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1.
Phytochemistry ; 217: 113929, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37984589

RESUMO

Eleven previously undescribed Amaryllidaceae alkaloids, crinalatifolines A-K (1-11), and two first naturally occurring alkaloids, dihydroambelline (12) and N-demethyldihydrogalanthamine (13), were isolated from the bulbs of Crinum latifolium L. Additionally, thirty-seven known alkaloids and one alkaloid artifact were also isolated from this plant species. Their structures and absolute configurations were elucidated using extensive spectroscopic techniques, including IR, NMR, MS, and ECD. Evaluations of the cholinesterase inhibitory activities of most of these compounds were conducted. Among the tested compounds, ungeremine exhibited the highest potency against acetylcholinesterase and butyrylcholinesterase, with the IC50 values of 0.10 and 1.21 µM, respectively. These values were 9.4- and 2.4-fold more potent than the reference drug galanthamine.


Assuntos
Alcaloides , Alcaloides de Amaryllidaceae , Crinum , Alcaloides de Amaryllidaceae/farmacologia , Alcaloides de Amaryllidaceae/química , Crinum/química , Butirilcolinesterase , Acetilcolinesterase , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Alcaloides/farmacologia , Alcaloides/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química
2.
Phytochemistry ; 216: 113883, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37820888

RESUMO

Crinum x powellii 'Album' belongs to the Amaryllidaceae medicinal plant family that produces a range of structurally diverse alkaloids with potential therapeutic properties. The optimal conditions for in vitro tissue growth, morphogenesis, and alkaloid biosynthesis remain unclear. Auxin and light play critical roles in regulating plant growth, development, and alkaloid biosynthesis in several Amaryllidaceae plants. Here, we have succeeded in showing, for the first time, that the combination of auxin and light significantly influence C. x powellii "Album" in vitro tissue growth, survival, and morphogenesis compared to individual treatments. Furthermore, this combination also upregulates the expression of alkaloid biosynthetic genes and led to an increase in the content of certain alkaloids, suggesting a positive impact on the defense and therapeutic potential of the calli. Our findings provide insights into the regulation of genes involved in alkaloid biosynthesis in C. x powellii "Album" callus and underline the potential of auxin and light as tools for enhancing their production in plants. This study provides a foundation for further exploration of C. x powellii "Album" calli as a sustainable source of bioactive alkaloids for pharmaceutical and agricultural applications. Furthermore, this study paves the way to the discovery of the biosynthetic pathway of specialized metabolites from C. x powellii "Album", such as cherylline and lycorine.


Assuntos
Alcaloides , Alcaloides de Amaryllidaceae , Crinum , Crinum/metabolismo , Ácidos Indolacéticos , Alcaloides de Amaryllidaceae/farmacologia , Alcaloides/metabolismo , Extratos Vegetais , Morfogênese
3.
Appl Microbiol Biotechnol ; 107(7-8): 2155-2167, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36922438

RESUMO

Genus Crinum L. is a member of the Amaryllidaceae family having beautiful, huge, ornamental plants with umbels of lily-like blooms that are found in tropical and subtropical climates all over the world. For thousands of years, Crinum has been used as a traditional medicine to treat illnesses and disorders. Numerous distinct alkaloids of the Amaryllidaceae group, whose most well-known properties include analgesic, anticholinergic, antitumor, and antiviral, have recently been discovered by phytochemical analyses. However, because of decades of overexploitation for their economically significant bioactive ingredients and poor seed viability and germination rates, these plants are now threatened in their native environments. Because of these factors, researchers are investigating micropropagation techniques to optimize phytochemicals in vitro. This review's objective is to offer details on the distribution, phytochemistry, micropropagation, in vitro galanthamine synthesis, and pharmacology which will help to design biotechnological techniques for the preservation, widespread multiplication, and required secondary metabolite production from Crinum spp. KEY POINTS: • Botanical description and phytochemical profile of Crinum spp. • In vitro micropropagation method of Crinum sp. • Bioactive compound galanthamine isolation techniques and its pharmacological properties.


Assuntos
Alcaloides , Crinum , Crinum/química , Extratos Vegetais/farmacologia , Galantamina , Alcaloides/química , Compostos Fitoquímicos
4.
Phytochemistry ; 205: 113473, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36244402

RESUMO

Seven previously undescribed alkaloids, crinamabilines A-G, two non-alkaloidal compounds, crinamabidiene and 6-phenylpiperonyl alcohol, two first naturally occurring alkaloids, 3-epibuphanisine and (+)-1ß,2ß-epoxy-epicrinine, together with nineteen known alkaloids, were isolated from the bulbs of Crinum × amabile Donn ex Ker Gawl. Their structures and absolute configurations were elucidated by NMR, MS and ECD spectroscopic techniques. Ungeremine displayed the most potent inhibitory activity against acetylcholinesterase (IC50 0.21 µM), which was about 6-fold more active than the reference drug, galanthamine (IC50 1.23 µM). Ungeremine also exhibited the strongest inhibitory activity against butyrylcholinesterase (IC50 3.57 µM), which was comparable to galanthamine (IC50 3.11 µM). The molecular docking studies were performed and were well in agreement with the experimental results.


Assuntos
Crinum , Butirilcolinesterase , Acetilcolinesterase , Simulação de Acoplamento Molecular
5.
Plant Biol (Stuttg) ; 25(1): 142-151, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36040406

RESUMO

Crinum malabaricum Lekhak & Yadav is a recently discovered and critically endangered aquatic bulbous plant of the family Amaryllidaceae. It gained attention as a wild source of the acetylcholinesterase inhibiting alkaloid 'galanthamine' used to treat Alzheimer and Parkinson diseases. The bulbs of this plant contain the highest amount of galanthamine among Crinum species. In vitro regeneration systems were developed to produce quality uniform plantlets of C. malabaricum. Bright field light microscopy was used to analyse micro-morpho-anatomical developments taking place in the leaves and roots during in vitro, ex vitro and in vivo transitions of plantlets. Leaves and roots of plants raised in vitro possessed a higher degree of microscopic structural anomalies, such as underdeveloped epicuticular wax deposition, immature and non-functional stomata, more aquiferous parenchyma with a reduced lumen. Roots developed in vitro were characterized by extremely large, uneven cortical cells and reduced intercellular spaces. The vascular tissues were under-developed and only primary vascular tissues were observed. As a result of ex vitro acclimation, there was a significant acceleration in the improvement of tissue systems in leaves and roots. Such plantlets can tolerate elevated temperatures and light under in vivo conditions. Thus, the microscopic evaluation of the structural trajectory in different stages of plantlet development provides an understanding of the acclimation process and structural adaptations, which could help enhance survival of in vitro raised plantlets under ex vitro and in vivo conditions.


Assuntos
Alcaloides , Amaryllidaceae , Crinum , Plantas Medicinais , Crinum/química , Acetilcolinesterase
6.
Molecules ; 27(14)2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35889346

RESUMO

Amaryllidaceae is a significant source of bioactive phytochemicals with a strong propensity to develop new drugs. The genera Allium, Tulbaghia, Cyrtanthus and Crinum biosynthesize novel alkaloids and other phytochemicals with traditional and pharmacological uses. Amaryllidaceae biomolecules exhibit multiple pharmacological activities such as antioxidant, antimicrobial, and immunomodulatory effects. Traditionally, natural products from Amaryllidaceae are utilized to treat non-communicable and infectious human diseases. Galanthamine, a drug from this family, is clinically relevant in treating the neurocognitive disorder, Alzheimer's disease, which underscores the importance of the Amaryllidaceae alkaloids. Although Amaryllidaceae provide a plethora of biologically active compounds, there is tardiness in their development into clinically pliable medicines. Other genera, including Cyrtanthus and Tulbaghia, have received little attention as potential sources of promising drug candidates. Given the reciprocal relationship of the increasing burden of human diseases and limited availability of medicinal therapies, more rapid drug discovery and development are desirable. To expedite clinically relevant drug development, we present here evidence on bioactive compounds from the genera Allium, Tulgbaghia, Cyrtanthus and Crinum and describe their traditional and pharmacological applications.


Assuntos
Allium , Alcaloides de Amaryllidaceae , Amaryllidaceae , Crinum , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacologia , Crinum/química , Humanos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia
7.
Molecules ; 27(9)2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35566325

RESUMO

Candida species are the main fungal agents causing infectious conditions in hospital patients. The development of new drugs with antifungal potential, increased efficacy, and reduced toxicity is essential to face the challenge of fungal resistance to standard treatments. The aim of this study is to evaluate the in vitro antifungal effects of two crude extracts of Crinum americanum L., a rich alkaloid fraction and lycorine alkaloid, on the Candida species. As such, we used a disk diffusion susceptibility test, determined the minimum inhibitory concentration (MIC), and characterized the components of the extracts using Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (ESI FT-ICR MS). The extracts were found to have antifungal activity against various Candida species. The chemical characterization of the extracts indicated the presence of alkaloids such as lycorine and crinine. The Amaryllidaceae family has a promising antifungal potential. Furthermore, it was found that the alkaloid lycorine directly contributes to the effects that were observed for the extracts and fraction of C. americanum.


Assuntos
Alcaloides , Alcaloides de Amaryllidaceae , Amaryllidaceae , Crinum , Alcaloides/química , Alcaloides/farmacologia , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Candida , Crinum/química , Humanos , Fenantridinas , Extratos Vegetais/química , Extratos Vegetais/farmacologia
8.
J Ethnopharmacol ; 296: 115359, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35605920

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Locally, among the Yoruba speaking people of South Western, Nigeria, the bulb of Crinum jagus (CJ), known as "ogede odo" is used to treat malaria and as an anthelmintic among other uses. AIMS OF THIS STUDY: Study aimed at identifying the purified active fractions and constituents of this fraction in an antiplasmodial activity-guided process. MATERIALS AND METHODS: Antiplasmodial activity-guided fractionation of the bulb and leaf extracts of CJ was investigated against chloroquine-sensitive (NK 65) Plasmodium berghei using 4-day suppressive and prophylactic methods. Molluscicidal activity of the extracts was assayed on adult Biomphalaria glabrata molluscs following WHO test protocols. Fractionation and purification of the active bulb extract was achieved using various chromatographic and spectroscopic techniques to isolate its constituents. Isolated compounds were identified using different spectroscopic methods. RESULTS AND DISCUSSION: Both extracts had oral median lethal dose (LD50) greater than 5000 mg/kg body weight (b.wt.). The leaf extract had 40% lethality on molluscs while the bulb extract was inactive. The chemosuppressive and prophylactic antimalarial effects of the bulb extract were 76.55 ± 2.76% and 90.49 ± 2.70% (p<0.05) respectively at 1000 mg/kg b. wt. while the reference drugs; chloroquine and pyrimethamine, had 80.26 ± 3.09% and 50.39 ± 6.80% chemosuppressive effects, respectively. Lycorine (1) and crinamine (2) were isolated from the alkaloidal fraction with 71.36 ± 12.54% antiplasmodial activity. CONCLUSION: The leaf and bulb extracts of Crinum jagus displayed low molluscicidal and moderate antimalarial activities. Lycorine and crinamine were identified from the antiplasmodial alkaloidal active fraction of the bulb.


Assuntos
Alcaloides , Antimaláricos , Crinum , Alcaloides/farmacologia , Antimaláricos/química , Antimaláricos/toxicidade , Cloroquina/farmacologia , Crinum/química , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plasmodium berghei
9.
BMC Complement Med Ther ; 22(1): 139, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35585532

RESUMO

BACKGROUND: Crinum latifolium L. (Amaryllidaceae) has been used in Southeast Asian traditional medicine to alleviate the symptoms of benign prostatic hyperplasia (BPH). The pathological mechanism of BPH is associated with the induction of prostate stromal cell proliferation through transforming growth factor-beta (TGF-ß). Standardization as well as investigation of the potential anti-BPH activity of C. latifolium extract could benefit the further development of BPH-related analyses and provide evidence to support the application of this extract for BPH treatment. This study aimed to standardize and investigate the antiproliferative activity of the ethanolic extract of C. latifolium leaves. The major alkaloids isolated from C. latifolium were also explored for their potential use as bioactive markers. METHODS: Two major alkaloids were isolated from the ethanolic extract of C. latifolium leaves by chromatographic techniques, identified by NMR and MS, and quantified by a validated UHPLC method. Their antiproliferative activity was studied in human prostate stromal cells (WPMY-1) induced by TGF-ß. The synergistic effect of combining the two major isolated alkaloids was analyzed by the zero interaction potency (ZIP) model. RESULTS: Two alkaloids, lycorine (1) and 6α-hydroxybuphanidrine (2), were isolated from the ethanolic leaf extract of C. latifolium. A UHPLC method for the quantification of (1) and (2) was developed and validated in terms of linearity, precision, and accuracy. The C. latifolium leaf extract contained 0.279 ± 0.003% (1) and 0.232 ± 0.004% (2). The crude extract was more potent than either (1) and (2) alone against TGF-ß-treated WPMY-1 cell proliferation. The drug combination study revealed that the greatest synergistic effect of (1) and (2) was achieved at a 1:1 ratio. CONCLUSIONS: The results of this study support the anti-BPH activity of C. latifolium in traditional medicine and suggest that these the two isolated alkaloids may promote the efficacy of the C. latifolium extract. Additionally, major alkaloids (1) and (2) can be used as bioactive markers for the standardization of C. latifolium extracts.


Assuntos
Alcaloides , Crinum , Hiperplasia Prostática , Alcaloides/farmacologia , Crinum/química , Humanos , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Próstata/patologia , Hiperplasia Prostática/tratamento farmacológico , Padrões de Referência , Células Estromais/patologia , Fator de Crescimento Transformador beta
10.
Environ Sci Pollut Res Int ; 29(19): 29130-29140, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34997511

RESUMO

Obesity is a multifaceted disease encompassing deposition of an unnecessary amount of fat which upsurges the possibility of other complications, viz., hypertension and certain type of cancers. Although obesity results from combination of genetic factors, improper diet and inadequate physical exercise also play a major role in its onset. The present study aims at exploring the anti-obesity activity of Crinum latifolia leaf extract in obese rats. The leaves were extracted using hydroalcoholic extraction which was later diluted with water and given to obese rats. The dosing was started from the 4th week (by oral administration of extract of Crinum latifolia (100 mg/kg and 200 mg/kg) and combination of Crinum latifolia leaf extract 200 mg/kg and orlistat 30 mg/kg) till the 10th week. Various angiogenic, antioxidant, biochemical, and inflammatory biomarkers were assessed at the end of the study. The obese symptoms were progressively reduced in treatment groups when compared to disease control groups. The angiogenic parameters and inflammatory parameters were consequently reduced in treatment groups. The oxidative parameters superoxide dismutase (SOD) and catalase were gradually increased, while levels of TBARS were reduced in treatment groups showing antioxidant nature of leaf hydroalcoholic extract. The Crinum latifolia leaf extract possesses anti-obesity properties and therefore can be used as a therapeutic option in the management of obesity.


Assuntos
Crinum , Animais , Antioxidantes/farmacologia , Crinum/química , Obesidade , Estresse Oxidativo , Extratos Vegetais/química , Ratos
11.
Planta Med ; 88(11): 913-920, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474490

RESUMO

Three new flavanols, (2R,3S)-7-methoxy-flavan-3-ol (1: ), (2R,3S)-7-hydroxy-flavan-3-ol (2: ), and (2R,3S)-2'-hydroxy-7-methoxy-flavan-3-ol (3: ), together with two known flavans (4: and 5: ), were isolated from the chloroform extract of Crinum asiaticum. Their structures were elucidated by various spectroscopic methods, including 1D and 2D NMR, HR-ESI-MS, and CD data. The isolated compounds 1: and 3: -5: showed inhibitory activity toward LPS-induced nitric oxide (NO) production. Further investigation of the NF-κB pathway mechanisms indicated that 1: and 3: -5: inhibited the LPS-induced IL-6 production and p65 subunit phosphorylation of NF-κB in RAW264.7 cells, with an effective dose of 10 µM.


Assuntos
Crinum , Flavonoides/química , NF-kappa B , Animais , Crinum/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Polifenóis , Células RAW 264.7 , Transdução de Sinais
12.
Biomolecules ; 11(9)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34572511

RESUMO

Crinum biflorum Rottb. (syn. Crinum distichum) is an Amaryllidaceae plant used in African traditional medicine but very few studies have been performed on this species from a chemical and applicative point of view. Bulbs of C. biflorum, collected in Senegal, were extracted with ethanol by Soxhlet and the corresponding organic extract was purified using chromatographic methods. The pure compounds were chemically characterized by spectroscopic techniques (1D and 2D 1H and 13C NMR, HR MS and ECD) and X-ray analysis. Four homoisoflavonoids (1-4) and one alkylamide (5) were isolated and characterized as 5,6,7-trimethoxy-3-(4-hydroxybenzyl)chroman-4-one (1), as 3-hydroxy-5,6,7-trimethoxy-3-(4-hydroxybenzyl)chroman-4-one (2), as 3-hydroxy-5,6,7-trimethoxy-3-(4-methoxybenzyl)chroman-4-one (3) and as 5,6,7-trimethoxy-3-(4-methoxybenzyl)chroman-4-one (4), and the alkylamide as (E)-N-(4-hydroxyphenethyl)-3-(4-hydroxyphenyl)acrylamide (5), commonly named N-p-coumaroyltyramine. The relative configuration of compound 1 was verified thanks to the X-ray analysis which also allowed us to confirm its racemic nature. The absolute configurations of compounds 2 and 3 were assigned by comparing their ECD spectra with those previously reported for urgineanins A and B. Flavanoids 1, 3 and 4 showed promising anticancer properties being cytotoxic at low micromolar concentrations towards HeLa and A431 human cancer cell lines. The N-p-coumaroyltyramine (5) was selectively toxic to A431 and HeLa cancer cells while it protected immortalized HaCaT cells against oxidative stress induced by hydrogen peroxide. Compounds 1-4 also inhibited acetylcholinesterase activity with compound 3 being the most potent. The anti-amylase and the strong anti-glucosidase activity of compound 5 were confirmed. Our results show that C. biflorum produces compounds of therapeutic interest with anti-diabetic, anti-tumoral and anti-acetylcholinesterase properties.


Assuntos
Amaryllidaceae/química , Ácidos Cumáricos/isolamento & purificação , Crinum/química , Flavonoides/isolamento & purificação , Acetilcolinesterase/metabolismo , Antivirais/farmacologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Ácidos Cumáricos/química , Flavonoides/química , Fluoresceínas/metabolismo , HIV-1/efeitos dos fármacos , Células HaCaT , Células HeLa , Humanos , Hipoglicemiantes/farmacologia , Metaboloma , Conformação Molecular , Senegal , alfa-Amilases/metabolismo
13.
Nat Prod Res ; 35(19): 3220-3225, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31762341

RESUMO

A new alkaloid, amabiloid A (1) was isolated from Crinum amabile along with eleven known compounds. Their structures were determined by 1D and 2D NMR spectroscopic data. In addition, the acetyl- and butyrylcholinesterase inhibitory activities of the isolated compounds were evaluated.


Assuntos
Alcaloides de Amaryllidaceae , Inibidores da Colinesterase/farmacologia , Crinum , Alcaloides de Amaryllidaceae/isolamento & purificação , Alcaloides de Amaryllidaceae/farmacologia , Butirilcolinesterase , Inibidores da Colinesterase/isolamento & purificação , Crinum/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais
14.
Nat Prod Res ; 35(5): 807-814, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30990078

RESUMO

Acetylcholinesterase (AChE) inhibitors remain the class of drugs used for the treatment of Alzheimer disease (AD). For the aim of discovering new sources of potent AChE inhibitors, a combined AChE-inhibitory activity together with alkaloid profiles by GC-MS, combined with multivariate statistical analysis for biomarkers determination and in silico studies were attempted. Strategy was applied on leaves, roots and bulbs of six aquatic and terrestrial Amaryllidaceae species. Thirty alkaloids were identified and the AChE inhibitory activities of the extracts were tested by in-vitro Ellman method. Principal bioactive markers were discovered by correlating AChE inhibitory activity with chemical fingerprints via PLS and OPLS modeling which revealed that galanthamine, lycoramine, caranine, tazettine and N-demethylgalanthamine were the most bio-significant markers. Furthermore, the molecular docking was performed to illustrate binding orientations of the top scoring alkaloids in the active site of human acetylcholinesterase. Suggested strategy revealed that, beside galanthamine, caranine, N-demethylgalanthamine, and lycoramine are promising AChE inhibitors.


Assuntos
Alcaloides/farmacologia , Amaryllidaceae/química , Inibidores da Colinesterase/farmacologia , Simulação por Computador , Crinum/química , Cromatografia Gasosa-Espectrometria de Massas , Acetilcolinesterase/metabolismo , Alcaloides/química , Doença de Alzheimer , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacologia , Domínio Catalítico , Inibidores da Colinesterase/química , Galantamina/química , Galantamina/farmacologia , Humanos , Simulação de Acoplamento Molecular , Análise Multivariada , Extratos Vegetais/química , Folhas de Planta/química , Raízes de Plantas/química
15.
J Asian Nat Prod Res ; 23(11): 1023-1029, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33118374

RESUMO

A phytochemical investigation on the 90% ethanol aqueous extract of the bulbs of Crinum latifolium led to the isolation of three new crinane-type alkaloids, designated as crinumlatines A-C (1-3). The structures of the new compounds were elucidated by spectroscopic analysis (NMR, IR, UV, and MS). The isolated alkaloids were tested in vitro for antimicrobial potentials against 5 pathogenic microorganisms. As a result, compounds 1-3 exhibited some antimicrobial activity against the tested Gram negative bacteria with minimum inhibitory concentration values less than 50 µg/ml.


Assuntos
Alcaloides , Alcaloides de Amaryllidaceae , Anti-Infecciosos , Crinum , Alcaloides/farmacologia , Estrutura Molecular , Extratos Vegetais
16.
Phytochemistry ; 179: 112485, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32861139

RESUMO

Four undescribed alkaloids have been isolated from the bulbs of the previously unstudied Crinum scillifolium. These compounds were targeted following a state-of-the-art molecular networking strategy comprising a dereplication against in silico databases and re-ranking of the candidate structures based on taxonomically informed scoring. The unreported structures span across a variety of Amaryllidaceae alkaloids appendages. Their structures were unambiguously elucidated by thorough interpretation of their HRESIMS and 1D and 2D NMR data, and comparison to literature data. DFT-NMR calculations were performed to support the determined relative configurations of scillitazettine and scilli-N-desmethylpretazettine and their absolute configurations were mitigated by comparison between experimental and theoretically calculated ECD spectra. The lack of a methyl group on the nitrogen atom in the structure of scilli-N-desmethylpretazettine series is highly unusual in the pretazettine/tazettine series but the most original structural feature in it lies in its 11α disposed hydrogen, which is new to pretazettines. The antiplasmodial as well as the cytotoxic activities against the human colon cancer cell line HCT116 were evaluated, revealing mild to null activities.


Assuntos
Alcaloides , Alcaloides de Amaryllidaceae , Crinum , Alcaloides/farmacologia , Alcaloides de Amaryllidaceae/farmacologia , Humanos , Estrutura Molecular , Extratos Vegetais , Raízes de Plantas
17.
Phytochemistry ; 175: 112390, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32335411

RESUMO

Three undescribed Amarylidaceae alkaloids, named gigantelline, gigantellinine and gigancrinine, were isolated from Crinum jagus (syn. = Crinum giganteum) collected in Senegal, together with the already known sanguinine, cherylline, lycorine, crinine, flexinine and the isoquinolinone derivative hippadine. Gigantelline, gigantellinine and gigancrinine were characterized as 4-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol, its 7-O-demethyl-5ꞌ-hydroxy-4ꞌ-methoxy derivative and 5,6a,7,7a,8a,9-hexahydro-6,9a-ethano[1,3]dioxolo[4,5-j]oxireno[2,3-b]phenanthridin-9-ol, respectively, by using spectroscopic (1D and 2D 1H and 13C NMR and HRESIMS) and chemical methods. Their relative configuration was assigned by NOESY NMR spectra and NMR calculations, while the absolute configuration was assigned using electronic circular dichroism (ECD) experiments and calculations. Sanguinine, cherylline, crinine, flexinine, and the isoquinolinone hippadine, were isolated for the first time from C. jagus. Cherylline, gigantellinine, crinine, flexinine and sanguinine inhibited the activity of AChE in a dose-dependent manner, and inhibition by sanguinine was remarkably effective (IC50 = 1.83 ±â€¯0.01 µM). Cherylline and hippadine showed weak cytotoxicity at 100 µM.


Assuntos
Alcaloides , Alcaloides de Amaryllidaceae , Crinum , Isoquinolinas , Estrutura Molecular
18.
Luminescence ; 35(2): 187-195, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31766074

RESUMO

We here in report the synthesis of gold nanoparticles (AuNPs) using a Crinum macowanii bulb water extract. The as-synthesized AuNPs were characterized using ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and a zeta potential-sizer. The results showed that the as-synthesized AuNPs were crystalline and mostly spherical in shape with a small mixture of triangular, tetrahedral, hexagonal, octagonal, and diamond shapes. The as-synthesized AuNPs together with those synthesized by conventional methods were subsequently used as enhancers for the luminol signal in blood detection. It was noted that the AuNPs synthesized from the Crinum macowanii bulb water extract could enhance the chemiluminescence signal for blood detection by luminol to the same extent as AuNPs prepared by conventional methods. Furthermore, both types of AuNPs served as fluorescence enhancers for blood detection when luminol was replaced with the bulb water extract.


Assuntos
Crime , Crinum/química , Ouro/química , Luminol/análise , Nanopartículas Metálicas/química , Extratos Vegetais/química , Humanos , Luminescência
19.
Biomolecules ; 9(9)2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527550

RESUMO

Crinumasiaticum is a perennial herb widely distributed in many warmer regions, including Thailand, and is well-known for its medicinal and ornamental values. Crinum alkaloids contain numerous compounds, such as crinamine. Even though its mechanism of action is still unknown, crinamine was previously shown to possess anticancer activity. In this study, we demonstrate that crinamine was more cytotoxic to cervical cancer cells than normal cells. It also inhibited anchorage-independent tumor spheroid growth more effectively than existing chemotherapeutic drugs carboplatin and 5-fluorouracil or the CDK9 inhibitor FIT-039. Additionally, unlike cisplatin, crinamine induced apoptosis without promoting DNA double-strand breaks. It suppressed cervical cancer cell migration by inhibiting the expression of positive regulators of epithelial-mesenchymal transition SNAI1 and VIM. Importantly, crinamine also exerted anti-angiogenic activities by inhibiting secretion of VEGF-A protein in cervical cancer cells and blood vessel development in zebrafish embryos. Gene expression analysis revealed that its mechanism of action might be attributed, in part, to downregulation of cancer-related genes, such as AKT1, BCL2L1, CCND1, CDK4, PLK1, and RHOA. Our findings provide a first insight into crinamine's anticancer activity, highlighting its potential use as an alternative bioactive compound for cervical cancer chemoprevention and therapy.


Assuntos
Alcaloides de Amaryllidaceae/administração & dosagem , Inibidores da Angiogênese/administração & dosagem , Crinum/química , Fatores de Transcrição da Família Snail/metabolismo , Neoplasias do Colo do Útero/metabolismo , Vimentina/metabolismo , Alcaloides de Amaryllidaceae/farmacologia , Inibidores da Angiogênese/farmacologia , Animais , Carboplatina/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Embrião não Mamífero/irrigação sanguínea , Embrião não Mamífero/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Extratos Vegetais/química , Piridinas/farmacologia , Neoplasias do Colo do Útero/irrigação sanguínea , Neoplasias do Colo do Útero/tratamento farmacológico , Peixe-Zebra/embriologia
20.
Microbiologyopen ; 8(12): e914, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31420951

RESUMO

The results from this study revealed that crude extracts isolated from bacterial endophytes obtained from Crinum macowanii bulbs showed activity against both Gram-positive and Gram-negative pathogenic bacteria, while Acinetobacter guillouiae crude extracts displayed anticancer activity. This study aimed to isolate and characterize bacterial endophytes and their crude extracts from C. macowanii bulbs. Endophytes were isolated using validated surface sterilization techniques, followed by phenotypic and genotypic profiles of the isolates. Crude extracts were extracted from the endophytes using ethyl acetate, while methanol:dichloromethane (1:1) was used to obtain crude extracts from the bulbs. Antibacterial activity of crude extract from each endophyte was investigated against selected pathogenic strains using the broth microdilution method, and anticancer activity against U87MG glioblastoma and A549 lung carcinoma cells was determined by the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Acinetobacter guillouiae, Pseudomonas moraviensis, Pseudomonas sp., Rahnella aquatilis, Bacillus cereus, Novosphingobium sp., Raoultella ornithinolytica, and Burkholderia tropica were successfully isolated. The crude extracts from the majority of endophytes showed antibacterial activity, ranging from 0.125 to >16.00 mg/ml against Gram-negative and Gram-positive pathogenic bacteria. Acinetobacter guillouiae extracts showed a high bioactive potential against U87MG glioblastoma cell lines by reducing their growth by 50% at concentrations of 12.5, 6.25, and 3.13 µg/ml. Crude extracts isolated from C. macowanii bulbs showed potential for possible drug lead against common pathogenic bacteria.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bactérias/química , Misturas Complexas/farmacologia , Crinum/microbiologia , Endófitos/química , Antibacterianos/química , Antineoplásicos/química , Bactérias/classificação , Bactérias/citologia , Bactérias/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Misturas Complexas/química , Endófitos/citologia , Humanos , Filogenia
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