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1.
J Agric Food Chem ; 72(19): 10970-10980, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38708787

RESUMEN

Eleven alkaloids (1-11) including seven new ones, 1-7, were isolated from the solid fermentation of Aspergillus fumigatus VDL36, an endophytic fungus isolated from the leaves of Vaccinium dunalianum Wight (Ericaceae), a perennial evergreen shrub distributed across the Southwest regions of China, Myanmar, and Vietnam. Their structures were elucidated on the basis of extensive spectroscopic methods. The isolates were evaluated for in vitro antifungal activities against five phytopathogenic fungi (Fusarium oxysporum, Coriolus versicolor, Fusarium solani, Botrytis cinerea, Fusarium graminearum). As a result, the new compounds fumigaclavine I (1), 13-ethoxycyclotryprostatin A (5), 13-dehydroxycyclotryprostatin A (6), and 12ß-hydroxy-13-oxofumitremorgin C (7) exhibited antifungal activities with MIC values of 7.8-62.5 µg/mL which were comparable to the two positive controls ketoconazole (MIC = 7.8-31.25 µg/mL) and carbendazim (MIC = 1.95-7.8 µg/mL). Furthermore, compounds 1 and 5 demonstrated potent protective and curative effects against the tomato gray mold in vivo. Preliminary structure-activity relationships of the tested indole diketopiperazine alkaloids indicate that the introduction of a substituent group at position C-13 enhances their biological activities.


Asunto(s)
Alcaloides , Aspergillus fumigatus , Endófitos , Alcaloides/farmacología , Alcaloides/química , Aspergillus fumigatus/efectos de los fármacos , Endófitos/química , Estructura Molecular , Fusarium/efectos de los fármacos , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Hojas de la Planta/microbiología , Hojas de la Planta/química , Pruebas de Sensibilidad Microbiana , China , Enfermedades de las Plantas/microbiología
2.
Sci Rep ; 14(1): 10424, 2024 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-38710752

RESUMEN

The storage process has a significant impact on tea quality. Few is known about effect of storage on quality of oolong tea. This study aimed to assess the effect of different storage times on the key chemical components of oolong tea by measuring changes in catechin, free amino acid, and alkaloid content. Variation in the main substances was determined by principal component analysis and heat map analysis. The results revealed notable effects of the storage process on the levels of theanine, epigallocatechin gallate (EGCG), and glutamine. These findings suggest that these compounds could serve as indicators for monitoring changes in oolong tea quality during storage. Additionally, the study observed an increase in the antibacterial ability of tea over time. Correlation analysis indicated that the antibacterial ability against Micrococcus tetragenus and Escherichia coli was influenced by metabolites such as aspartic acid, threonine, serine, gamma-aminobutyric acid, ornithine, alanine, arginine, and EGCG. Overall, this study presents an approach for identifying key metabolites to monitor tea quality effectively with relatively limited data.


Asunto(s)
Alcaloides , Aminoácidos , Antibacterianos , Catequina , , Catequina/análogos & derivados , Catequina/farmacología , Catequina/química , Catequina/análisis , Té/química , Aminoácidos/análisis , Antibacterianos/farmacología , Antibacterianos/química , Alcaloides/farmacología , Alcaloides/análisis , Alcaloides/química , Almacenamiento de Alimentos/métodos , Escherichia coli/efectos de los fármacos , Camellia sinensis/química
3.
Nat Prod Res ; 38(11): 1864-1873, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38739563

RESUMEN

Phytochemical studies of the stems and leaves of Stephania dielsiana Y.C.Wu yielded two new aporphine alkaloids (1 and 5), along with six known alkaloids (2-4 and 6-8). Their structures were characterised based on analyses of spectroscopic data, including one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS). The cytotoxic activities of the isolated compounds against a small panel of tumour cell lines were assessed by MTS assay. Interestingly, compound 2 exhibited particularly strong cytotoxic activities against HepG2, MCF7 and OVCAR8 cancer cell lines, with IC50 values of 3.20 ± 0.18, 3.10 ± 0.06 and 3.40 ± 0.007 µM, respectively. Furthermore, molecular docking simulations were carried out to explore the interactions and binding mechanisms of the most active compound (compound 2) with proteins. Our results contribute to understanding the secondary metabolites produced by S. dielsiana and provide a scientific rationale for further investigations of cytotoxicity of this valuable medicinal plant.


Asunto(s)
Alcaloides , Antineoplásicos Fitogénicos , Aporfinas , Simulación del Acoplamiento Molecular , Hojas de la Planta , Tallos de la Planta , Stephania , Aporfinas/química , Aporfinas/farmacología , Humanos , Hojas de la Planta/química , Tallos de la Planta/química , Alcaloides/química , Alcaloides/farmacología , Stephania/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Estructura Molecular , Línea Celular Tumoral , Células Hep G2 , Células MCF-7 , Ensayos de Selección de Medicamentos Antitumorales , Espectroscopía de Resonancia Magnética , Plantas Medicinales/química
4.
Int J Mol Sci ; 25(9)2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38732250

RESUMEN

One previously undescribed alkaloid, named penifuranone A (1), and three known compounds (2-4) were isolated from the mangrove endophytic fungus Penicillium crustosum SCNU-F0006. The structure of the new alkaloid (1) was elucidated based on extensive spectroscopic data analysis and single-crystal X-ray diffraction analysis. Four natural isolates and one new synthetic derivative of penifuranone A, compound 1a, were screened for their antimicrobial, antioxidant, and anti-inflammatory activities. Bioassays revealed that penifuranone A (1) exhibited strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 42.2 µM. The docking study revealed that compound 1 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.


Asunto(s)
Alcaloides , Óxido Nítrico , Penicillium , Penicillium/química , Penicillium/metabolismo , Ratones , Animales , Alcaloides/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Células RAW 264.7 , Óxido Nítrico/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Óxido Nítrico Sintasa de Tipo II/metabolismo , Simulación del Acoplamiento Molecular , Lipopolisacáridos , Antioxidantes/farmacología , Antioxidantes/química , Estructura Molecular
5.
Molecules ; 29(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38731459

RESUMEN

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.


Asunto(s)
Alcaloides , Terpenos , Alcaloides/química , Alcaloides/farmacología , Terpenos/química , Terpenos/farmacología , Humanos , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Estructura Molecular
6.
Molecules ; 29(9)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38731603

RESUMEN

A new quinazolinone alkaloid named peniquinazolinone A (1), as well as eleven known compounds, 2-(2-hydroxy-3-phenylpropionamido)-N-methylbenzamide (2), viridicatin (3), viridicatol (4), (±)-cyclopeptin (5a/5b), dehydrocyclopeptin (6), cyclopenin (7), cyclopenol (8), methyl-indole-3-carboxylate (9), 2,5-dihydroxyphenyl acetate (10), methyl m-hydroxyphenylacetate (11), and conidiogenone B (12), were isolated from the endophytic Penicillium sp. HJT-A-6. The chemical structures of all the compounds were elucidated by comprehensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS. The absolute configuration at C-13 of peniquinazolinone A (1) was established by applying the modified Mosher's method. Compounds 2, 3, and 7 exhibited an optimal promoting effect on the seed germination of Rhodiola tibetica at a concentration of 0.01 mg/mL, while the optimal concentration for compounds 4 and 9 to promote Rhodiola tibetica seed germination was 0.001 mg/mL. Compound 12 showed optimal seed-germination-promoting activity at a concentration of 0.1 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compounds 2, 3, 4, 7, 9, and 12 could extend the seed germination period of Rhodiola tibetica up to the 11th day.


Asunto(s)
Alcaloides , Penicillium , Quinazolinonas , Rhodiola , Semillas , Penicillium/química , Quinazolinonas/química , Quinazolinonas/farmacología , Rhodiola/química , Rhodiola/microbiología , Alcaloides/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Germinación/efectos de los fármacos , Estructura Molecular , Endófitos/química
7.
Mar Drugs ; 22(4)2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38667758

RESUMEN

Nemertean worms contain toxins that are used to paralyze their prey and to deter potential predators. Hoplonemerteans often contain pyridyl alkaloids like anabaseine that act through nicotinic acetylcholine receptors and crustacean chemoreceptors. The chemical reactivity of anabaseine, the first nemertean alkaloid to be identified, has been exploited to make drug candidates selective for alpha7 subtype nAChRs. GTS-21, a drug candidate based on the anabaseine scaffold, has pro-cognitive and anti-inflammatory actions in animal models. The circumpolar chevron hoplonemertean Amphiporus angulatus contains a multitude of pyridyl compounds with neurotoxic, anti-feeding, and anti-fouling activities. Here, we report the isolation and structural identification of five new compounds, doubling the number of pyridyl alkaloids known to occur in this species. One compound is an isomer of the tobacco alkaloid anatabine, another is a unique dihydroisoquinoline, and three are analogs of the tetrapyridyl nemertelline. The structural characteristics of these ten compounds suggest several possible pathways for their biosynthesis.


Asunto(s)
Alcaloides , Isoquinolinas , Animales , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Isoquinolinas/farmacología , Isoquinolinas/química , Isoquinolinas/aislamiento & purificación , Invertebrados/química , Piridinas/farmacología , Piridinas/química , Piridinas/aislamiento & purificación , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/efectos de los fármacos , Estructura Molecular
8.
Mar Drugs ; 22(4)2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38667790

RESUMEN

In this study, Antarctic Latrunculia sponge-derived discorhabdin G was considered a hit for developing potential lead compounds acting as cholinesterase inhibitors. The hypothesis on the pharmacophore moiety suggested through molecular docking allowed us to simplify the structure of the metabolite. ADME prediction and drug-likeness consideration provided valuable support in selecting 5-methyl-2H-benzo[h]imidazo[1,5,4-de]quinoxalin-7(3H)-one as a candidate molecule. It was synthesized in a four-step sequence starting from 2,3-dichloronaphthalene-1,4-dione and evaluated as an inhibitor of electric eel acetylcholinesterase (eeAChE), human recombinant AChE (hAChE), and horse serum butyrylcholinesterase (BChE), together with other analogs obtained by the same synthesis. The candidate molecule showed a slightly lower inhibitory potential against eeAChE but better inhibitory activity against hAChE than discorhabdin G, with a higher selectivity for AChEs than for BChE. It acted as a reversible competitive inhibitor, as previously observed for the natural alkaloid. The findings from the in vitro assay were relatively consistent with the data available from the AutoDock Vina and Protein-Ligand ANTSystem (PLANTS) calculations.


Asunto(s)
Acetilcolinesterasa , Alcaloides , Butirilcolinesterasa , Inhibidores de la Colinesterasa , Electrophorus , Simulación del Acoplamiento Molecular , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Animales , Acetilcolinesterasa/metabolismo , Alcaloides/farmacología , Alcaloides/química , Butirilcolinesterasa/metabolismo , Humanos , Poríferos/química , Relación Estructura-Actividad , Caballos
9.
J Nat Prod ; 87(4): 1103-1115, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38600744

RESUMEN

Twelve new alkaloids, scolopenolines A-L (1-7, 9-11, 13, 14), along with six known analogues, were isolated from Scolopendra subspinipes mutilans, identified by analysis of spectroscopic data and quantum chemical and computational methods. Scolopenoline A (1), a unique guanidyl-containing C14 quinoline alkaloid, features a 6/6/5 ring backbone. Scolopenoline B (2) is a novel sulfonyl-containing heterodimer comprising quinoline and tyramine moieties. Scolopenoline G (7) presents a rare C12 quinoline skeleton with a 6/6/5 ring system. Alkaloids 1, 8, 10, and 15-18 display anti-inflammatory activity, while 10 and 16-18 also exhibit anti-renal-fibrosis activity. Drug affinity responsive target stability and RNA-interference assays show that Lamp2 might be a potentially important target protein of 16 for anti-renal-fibrosis activity.


Asunto(s)
Alcaloides , Animales Ponzoñosos , Quilópodos , Animales , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Estructura Molecular , Artrópodos/química , Fibrosis/tratamiento farmacológico , Riñón/efectos de los fármacos , Quinolinas/farmacología , Quinolinas/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Humanos
10.
Sci Rep ; 14(1): 9483, 2024 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664520

RESUMEN

The present study predicts the molecular targets and druglike properties of the phyto-compound piperine (PIP) by in silico studies including molecular docking simulation, druglikeness prediction and ADME analysis for prospective therapeutic benefits against diabetic complications. PIP was encapsulated in biodegradable polymer poly-lactide-co-glycolide (PLGA) to form nanopiperine (NPIP) and their physico-chemical properties were characterized by AFM and DLS. ∼ 30 nm sized NPIP showed 86.68% encapsulation efficiency and - 6 mV zeta potential, demonstrated great interactive stability and binding with CT-DNA displaying upsurge in molar ellipticity during CD spectroscopy. NPIP lowered glucose levels in peripheral circulation by > 65 mg/dL compared to disease model and improved glucose influx in alloxan-induced in vivo and in vitro diabetes models concerted with 3-folds decrease in ROS production, ROS-induced DNA damage and 27.24% decrease in nuclear condensation. The 25% increase in % cell viability and inhibition in chromosome aberration justified the initiation of p53 and PARP DNA repairing protein expression and maintenance of Hsp90. Thus, the experimental study corroborated well with in silico predictions of modulating the p53/PARP-1/Hsp90 axis, with predicted dock score value of - 8.72, - 8.57, - 8.76 kcal/mol respectively, validated docking-based preventive approaches for unravelling the intricacies of molecular signalling and nano-drug efficacy as therapeutics for diabetics.


Asunto(s)
Alcaloides , Benzodioxoles , Proteínas HSP90 de Choque Térmico , Hiperglucemia , Simulación del Acoplamiento Molecular , Piperidinas , Poli(ADP-Ribosa) Polimerasa-1 , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Alcamidas Poliinsaturadas , Proteína p53 Supresora de Tumor , Proteína p53 Supresora de Tumor/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Animales , Piperidinas/farmacología , Piperidinas/química , Benzodioxoles/farmacología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Alcaloides/farmacología , Alcaloides/química , Alcaloides/administración & dosificación , Alcamidas Poliinsaturadas/farmacología , Alcamidas Poliinsaturadas/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Aloxano , Ratas , Humanos , Masculino , Especies Reactivas de Oxígeno/metabolismo , Ratones , Nanopartículas/química , Daño del ADN/efectos de los fármacos
11.
Rapid Commun Mass Spectrom ; 38(13): e9760, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38682312

RESUMEN

RATIONALE: The chemical constituents of traditional Tibetan medicines (TTM) can be identified using high-performance liquid chromatography and high-resolution mass spectrometry (HPLC-MS/MS) technique. However, the HPLC-MS/MS technique requires the sample to be pretreated and then separated using the specific liquid chromatography method, which is time consuming. This study developed a ballpoint electrospray ionization (BPESI) technique for analyzing the chemical constituents of Sbyor-bzo-ghi-wang. This technique is a simple and inexpensive method for the rapid identification of the chemical constituents of TTMs. METHODS: After the important parameters of the homemade BPESI device were optimized, the chemical constituents of Sbyor-bzo-ghi-wang were quickly identified without sample pretreatment. The raw data were converted to mzML file using MSConvert and then identified using SIRIUS 5 software. RESULTS: The results showed that 30 compounds were identified from Sbyor-bzo-ghi-wang, namely eight bile acids, six flavonoids, four alkaloids, three amino acids, and nine others. Compared to the ultra-high-performance liquid chromatography-Q/Orbitrap and high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS) technique, the BPESI technique identified almost similar types of compounds and also a comparable number of compounds. CONCLUSIONS: Compared with the traditional HPLC-MS/MS methods, the BPESI technique does not require complex sample pretreatment and subsequent chromatographic separation steps; also it consumes a small quantity of samples. Therefore, BPESI can be used for the qualitative analysis of the chemical constituents of Sbyor-bzo-ghi-wang.


Asunto(s)
Medicina Tradicional Tibetana , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Ionización de Electrospray/métodos , Cromatografía Líquida de Alta Presión/métodos , Flavonoides/análisis , Flavonoides/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Alcaloides/análisis , Alcaloides/química , Ácidos y Sales Biliares/análisis , Ácidos y Sales Biliares/química , Aminoácidos/análisis , Aminoácidos/química , Extractos Vegetales/química
12.
Molecules ; 29(8)2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38675582

RESUMEN

Piper betle leaf powder is increasingly utilised as a health supplement. In this study, P. betle leaves were subjected to four different drying methods: convective air-drying, oven-drying, sun-drying, and no drying, with fresh leaves as control. Their antioxidant properties were then evaluated using colourimetric assays and GC-MS. Results showed that the sun-dried leaves had the highest (p < 0.05) total antioxidant capacity (66.23 ± 0.10 mg AAE/g), total polyphenol content (133.93 ± 3.76 mg GAE/g), total flavonoid content (81.25 ± 3.26 mg CE/g) and DPPH radical scavenging activity (56.48 ± 0.11%), and the lowest alkaloid content (45.684 ± 0.265 mg/gm). GC-MS analysis revealed that major constituents of aqueous extracts of fresh and sun-dried P. betle leaves were hydrazine 1,2-dimethyl-; ethyl aminomethylformimidate; glycerin; propanoic acid, 2-hydroxy-, methyl ester, (+/-)-; and 1,2-Cyclopentanedione. In conclusion, sun-dried leaves exhibited overall better antioxidant properties, and their aqueous extracts contained biologically active phytoconstituents that have uses in various fields.


Asunto(s)
Antioxidantes , Desecación , Piper betle , Extractos Vegetales , Hojas de la Planta , Hojas de la Planta/química , Antioxidantes/química , Antioxidantes/farmacología , Piper betle/química , Extractos Vegetales/química , Desecación/métodos , Flavonoides/química , Flavonoides/análisis , Polifenoles/química , Polifenoles/análisis , Cromatografía de Gases y Espectrometría de Masas , Alcaloides/química , Alcaloides/análisis
13.
Molecules ; 29(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38675664

RESUMEN

The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemotherapy from LST-4 NPs and the synergistic amplification of oxidative damage, through increasing the reactive oxygen species (ROS) by photodynamic therapy (PDT), causing an GSH decrease via LST-4 mediation to effectively kill tumor cells. Therefore, multifunctional LST-4@ZnPc NPs are a promising method for killing cancer cells, which also provides a new paradigm for using natural products to kill tumors.


Asunto(s)
Alcaloides , Glutatión , Indoles , Isoindoles , Matrinas , Quinolizinas , Especies Reactivas de Oxígeno , Alcaloides/química , Alcaloides/farmacología , Especies Reactivas de Oxígeno/metabolismo , Quinolizinas/química , Quinolizinas/farmacología , Glutatión/metabolismo , Humanos , Animales , Indoles/química , Indoles/farmacología , Ratones , Línea Celular Tumoral , Compuestos de Zinc/química , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Fotoquimioterapia/métodos , Proteolisis , Nanopartículas/química
14.
J Agric Food Chem ; 72(14): 8225-8236, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38557068

RESUMEN

As a continuous flow investigation of novel pesticides from natural quinolizidine alkaloids, the chemical compositions of the seeds of Sophora alopecuroides were thoroughly researched. Fifteen new aloperine-type alkaloids (1-15) as well as six known aloperine-type alkaloids (16-21) were obtained from the extract of S. alopecuroides. The structures of 1-21 were confirmed via HRESIMS, NMR, UV, IR, ECD calculations, and X-ray diffraction. The antiviral activities of 1-21 against tobacco mosaic virus (TMV) were detected following the improved method of half-leaf. Compared with ningnanmycin (protective: 69.7% and curative: 64.3%), 15 exhibited excellent protective (71.7%) and curative (64.6%) activities against TMV. Further biological studies illustrated that 15 significantly inhibited the transcription of the TMV-CP gene and increased the activities of polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD), and phenylalanine ammonia-lyase (PAL). The antifungal activities of 1-21 against Phytophythora capsica, Botrytis cinerea, Alternaria alternata, and Gibberella zeae were screened according to a mycelial inhibition test. Compound 13 displayed excellent antifungal activity against B. cinerea (EC50: 7.38 µg/mL). Moreover, in vitro antifungal mechanism studies displayed that 13 causes accumulation of reactive oxygen species and finally leads to mycelia cell membrane damage and cell death in vitro.


Asunto(s)
Alcaloides , Quinolizidinas , Sophora , Virus del Mosaico del Tabaco , Antifúngicos , Sophora/química , Alcaloides/química , Antivirales/farmacología , Antivirales/química , Semillas/química
15.
Antimicrob Agents Chemother ; 68(5): e0161223, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38602413

RESUMEN

Mycetoma is a devastating neglected tropical infection of the subcutaneous tissues. It is caused by fungal and bacterial pathogens recognized as eumycetoma and actinomycetoma, respectively. Mycetoma treatment involves diagnosing the causative microorganism as a prerequisite to prescribing a proper medication. Current therapy of fungal eumycetoma causative agents, such as Madurella mycetomatis, consists of long-term antifungal medication with itraconazole followed by surgery, yet with usually unsatisfactory clinical outcomes. Actinomycetoma, on the contrary, usually responds to treatment with co-trimoxazole and amikacin. Therefore, there is a pressing need to discover novel broad-spectrum antimicrobial agents to circumvent the time-consuming and costly diagnosis. Using the resazurin assay, a series of 23 naphthylisoquinoline (NIQ) alkaloids and related naphthoquinones were subjected to in vitro screening against two fungal strains of M. mycetomatis and three bacterial strains of Actinomadura madurae and A. syzygii. Seven NIQs, mostly dimers, showed promising in vitro activities against at least one strain of the mycetoma-causative pathogens, while the naphthoquinones did not show any activity. A synthetic NIQ dimer, 8,8'''-O,O-dimethylmichellamine A (18), inhibited all tested fungal and bacterial strains (IC50 = 2.81-12.07 µg/mL). One of the dimeric NIQs, michellamine B (14), inhibited a strain of M. mycetomatis and significantly enhanced the survival rate of Galleria mellonella larvae infected with M. mycetomatis at concentrations of 1 and 4 µg/mL, without being toxic to the uninfected larvae. As a result, broad-spectrum dimeric NIQs like 14 and 18 with antimicrobial activity are considered hit compounds that could be worth further optimization to develop novel lead antimycetomal agents.


Asunto(s)
Alcaloides , Antifúngicos , Madurella , Pruebas de Sensibilidad Microbiana , Micetoma , Micetoma/tratamiento farmacológico , Micetoma/microbiología , Antifúngicos/farmacología , Animales , Alcaloides/farmacología , Alcaloides/química , Madurella/efectos de los fármacos , Isoquinolinas/farmacología , Actinomadura/efectos de los fármacos , Naftoquinonas/farmacología , Larva/microbiología , Larva/efectos de los fármacos , Mariposas Nocturnas/microbiología
16.
Phytochemistry ; 222: 114093, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38615927

RESUMEN

Nine 3-arylisoquinoline alkaloids including five undescribed ones, hypectumines A-E (1-5), were isolated from the whole herb of Hypecoum erectum L. with the guidance of 1H-NMR. Their structures were established by a combination of 1D, 2D NMR, and HRESIMS spectrometry. Among them, hypectumines A and B possessed rare urea moieties while hypectumines C and D were characterized by 3-(methylamino)propanoic acid scaffolds. Biological assay demonstrated that alkaloids hypectumine B and 2,3-dimethoxy-N-formylcorydamine had anti-inflammatory effects by inhibiting NO production on LPS-induced RAW264.7 cells with IC50 values of 24.4 and 44.2 µM, respectively. Furthermore, hypectumine B could reduce the expression of pro-inflammatory cytokines TNF-α and IL-6, suggesting it might be a potential candidate for treating inflammatory disease.


Asunto(s)
Alcaloides , Lipopolisacáridos , Animales , Ratones , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Células RAW 264.7 , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Estructura Molecular , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Isoquinolinas/farmacología , Isoquinolinas/química , Isoquinolinas/aislamiento & purificación , Óxido Nítrico/biosíntesis , Óxido Nítrico/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo , Relación Estructura-Actividad , Interleucina-6/metabolismo , Relación Dosis-Respuesta a Droga , Espectroscopía de Protones por Resonancia Magnética
17.
J Org Chem ; 89(9): 5977-5987, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38557022

RESUMEN

Mellpaladines A-C (1-3) and dopargimine (4) are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (5), three additional mellpaladines D-F (6-8), and serotodopalgimine (9), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (10). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound 4 and its congeners dopargine (11), nordopargimine (15), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine (16) were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of 1-4 using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for in vivo behavioral toxicity. Interestingly, these alkaloids also emerged during a screen of our marine natural product library aimed at identifying antiviral activities against dengue virus, SARS-CoV-2, and vesicular stomatitis Indiana virus (VSV) pseudotyped with Ebola virus glycoprotein (VSV-ZGP).


Asunto(s)
Alcaloides , Dopamina , Urocordados , Animales , Alcaloides/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Alcaloides/síntesis química , Urocordados/química , Ratones , Dopamina/química , Dopamina/farmacología , Estructura Molecular , Guanidina/química , Guanidina/farmacología , Antivirales/farmacología , Antivirales/química , Antivirales/aislamiento & purificación , Antivirales/síntesis química , Guanidinas/química , Guanidinas/farmacología , Guanidinas/aislamiento & purificación , SARS-CoV-2/efectos de los fármacos , Humanos
18.
Talanta ; 274: 125923, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38569366

RESUMEN

Mitragyna speciosa, more commonly known as kratom, has emerged as an alternative to treat chronic pain and addiction. However, the alkaloid components of kratom, which are the major contributors to kratom's pharmaceutical properties, have not yet been fully investigated. In this study, matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry was used to map the biodistribution of three alkaloids (corynantheidine, mitragynine, and speciogynine) in rat brain tissues. The alkaloids produced three main ion types during MALDI analysis: [M + H]+, [M - H]+, and [M - 3H]+. Contrary to previous reports suggesting that the [M - H]+ and [M - 3H]+ ion types form during laser ablation, these ion types can also be produced during the MALDI matrix application process. Several strategies are proposed to accurately map the biodistribution of the alkaloids. Due to differences in the relative abundances of the ions in different biological regions of the tissue, differences in ionization efficiencies of the ions, and potential overlap of the [M - H]+ and [M - 3H]+ ion types with endogenous metabolites of the same empirical formula, a matrix that mainly produces the [M + H]+ ion type is optimal for accurate mapping of the alkaloids. Alternatively, the most abundant ion type can be mapped or the intensities of all ion types can be summed together to generate a composite image. The accuracy of each of these approaches is explored and validated.


Asunto(s)
Alcaloides , Encéfalo , Mitragyna , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Animales , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Mitragyna/química , Ratas , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Alcaloides/farmacocinética , Alcaloides/análisis , Alcaloides/química , Masculino , Iones/química , Distribución Tisular , Ratas Sprague-Dawley
19.
J Nat Prod ; 87(4): 1187-1196, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38632902

RESUMEN

Psammaplins are sulfur containing bromotyrosine alkaloids that have shown antitumor activity through the inhibition of class I histone deacetylases (HDACs). The cytotoxic properties of psammaplin A (1), the parent compound, are related to peroxisome proliferator-activated receptor γ (PPARγ) activation, but the mechanism of action of its analogs psammaplin K (2) and bisaprasin (3) has not been elucidated. In this study, the protective effects against oxidative stress of compounds 1-3, isolated from the sponge Aplysinella rhax, were evaluated in SH-SY5Y cells. The compounds improved cell survival, recovered glutathione (GSH) content, and reduced reactive oxygen species (ROS) release at nanomolar concentrations. Psammaplins restored mitochondrial membrane potential by blocking mitochondrial permeability transition pore opening and reducing cyclophilin D expression. This effect was mediated by the capacity of 1-3 to activate PPARγ, enhancing gene expression of the antioxidant enzymes catalase, nuclear factor E2-related factor 2 (Nrf2), and glutathione peroxidase. Finally, HDAC3 activity was reduced by 1-3 under oxidative stress conditions. This work is the first description of the neuroprotective activity of 1 at low concentrations and the mechanism of action of 2 and 3. Moreover, it links for the first time the previously described effects of 1 in HDAC3 and PPARγ signaling, opening a new research field for the therapeutic potential of this compound family.


Asunto(s)
Disulfuros , Estrés Oxidativo , PPAR gamma , Tirosina/análogos & derivados , PPAR gamma/metabolismo , Estrés Oxidativo/efectos de los fármacos , Humanos , Animales , Estructura Molecular , Especies Reactivas de Oxígeno/metabolismo , Neuronas/efectos de los fármacos , Histona Desacetilasas/metabolismo , Histona Desacetilasas/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Poríferos/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Glutatión/metabolismo , Alcaloides/farmacología , Alcaloides/química , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/efectos de los fármacos , Proteínas de Transporte de Membrana Mitocondrial/metabolismo
20.
J Ethnopharmacol ; 330: 118218, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38677570

RESUMEN

ETHNOPHARMACOLOGY RELEVANCE: Zanthoxylum bungeanum Maxim. (Z. bungeanum), a member of the Rutaceae family, has a rich history of traditional use in Asia for treating arthritis and toothache conditions. As characteristic chemical components, numerous kinds of alkaloids have been extracted from plants and their diverse biological activities have been reported. However, research on the isoquinoline alkaloid, a specific type of alkaloids, in Z. bungeanum was scarce. AIM OF THE STUDY: The study aimed to isolate a novel isoquinoline alkaloid from Z. bungeanum and explore its pharmacological activity in vitro and analgesic activity in vivo. MATERIALS AND METHODS: Isoquinoline alkaloid isolation and identification from Z. bungeanum were conducted using chromatographic and spectroscopic methods. The whole-cell patch-clamp technique was applied to assess its impact on neuronal excitability, and endogenous voltage-gated potassium (Kv) and sodium (Nav) currents in acutely isolated mouse small-diameter dorsal root ganglion (DRG) neurons. Its inhibitory impacts on channels were further validated with HEK293 cells stably expressing Nav1.7 and Nav1.8, and Chinese hamster ovary (CHO) cells transiently expressing Kv2.1. The formalin inflammatory pain model was utilized to evaluate the potential analgesic activity in vivo. RESULTS: A novel isoquinoline alkaloid named HJ-69 (N-13-(3-methoxyprop-1-yl)rutaecarpine) was isolated and identified from Z. bungeanum for the first time. HJ-69 significantly suppressed the firing frequency and amplitudes of action potentials in DRG neurons. Consistently, it state-dependently inhibited endogenous Nav currents of DRG neurons, with half maximal inhibitory concentration (IC50) values of 13.06 ± 2.06 µM and 30.19 ± 2.07 µM for the inactivated and resting states, respectively. HJ-69 significantly suppressed potassium currents in DRG neurons, which notably inhibited the delayed rectifier potassium (IK) currents (IC50 = 6.95 ± 1.29 µM) and slightly affected the transient outward potassium (IA) currents (IC50 = 523.50 ± 39.16 µM). Furtherly, HJ-69 exhibited similar potencies on heterologously expressed Nav1.7, Nav1.8, and Kv2.1 channels, which correspondingly represent the main components in neurons. Notably, intraperitoneal administration of 30 mg/kg and 100 mg/kg HJ-69 significantly alleviated pain behaviors in the mouse inflammatory pain model induced by formalin. CONCLUSION: The study concluded that HJ-69 is a novel and active isoquinoline alkaloid, and the inhibition of Nav and Kv channels contributes to its analgesic activity. HJ-69 may be a promising prototype for future analgesic drug discovery based on the isoquinoline alkaloid.


Asunto(s)
Analgésicos , Ganglios Espinales , Dolor , Zanthoxylum , Animales , Zanthoxylum/química , Humanos , Células HEK293 , Analgésicos/farmacología , Analgésicos/química , Analgésicos/aislamiento & purificación , Analgésicos/uso terapéutico , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Ratones , Masculino , Dolor/tratamiento farmacológico , Isoquinolinas/farmacología , Isoquinolinas/aislamiento & purificación , Isoquinolinas/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Alcaloides/química , Alcaloides/uso terapéutico , Bloqueadores de los Canales de Potasio/farmacología , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Inflamación/tratamiento farmacológico , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacología , Bloqueadores del Canal de Sodio Activado por Voltaje/aislamiento & purificación , Canales de Potasio con Entrada de Voltaje/metabolismo , Canales de Potasio con Entrada de Voltaje/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/química , Ratones Endogámicos C57BL , Cricetulus
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