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1.
Food Res Int ; 164: 112434, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36738001

RESUMO

Ferula assa-foetida is an important species of the genus Ferula, best known for its oleo-gum resin, mainly used as a flavoring agent. Ferula jaeschkeana is another Himalayan medicinal plant of this genus, known for its contraceptive effect but not used in food applications. This study aimed to do a detailed phytochemical analysis of F. assa-foetida growing under controlled conditions in India using GC-MS/headspace and UHPLC-PDA-QTOF-IMS. Further, a comparative analysis of F. assa-foetida was performed with F. jaeschkeana (collected from its natural habitat) and commercial samples of F. assa-foetida oleo-gum resin (collected from the local market). UHPLC-QTOF-IMS profiling of F. assa-foetida led to the identification of foetisulfide C, assafoetidnol A, gumosin, flabellilobin (A/B), and foetisulfide A. In total, 141 metabolites were identified, including vitamins, nucleosides, sulfur compounds, flavonoids, sugars derivatives, and others, using METLIN database. Serine, arginine, asparagine, isoleucine, and phenylalanine were major amino acids quantified among the samples for the nutritional aspect. Characteristic sulfurous compounds (n-propyl-sec-butyl disulfide, trans-propenyl-sec-butyl disulfide, cis-propenyl-sec-butyl disulfide, and bis[1-(methylthio)propyl] disulfide) were identified in all samples except F. jaeschkeana. PCA and cluster analysis showed a significant difference in the volatile constituents of rhizomes of both species. Metabolomics studies also revealed the association of sesquiterpenoid and triterpenoid biosynthesis, phenylpropanoid, flavon, and flavanol biosynthesis. The current study demonstrates, "why only F. assa-foetida is used in culinary applications instead of F. jaeschkeana"?


Assuntos
Ferula , Ferula/química , Cromatografia Gasosa-Espectrometria de Massas , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos , Compostos de Enxofre , Resinas Vegetais/química , Dissulfetos
2.
Indian J Pathol Microbiol ; 66(1): 191-195, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36656240

RESUMO

"Lineage switch" is term described when leukemic cells on relapse exhibit a new phenotype, where losses of one lineage defining markers with simultaneous gain of another lineage defining markers occur. Relapse of acute leukemia is although a very common event, lineage switch occurs and reported very rarely in such cases. The pathogenesis involved in this phenomenon remains unclear; however plasticity of hematopoietic progenitor affected by intrinsic and extrinsic environmental cues can be a possible explanation. In most of the cases at the time of relapse conversion of B-acute lymphoblastic leukemia (ALL) to acute myeloid leukemia (AML) occurs. Here, we presented an unusual case of 10 year old boy with AML switched to T-ALL upon relapse, which is very rare and not well documented till date in literature. The diagnosis was further supported by morphologic, cytochemistry and flowcytometric immunophenotyping (FCM-IPT). Prognosis and survival of such cases remains poor even by the use of standard chemotherapy.


Assuntos
Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Doença Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Recidiva , Linfócitos T/patologia , Imunofenotipagem
3.
J Biomol Struct Dyn ; 41(1): 55-66, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-34825633

RESUMO

Steroidal sapogenins (SS) are structural analogues of steroidal drugs, which are frequently used for the treatment of several diseases including reproductive, malignancies, neurological, and inflammation-related diseases. The glucocorticoid receptor (GR) is a nuclear receptor that regulates development, metabolism, and inflammation, in response to steroidal ligands. Therefore, GR is considered as a potential therapeutic target for steroidal agents to the treatment of inflammation-related diseases. We hypothesized that SS may act as an agonist for GR due to structural similarity with corticosteroids. In this study, we carried out in silico screening of various SS from the genus Trillium to check their potential as an agonist for GR. Our data suggest that out of 42 SS, only 7 molecules have interacted with GR. However, molecular mechanics with generalized Born and surface area (MM-GBSA) analysis revealed that only two SS (SS 38 and SS 39) molecules bind favorably to GR. Among these, SS 38 (docking score: -9.722 Kcal/mol and MM-GBSA ΔGbind: -50.192 Kcal/mol) and SS 39 (docking score: -11.20 Kcal/mol and MM-GBSA ΔGbind: -58.937 Kcal/mol) have best docking and MM-GBSA scores. Molecular dynamics (MD) simulation studies of SS 38, SS 39, and dexamethasone-GR complex revealed that both SS shows hydrogen bonding and hydrophobic interaction with GR over the 120 ns simulation with mild fluctuations. The current study suggests that SS 38 and SS 39 may be further explored as a potential agonist to treat several disease conditions mediated by GR.


Assuntos
Sapogeninas , Trillium , Humanos , Receptores de Glucocorticoides/química , Sapogeninas/farmacologia , Sapogeninas/metabolismo , Simulação de Acoplamento Molecular , Trillium/metabolismo , Simulação de Dinâmica Molecular , Inflamação , Ligantes
4.
Indian J Plast Surg ; 55(3): 282-286, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36325084

RESUMO

Background Abnormalities of fingernail growth and appearance are among the most common deformities encountered after burn injury to the hand. Various techniques used for resurfacing defects include incision of the scarred eponychium and advancement of the distal segment, flap reconstruction-distally, and proximally based transposition/advancement flaps, composite graft techniques, microvascular transfer. In the present study, we used an onion flap to release scarred eponychium and nail fold reconstruction in a single stage without using soft tissue from another area. Materials and methods Forty-four burnt fingers were operated using Yang's onion flap technique. Patients were assessed for flap necrosis, hematoma and infection in the early postoperative period and for donor site scar, nail appearance, and symptomatic relief in a follow-up for at least 4 months. Results The flap was successfully performed on all fingers. Only two fingers had flap necrosis. There was no incidence of hematoma or infection. The donor site scar and nail plate appearance improved and was acceptable to most patients after surgery. There was also significant relief in daily activities in 19 out of 28 symptomatic patients. Conclusion Yang's flap to correct nail deformities in burn patients is feasible in Indian scenario. It is associated with a low complication rate and improved nail appearance. There is also significant symptomatic relief in performing daily activities after surgery.

5.
Molecules ; 27(11)2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35684419

RESUMO

Onosma bracteata Wall. is an important medicinal and immunity-enhancing herbs. This plant is commonly used in the preparation of traditional Ayurvedic drugs to treat numerous diseases. Inspired by the medicinal properties of this plant, the present study aimed to investigate the antiproliferative potential and the primary molecular mechanisms of the apoptotic induction against human osteosarcoma (MG-63) cells. Among all the fractions isolated from O. bracteata, ethyl acetate fraction (Obea) showed good antioxidant activity in superoxide radical scavenging assay and lipid peroxidation assay with an EC50 value of 95.12 and 80.67 µg/mL, respectively. Silica gel column chromatography of ethyl acetate (Obea) fraction of O. bracteata yielded a pure compound, which was characterized by NMR, FTIR, and HR-MS analysis and was identified as 1,2-benzene dicarboxylic acid, bis (2-methyl propyl) ester (BDCe fraction). BDCe fraction was evaluated for the antiproliferative potential against human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung carcinoma A549 cell lines by MTT assay and exhibited GI50 values of 37.53 µM, 56.05 µM, and 47.12 µM, respectively. In MG-63 cells, the BDCe fraction increased the level of ROS and simultaneously decreased the mitochondria membrane potential (MMP) potential by arresting cells at the G0/G1 phase, suggesting the initiation of apoptosis. Western blotting analysis revealed the upregulation of p53, caspase3, and caspase9 while the expressions of p-NF-κB, p-Akt and Bcl-xl were decreased. RT-qPCR studies also showed upregulation in the expression of p53 and caspase3 and downregulation in the expression of CDK2, Bcl-2 and Cyclin E genes. Molecular docking analysis displayed the interaction between BDCe fraction with p53 (-151.13 kcal/mol) and CDK1 (-133.96 kcal/mol). The results of the present work suggest that the BDCe fraction has chemopreventive properties against osteosarcoma (MG-63) cells through the induction of cell cycle arrest and apoptosis via Akt/NF-κB/p53 pathways. This study contributes to the understanding of the utilization of BDCe fraction in osteosarcoma treatment.


Assuntos
Neoplasias Ósseas , Boraginaceae , Osteossarcoma , Apoptose , Boraginaceae/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Ésteres , Humanos , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Osteossarcoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Supressora de Tumor p53/metabolismo
6.
Molecules ; 27(3)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35163898

RESUMO

Aphis craccivora Koch is a polyphagous and major pest of leguminous crops causing significant damage by reducing the yield. Repeated application of synthetic insecticides for the control of aphids has led to development of resistance. Therefore, the present study aimed to screen the insecticidal activity of root/stem extracts/fractions, and pure molecules from Cissampelos pareira Linnaeus against A. craccivora for identification of lead(s). Among root extract/fractions, the n-hexane fraction was found most effective (LC50 = 1828.19 mg/L) against A. craccivora, followed by parent extract (LC50 = 2211.54 mg/L). Among stem extract/fractions, the n-hexane fraction (LC50 = 1246.92 mg/L) was more effective than the water and n-butanol fractions. Based on GC and GC-MS analysis, among different compounds identified in the n-hexane fraction of root and stem, ethyl palmitate (known to possess insecticidal activity) was present in the highest concentration (24.94 to 52.95%) in both the fractions. Among pure molecules, pareirarineformate was found most effective (LC50 = 1491.93 mg/L) against A. craccivora, followed by cissamine (LC50 = 1556.31 mg/L). Parent extract and fractions of C. pareira possess promising activity against aphid. Further, field bio-efficacy studies are necessary to validate the current findings for the development of botanical formulation.


Assuntos
Afídeos , Cissampelos , Inseticidas , Animais , Inseticidas/farmacologia , Extratos Vegetais/farmacologia
7.
Indian J Cancer ; 59(1): 110-114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35017367

RESUMO

Non-immunoglobulin intracytoplasmic inclusions in plasma cells of multiple myeloma are very rare presentation. These are morphologically similar to Auer rods but chemically different from them. We studied two cases of multiple myeloma in a 60-year-old woman and 45-year-old man. In both cases, plasma cells of bone marrow aspirate revealed multiple Auer rod-like inclusions (ARLI). Sudan black B (SBB) and myeloperoxidase (MPO) cytochemistry were negative. Serum protein electrophoresis in both of them showed M spike, one with raised IgA-kappa levels, while the other with raised IgG-kappa levels. Very few case reports have been published in the literature and its prognostic implications are still unknown. Due to its rarity, it is important to distinguish such cases from acute myeloid leukemia and its exact incidence with its therapeutic and prognostic implications.


Assuntos
Mieloma Múltiplo , Feminino , Humanos , Corpos de Inclusão , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Plasmócitos , Prognóstico
8.
Sci Rep ; 11(1): 20095, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635729

RESUMO

Bioactive fractions obtained from medicinal plants which have been used for the treatment of multiple diseases could exert their effects by targeting common pathways. Prior knowledge of their usage could allow us to identify novel molecular links. In this study, we explored the molecular basis of action of one such herbal formulation Cissampelos pareira L. (Cipa), used for the treatment of female hormone disorders and fever. Transcriptomic studies on MCF7 cell lines treated with Cipa extract carried out using Affymetrix arrays revealed a downregulation of signatures of estrogen response potentially modulated through estrogen receptor α (ERα). Molecular docking analysis identified 38 Cipa constituents that potentially bind (ΔG < - 7.5) with ERα at the same site as estrogen. The expression signatures in the connectivity map ( https://clue.io/; ) revealed high positive scores with translation inhibitors such as emetine (score: 99.61) and knockdown signatures of genes linked to the antiviral response such as ribosomal protein RPL7 (score: 99.92), which is a reported ERα coactivator. Further, gene knockdown experiments revealed that Cipa exhibits antiviral activity in dengue infected MCF7 cells potentially modulated through estrogen receptor 1. This approach reveals a novel pathway involving the ESR1-RPL7 axis which could be a potential target in dengue viral infection.


Assuntos
Antivirais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Cissampelos/química , Dengue/tratamento farmacológico , Receptor alfa de Estrogênio/metabolismo , Extratos Vegetais/farmacologia , Transcriptoma/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/virologia , Dengue/metabolismo , Dengue/patologia , Dengue/virologia , Vírus da Dengue , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Células MCF-7
9.
J Mol Graph Model ; 106: 107916, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33892297

RESUMO

The life challenging COVID-19 disease caused by the SARS-CoV-2 virus has greatly impacted smooth survival worldwide since its discovery in December 2019. Currently, it is one of the major threats to humanity. Moreover, any specific drug or vaccine unavailability against COVID-19 forces to discover a new drug on an urgent basis. Viral cycle inhibition could be one possible way to prevent the further genesis of this viral disease, which can be contributed by drug repurposing techniques or screening of small bioactive natural molecules against already validated targets of COVID-19. The main protease (Mpro) responsible for producing functional proteins from polyprotein is an important key step for SARS-CoV-2 virion replication. Natural product or herbal based formulations are an important platform for potential therapeutics and lead compounds in the drug discovery process. Therefore, here we have screened >53,500 bioactive natural molecules from six different natural product databases against Mpro (PDB ID: 6LU7) of COVID-19 through computational study. Further, the top three molecules were subjected to pharmacokinetics evaluation, which is an important factor that reduces the drug failure rate. Moreover, the top three screened molecules (C00014803, C00006660, ANLT0001) were further validated by a molecular dynamics study under a condition similar to the physiological one. Relative binding energy analysis of three lead molecules indicated that C00014803 possess highest binding affinity among all three hits. These extensive studies can be a significant foundation for developing a therapeutic agent against COVID-19 through vet lab studies.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Simulação de Acoplamento Molecular , Inibidores de Proteases , Proteínas não Estruturais Virais
10.
J Pharm Pharmacol ; 73(4): 487-495, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33793831

RESUMO

OBJECTIVE: To provide the scientific basis for the utility of rhizome of Trillium govanianum as nutraceutical supplements in managing physiological glycemic levels. METHODS: The in vitro enzyme inhibitory activity of the extract, fractions, and the isolated steroidal saponins from the rhizome part of T. govanianum was carried out against α-amylase, α-glucosidase, and dipeptidyl peptidase IV. The molecular interactions, binding score, and pharmacokinetic parameters (absorption, distribution metabolism, and excretion) of steroidal saponins were analyzed by the Schrodinger molecular docking software. KEY FINDINGS: Current study explained that the extract, fractions, and isolated steroidal saponins from T. govanianum possess good α-amylase and α-glucosidase inhibitory activity while moderate dipeptidyl peptidase IV inhibitory activity. Moreover, in vitro results revealed that borassoside E (IC50 7.15 ± 1.78 µM), protodioscin (IC50 6.72 ± 0.04 µM), and diosgenin (IC50 12.75 ± 2.70 µM) are most effective in inhibiting the activity of α-amylase, α-glucosidase, and dipeptidyl peptidase IV, respectively. Current in silico and in vitro studies established an association between the steroidal saponins from T. govanianum and their molecular interactions with α-amylase, α-glucosidase, and dipeptidyl peptidase IV. CONCLUSION: The results of this investigation suggest that fractions and steroidal saponins from T. govanianum exhibit good antidiabetic activity which could be used as nutraceutical supplements for the management of systemic glucose level.


Assuntos
Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes , Saponinas/farmacologia , Trillium/química , alfa-Amilases/antagonistas & inibidores , Dipeptidil Peptidase 4/análise , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Técnicas In Vitro , Simulação de Acoplamento Molecular/métodos , Extratos Vegetais/farmacologia , Rizoma/química , alfa-Amilases/análise , alfa-Glucosidases/análise
12.
J Ethnopharmacol ; 274: 113850, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-33485976

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cissampelos pareira, a well-known medicinal climber-plant of the Menispermaceae family, has been extensively used in the traditional medicinal system since the ancient time for the treatment of numerous diseases such as ulcer, wound, rheumatism, fever, asthma, cholera, diarrhoea, inflammation, snakebite, malaria, rabies, and also recommended for blood purification. AIM OF THE REVIEW: The main purpose of this review is to provide updated information on ethnopharmacology, phytochemistry, chromatographic and spectroscopic analysis, pharmacology, and toxicology of C. pareira along with the possible future research. This information will help to provide a foundation for plant-based drug discovery in the near future. MATERIAL AND METHODS: The online databases such as Scifinder, Web of Science, PubMed, and Google Scholar were used to collect electronically available literature data on C. pareira. Ayurveda text is searched for the traditional uses of this plant in India. The published books are also searched for the information on this plant. Our search was based on traditional uses, botany, phytochemistry, and pharmacological potential by using "Cissampelos pareira" as the keyword. RESULTS: To date, approximately 54 phytomolecules have been isolated and characterized from C. pareira including mainly isoquinoline alkaloids along with few flavonoids, flavonoid glycosides, and fatty acids. The crude extracts of C. pareira have shown various pharmacological activities such as antipyretic, anti-inflammatory, antiarthritic, antiulcer, antidiabetic, anticancer, antifertility, antimicrobial, antioxidant, antivenom, antimalarial, and immunomodulatory, etc. The chemical fingerprinting of C. pareira carried out using HPTLC, HPLC, UPLC, LC-MS, and GC-MS, revealed the presence of alkaloids (isoquinoline alkaloids), fatty acids, and flavonoid glycosides. Moreover, the toxicological assessment of C. pareira has been moderately investigated, which requires further comprehensive studies. CONCLUSION: Comprehensive literature survey reveals that till date, remarkable growth has been made on phytochemistry and pharmacology of C. pareira reflecting the great medicinal potential of this plant. Although some of the traditional uses have been well clarified and documented by modern pharmacological analysis, the correlation between its pharmacological activities and particular phytoconstituents still needs to be validated. Furthermore, there is partial data available on most of the pharmacological studies, along with incomplete toxicological screening. Future research needs to pay more attention to pharmacological studies of C. pareira via pre-clinical and clinical trials. Additionally, scientific validation of traditional knowledge of C. pareira is vital for ensuring safety, efficacy, and mechanism of action before clinical uses.


Assuntos
Cissampelos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Animais , Bases de Dados Factuais , Humanos , Ayurveda , Compostos Fitoquímicos/química , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Plantas Medicinais/química , Plantas Medicinais/toxicidade
13.
Antioxidants (Basel) ; 9(2)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093300

RESUMO

: Cassia fistula L. is a highly admirable traditional medicinal plant used for the treatment of various diseases and disorders. The present study was performed to divulge the antioxidant, antiproliferative, and apoptosis-inducing efficacy of fractions from C. fistula leaves. The hexane (CaLH fraction), chloroform (CaLC fraction), ethyl acetate (CaLE fraction), n-butanol (CaLB fraction), and aqueous (CaLA fraction) were sequentially fractionated from 80% methanolic (CaLM extract) of C. fistula leaves. The CaLE fraction was fractionated using column chromatography to yield a pure compound, which was characterized as Epiafzelechin (CFL1) based on 1H, 13C, and DEPT135 NMR. Among these fractions, CaLE and isolated CFL1 fractions exhibited an effective antioxidant potential in Ferric ion reducing power, (2,2'-azino-bis (3-ethylbenzothiazoline -6-sulfonic acid)) cation radical scavenging, and nitric oxide radical scavenging assays. Epiafzelechin was investigated for its antiproliferative effects against MG-63 (osteosarcoma), IMR-32 (neuroblastoma), and PC-3 (prostate adenocarcinoma), and was found to inhibit cell proliferation with a GI50 value of 8.73, 9.15, and 11.8 µM respectively. MG-63 cells underwent apoptotic cell death on treatment with Epiafzelechin as the cells showed the formation of apoptotic bodies, enhanced reactive oxygen species (ROS) generation, mitochondrial membrane depolarization along with an increase in early apoptotic cell population analyzed using Annexin V-FITC/PI double staining assay. Cells showed cell cycle arrest at the G0/G1 phase accompanied by a downregulation in the expression levels of p-Akt (Protein kinase B), p-GSK-3ß (Glycogen synthase kinase-3 beta), and Bcl-xl (B-cell lymphoma-extra large) proteins. RT-PCR (Real time-polymerase chain reaction) analysis revealed downregulation in the gene expression level of ß-catenin and CDK2 (cyclin-dependent kinases-2) while it upregulated the expression level of caspase-8 and p53 genes in MG-63 cells.

14.
Nat Prod Res ; 34(2): 233-240, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30636443

RESUMO

A new narciclasine glycoside, narciclasine-4-O-ß-D-xylopyranoside (1) was characterised along with four known alkaloids pancratistatin (2), 1-O-(3-hydroxybutyryl) pancratistatin (3), vittatine (4), 9-O-demethylgalanthine (5) from Zephyranthes minuta. Their structures were established on the basis of spectroscopic data analysis. The in vitro cytotoxic study of extract, fractions and isolated compounds against two human cancer cell lines (KB and SiHa) indicated the potential activity of extract and n-butanol fraction due to presence of active alkaloids pancratistatin, 1-O-(3-hydroxybutyryl) pancratistatin, lycorine and haemanthamine.


Assuntos
Alcaloides de Amaryllidaceae/isolamento & purificação , Amaryllidaceae/química , Glicosídeos/isolamento & purificação , Fenantridinas/isolamento & purificação , Alcaloides/química , Alcaloides/farmacologia , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacologia , Glicosídeos Cardíacos , Linhagem Celular Tumoral , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Glicosídeos/química , Humanos , Isoquinolinas/farmacologia , Fenantridinas/química , Fenantridinas/farmacologia , Extratos Vegetais/química
15.
Nat Prod Res ; 34(14): 2051-2058, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30784301

RESUMO

A new N-oxide, Pseudolycorine N-oxide (1) was characterised along with eleven known alkaloids homolycorine (2), O-methylmaritidine (3), 8-O-demethylhomolycorine (4), homolycorine N-oxide (5), lycorine (6), narciclasine (7), pseudolycorine (8), ungeremine (9), 8-O-demethylmaritidine (10), zefbetaine (11) and lycorine N-oxide (12), from Narcissus tazetta. Their structures were established on the basis of spectroscopic data analysis. The extract, fractions and isolated compounds were screened for in vitro cytotoxicity against two human cancer cell lines, human cervical cancer (SiHa) and human epidermoid carcinoma (KB) cells. The study demonstrated the cytotoxic potential of extract and its chloroform and n-butanol fractions. Further, the results revealed the bioactive potential of narciclasine, pseudolycorine and homolycorine alkaloids. However, new N-oxide (1) was not active against these cell lines.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides de Amaryllidaceae/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Narcissus/química , Óxidos/isolamento & purificação , Fenantridinas/isolamento & purificação , Extratos Vegetais/química , Alcaloides/química , Alcaloides de Amaryllidaceae/análise , Alcaloides de Amaryllidaceae/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Indolizinas/análise , Óxidos/química , Fenantridinas/análise , Fenantridinas/química
16.
J Pharm Biomed Anal ; 175: 112750, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31330284

RESUMO

Narcissus tazetta is used traditionally for treatment of sores, wounds, skin diseases, cancer in different parts of world. Present study focus on the analysis of amaryllidaceae alkaloids in this plant using an ultra-performance liquid chromatography-diode array detection method. The method was developed for simultaneous quantification of eight Amaryllidaceae alkaloids i.e. pseudolycorine (1), lycorine (2), galanthamine (3), 8-O-demethylhomolycorine (4), N-methylhaemanthidine chloride (5), homolycorine (6), narciclasine (7) and zefbetaine (8) in Narcissus tazetta. The method was validated using a BEH C18 column with linear gradient. Standard calibration curve for the analytes showed good linearity ( r2≥0.999). The method was validated for intra-day (RSDs<0.91%) and inter-day (RSDs<0.65%) precisions and accuracy (recovery 92.2-112.5%). The developed method was successively applied for studying the variation of alkaloids in different parts of Narcissus tazetta, i.e. bulbs, roots, flowers, flower stalks and leaves. The study showed a significant variation of these alkaloids in different parts of the plant. Among the alkaloids under investigation, pseudolycorine had highest content in all the parts. Furthermore, application of the developed method to the identification of phytocomponents allowed the identification of sixteen alkaloids.


Assuntos
Alcaloides de Amaryllidaceae/química , Narcissus/química , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão/métodos , Flores/química , Galantamina/química , Fenantridinas/química , Folhas de Planta/química , Raízes de Plantas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
17.
J Org Chem ; 83(20): 12702-12710, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30211555

RESUMO

Here, a facile and efficient protocol for the synthesis of 3-hydroxyquinolin-8-yl propanoates via Rh(III)-catalyzed C(8)-H activation of 2-substituted quinolines has been developed. The reaction proceeds via C(8)-H activation, functionalization with acrylates, followed by intramolecular migration of the oxygen atom from quinoline N-oxides to the acrylate moiety. In this approach, N-oxide plays a dual role of a traceless directing group as well as a source of an oxygen atom for hydroxylation. This catalytic method involves simultaneous formation of new C-C and C-O bonds and is applicable only for C2-substituted quinolines. A catalytically competent five-membered rhodacycle has been characterized, thus revealing a key intermediate in the catalytic cycle. In silico docking studies against Falcipan-2 have revealed that 3a, 3b, 3g, and 3m have better scores. In vitro evaluation of selected compounds against CQ-sensitive pf3D7 and CQ-resistant pfINDO strains provided evidence that 3d (IC50 13.3 µM) and 3g (IC50 9.5 µM) had good promise against Plasmodium falciparum in the in vitro culture. Compound 3g was found to be the most potent on the basis of both in vitro antiplasmodial activity [IC50 9.5 µM ( Pf3D7) and 11.9 µM ( PfINDO), resistance index 1.25] and in silico studies.


Assuntos
Antimaláricos/síntese química , Antimaláricos/farmacologia , Quinolinas/síntese química , Quinolinas/farmacologia , Ródio/química , Catálise , Óxidos N-Cíclicos/química , Cisteína Endopeptidases/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Simulação de Acoplamento Molecular , Estrutura Molecular , Plasmodium falciparum/efeitos dos fármacos , Ligação Proteica , Relação Estrutura-Atividade
18.
Eur J Med Chem ; 155: 623-638, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29929118

RESUMO

The inherent affinity of natural compounds for biological receptors has been comprehensively exploited with great success for the development of many drugs, including antimalarials. Here the natural flavoring compound vanillin has been used as an economical precursor for the synthesis of a series of novel bischalcones whose in vitro antiplasmodial activities have been evaluated against erythrocytic stages of Plasmodium falciparum. Bischalcones 9, 11 and 13 showed promising antiplasmodial activity {Chloroquine (CQ) sensitive Pf3D7 IC50 (µM): 2.0, 1.5 and 2.5 respectively}but only 13 displayed potent activities also against CQ resistant PfDd2 and PfIndo strains exhibiting resistance indices of 1.4 and 1.5 respectively. IC90 (8 µM) of 13 showed killing activity against ring, trophozoite and schizont stages. Further, 13 initiated the cascade of reactions that culminates in programmed cell death of parasites including translocation of phosphatidylserine from inner to outer membrane leaflet, loss of mitochondrial membrane potential, activation of caspase like enzyme, DNA fragmentation and chromatin condensation. The combinations of 13 + Artemisinin (ART) exhibited strong synergy (ΣFIC50:0.46 to 0.58) while 13 + CQ exhibited mild synergy (ΣFIC50: 0.7 to 0.98) to mild antagonism (ΣFIC50: 1.08 to 1.23) against PfIndo. In contrast, both combinations showed marked antagonism against Pf3D7(ΣFIC50: 1.33 to 3.34). These features of apoptosis and strong synergy with Artemisinin suggest that bischalcones possess promising antimalarial drug-like properties and may also act as a good partner drugs for artemisinin based combination therapies (ACTs) against Chloroquine resistant P. falciparum.


Assuntos
Antimaláricos/farmacologia , Apoptose/efeitos dos fármacos , Artemisininas/farmacologia , Benzaldeídos/farmacologia , Chalconas/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/síntese química , Antimaláricos/química , Artemisininas/química , Benzaldeídos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chalconas/síntese química , Chalconas/química , Cloroquina/química , Cloroquina/farmacologia , Relação Dose-Resposta a Droga , Resistência a Medicamentos/efeitos dos fármacos , Células HeLa , Humanos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade
19.
J Plast Reconstr Aesthet Surg ; 71(8): 1159-1163, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29724622

RESUMO

Scars have multiple cosmetic and functional sequelae, and revision surgeries are an attempt to ameliorate these effects. Reduction of spread of the revised scar is one of the main objectives of revision procedures. Provision of prolonged dermal support to wound can theoretically reduce spread of the scar. We carried out a randomized controlled trial and objectively evaluated the impact of two commonly used absorbable sutures, Polyglactin 910 and Polydioxanone, on scar spread and quality. Sixty patients with post-traumatic scars of 1 year in duration were enrolled in the study and randomly divided into two groups of 30 each. After recording the demographic data and baseline scar characteristics, revision of the scar was carried out by elliptical excision and primary suturing. In Group 1, Polyglactin 910 6-0 suture (Vicryl, Ethicon, Johnson and Johnson Ltd., India) was used for dermal suturing, whereas, in Group 2, Polydioxanone 6-0 suture (PDS II, Ethicon, Johnson and Johnson Ltd., India) was used. The scar spread in terms of scar width, and scar quality with Vancouver Scar Scale (VSS) was evaluated at 1, 3 and 4 months postoperatively. The two groups were well matched for demographics and baseline scar characteristics. On follow-up, the mean scar width in Group 1 was significantly more than that in Group 2. VSS score was significantly lower in Group 2 at the third and fourth month follow up, signifying better scar quality. Suture extrusion was noticed in 3 cases in Group 1. Compared to Polyglactin 910, Polydioxanone sutures, when used for intradermal suturing in revision of facial scars, result in a significantly decreased scar spread and better scar quality.


Assuntos
Cicatriz/cirurgia , Polidioxanona , Poliglactina 910 , Técnicas de Sutura/instrumentação , Suturas , Cicatrização , Adolescente , Adulto , Cicatriz/diagnóstico , Desenho de Equipamento , Face , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reoperação , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
J Food Sci Technol ; 55(5): 1806-1815, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29666533

RESUMO

Natural foods are used in many folks and household treatments and have immense potential to treat a serious complication and health benefits, in addition to the basic nutritional values. These food products improve health, delay the aging process, increase life expectancy, and possibly prevent chronic diseases. Purple head Brassica oleracea L. var. italica Plenck is one of such foods and in current studies was explored for chemical compounds at different development stages by gas chromatography-mass spectrometry. Antioxidant potential was explored employing different assays like molybdate ion reduction, DPPH, superoxide anion radical scavenging and plasmid nicking assay. Inspired by antioxidant activity results, we further explored these extracts for antiproliferative potential by morphological changes, cell cycle analysis, measurement of intracellular peroxides and mitochondrial membrane potential changes. Current study provides the scientific basis for the use of broccoli as easily affordable potent functional food.

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