , Animales , Diterpenos/aislamiento & purificación , Ratones , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacologíaRESUMEN
A hyphenated NMR technique (analytical HPLC with a DAD connected to MS, SPE, and NMR) has proven effective for the full structural analysis and identification of minor natural products in complex mixtures. Application of this hyphenated technique to the CH2Cl2-soluble fraction of Rhododendron latoucheae led to the identification of 15 new minor ursane-type 28-nortriterpenoids (1-15). Compounds 1 and 12 inhibited HSV-1 with IC50 values of 6.4 and 0.4 µM, respectively.
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Componentes Aéreos de las Plantas/química , Hojas de la Planta/química , Rhododendron/química , Triterpenos/química , Animales , Antivirales/química , Antivirales/farmacología , Chlorocebus aethiops , Cromatografía Líquida de Alta Presión , Perros , Herpesvirus Humano 1/efectos de los fármacos , Virus de la Influenza A/efectos de los fármacos , Células de Riñón Canino Madin Darby , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura Molecular , Extractos Vegetales/química , Extracción en Fase Sólida , Triterpenos/farmacología , Células VeroRESUMEN
By the means of chromatographic methods and spectroscopic evidences, 7 diterpenoids were isolated and identified from the roots of Pieris formosa. These known compounds are elucidated as secorhodomollolide C(1), pierisoid B (2), secorhodomollolide B (3), secorhodomollolide A (4), pierisformotoxin G (5), pierisformotoxin B (6) and pierisformotoxin A (7). Compounds 3, 4 were obtained from this plant for the first time. The analgesic activities of compounds 1-7 were evaluated using an acetic acidinduced writhing test in mice. Compounds 3, 4, 6, and 7 exhibited significant analgesic activity at 5 mg·kg;â» (ip) compared to vehicle-injected mice (P<0.05). The writhe inhibition rates of compounds 3, 4, 6 and 7 at 5 mg·kg⻹ (ip) were 41.3%, 39.4%, 38.6% and 37.5%, respectively.
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Analgésicos/farmacología , Diterpenos/farmacología , Ericaceae/química , Raíces de Plantas/química , Analgésicos/aislamiento & purificación , Animales , Diterpenos/aislamiento & purificación , Ratones , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacologíaRESUMEN
Rhodoterpenoids AâC (1â3), three new rearranged triterpenoids, together with one new biogenetically related compound, rhodoterpenoid D (4), were isolated and efficiently elucidated from Rhododendron latoucheae by high-performance liquid chromatography-mass spectrometry-solid-phase extraction-nuclear magnetic resonance (HPLCâMSâSPEâNMR). Compounds 1 and 2 possess an unprecedented skeleton with a 5/7/6/6/6-fused pentacyclic ring system, while compound 3 contains a unique 6/7/6/6/6-fused pentacyclic carbon backbone. Their structures were determined by extensive spectroscopic methods and electronic circular dichroism (ECD) analyses. Plausible biogenetic pathways for 1â4 were proposed. Compounds 1 and 4 showed potential activity against herpes simplex virus 1 (HSV-1) with IC50 values of 8.62 and 6.87 µM, respectively.
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Antivirales/química , Herpesvirus Humano 1/efectos de los fármacos , Rhododendron/química , Triterpenos/química , Animales , Antivirales/aislamiento & purificación , Antivirales/farmacología , Chlorocebus aethiops , Cromatografía Líquida de Alta Presión , Dicroismo Circular , Concentración 50 Inhibidora , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Extracción en Fase Sólida , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Células VeroRESUMEN
Pierisketolide A (1) and pierisketones B and C (2 and 3), three diterpenes with an unusual A-homo-B-nor-ent-kaurane carbon skeleton, were isolated from the roots of Pieris formosa. Their structures were characterized by a series of spectroscopic methods, X-ray diffraction, and electronic circular dichroism (ECD). Pierisketolide A (1) exhibited an analgesic effect with a 45% writhe inhibition rate at a dose of 10.0 mg/kg. The plausible biosynthetic pathways of 1-3 are proposed.
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Analgésicos/química , Diterpenos/química , Extractos Vegetales/química , Raíces de Plantas/química , Tracheophyta/química , Analgésicos/aislamiento & purificación , Carbono/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Humanos , Estructura Molecular , Extractos Vegetales/aislamiento & purificación , Relación Estructura-ActividadRESUMEN
Ten compounds, including seven sesquiterpenes, two phenols and one phenylpropanoid, were isolated from the roots of Illicium majus by means of silica gel, ODS, Sephadex LH-20, and preparative HPLC. On analysis of MS and NMR spectroscopic data , their structures were established as cycloparviflorolide (1), cycloparvifloralone (2), tashironin (3), tashironin A (4), anislactone A(5), anislactone B (6), pseudomajucin (7), syringaldehyde (8), methyl-4-hydroxy-3, 5-dimethoxybenzoate (9), and (E)-3-methoxy-4,5-methylenedioxycinnamic alchol (10), respectively. Compounds 1-4 and 8-10 were first isolated from this plant. In the in vitro assays, at a concentration of 1.0 x 10(-5) mol x L(-1), compounds 5 and 6 were active against LPS induced NO production in microglia with a inhibition rate of 75.31% and 53.7%, respectively.
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Medicamentos Herbarios Chinos/análisis , Illicium/química , Compuestos Orgánicos/análisis , Raíces de Plantas/química , Medicamentos Herbarios Chinos/química , Compuestos Orgánicos/químicaRESUMEN
The chemical constituents of Vaccinium bracteatum were studied by means of macroporous resin, ODS column chromatography and preparative HPLC. Eleven compounds were isolated from this plant. By using ESI-MS and NMR, the structures of the eleven compounds were determined as 10-O-trans-p-coumaroyl-6alpha-hydroxyl-dihydromonotropein (1), 10-O-cis-p-coumaroyl -6alpha-hydroxyl-dihydromonotropein (2), vaccinoside (3), 10-O-cis-p-coumaroyl monotropein (4), isolariciresinol-9-O-beta-D-xyloside (5), tectoridin (6), vicenin-3 (7), quercetin-3-O-alpha-L-rhamnoside (8), quercetin-3-O-alpha-L-arabinopyranoside (9), quercetin-3-O-beta-D-galactopyranoside (10), and quercetin-3-O-beta-D-glucuronide (11), respectively. Compounds 1 and 2 are new, and compounds 4, 6 and 7 are isolated from the genus Vaccinium for the first time.