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1.
Mol Pharm ; 21(5): 2577-2589, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38647021

RESUMO

This study aimed to repurpose the antifungal drug flucytosine (FCN) for anticancer activity together with cocrystals of nutraceutical coformers sinapic acid (SNP) and syringic acid (SYA). The cocrystal screening experiments with SNP resulted in three cocrystal hydrate forms in which two are polymorphs, namely, FCN-SNP F-I and FCN-SNP F-II, and the third one with different stoichiometry in the asymmetric unit (1:2:1 ratio of FCN:SNP:H2O, FCN-SNP F-III). Cocrystallization with SYA resulted in two hydrated cocrystal polymorphs, namely, FCN-SYA F-I and FCN-SYA F-II. All the cocrystal polymorphs were obtained concomitantly during the slow evaporation method, and one of the polymorphs of each system was produced in bulk by the slurry method. The interaction energy and lattice energies of all cocrystal polymorphs were established using solid-state DFT calculations, and the outcomes correlated with the experimental results. Further, the in vitro cytotoxic activity of the cocrystals was determined against DU145 prostate cancer and the results showed that the FCN-based cocrystals (FCN-SNP F-III and FCN-SYA F-I) have excellent growth inhibitory activity at lower concentrations compared with parent FCN molecules. The prepared cocrystals induce apoptosis by generating oxidative stress and causing nuclear damage in prostate cancer cells. The Western blot analysis also depicted that the cocrystals downregulate the inflammatory markers such as NLRP3 and caspase-1 and upregulate the intrinsic apoptosis signaling pathway marker proteins, such as Bax, p53, and caspase-3. These findings suggest that the antifungal drug FCN can be repurposed for anticancer activity.


Assuntos
Antifúngicos , Antineoplásicos , Apoptose , Reposicionamento de Medicamentos , Flucitosina , Neoplasias da Próstata , Transdução de Sinais , Apoptose/efeitos dos fármacos , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Antifúngicos/farmacologia , Antifúngicos/química , Masculino , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Reposicionamento de Medicamentos/métodos , Flucitosina/farmacologia , Flucitosina/química , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Ácido Gálico/química , Ácido Gálico/farmacologia , Ácido Gálico/análogos & derivados , Cristalização , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
2.
Bioorg Chem ; 105: 104459, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33217632

RESUMO

In the present study, the titanium decorated iron oxide (Ti@Fe2O3) nanocomposites are synthesized using the chemical method. The as-prepared nanocomposite was characterized for successful formulation and the elemental spectra showed the composition of Fe (44%), Ti (0.71%) and O (55%) is confirmed the homogenous distribution. Crystallographic spectra depict the strong peaks corresponding to the of TiO2 and Fe2O3 nanoparticles planes with minor shift variation due to the formulation of Ti on the surface of Fe2O3 nanoparticles and it is also confirmed with SAED analysis. The X-ray photoelectron spectroscopy (XPS) analysis of Ti@Fe2O3) nanocomposite confirms the existence of elements such as Fe, O and Ti. Further, the morphology of the composite showed the well-defined encapsulation and aggregation of TiO2 nanoparticles on the surface of Fe2O3 nanoparticles. Further, the TiO2 nanoparticles showed less cytotoxic activity against bovine satellite cells, as well the nanocomposite increased the growth of bovine satellite cells comparing with control cells. Further, the morphological analysis showed the significant changes in TiO2 nanoparticles treated cells and the nanocomposite induces the myotube formation due to the increased ROS level in bovine satellite cells. Moreover, the nanocomposite regulates the expression of genes IGF-1, TGF-ß, MSTN, CASP3, CASP2 and proteins such as CALP1, CALP2, MyoD, MyoG which are responsible for the growth, proliferation, and differentiation of satellite cells. Together, the prepared Ti@Fe2O3 nanocomposites afford additional support for the applications of nanomaterials in skeletal muscle repair and tissue regeneration engineering.


Assuntos
Compostos Férricos/química , Nanopartículas Metálicas/química , Nanocompostos/química , Estresse Oxidativo/efeitos dos fármacos , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Titânio/química , Animais , Bovinos , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Regeneração , Engenharia Tecidual , Alicerces Teciduais/química
3.
Microb Pathog ; 132: 343-354, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31100406

RESUMO

In the present study, an attempt has been made to explore the antibiofilm activity of bioactive compound 1-hydroxy-1-norresistomycin (HNM) derived from coral mucus associated actinomycete Streptomyces variabilis. Initially, different concentration of HNM inhibited the biofilm formation of human clinical pathogens Escherichia coli, Vibrio cholerae and Staphylococcus aureus was determined using crystal-violet staining assay. The light microscopic analysis showed that HNM reduced the biofilm formation and adherence of bacterial cells on the surface of coverslip. HNM also damages the 3D architecture with reduced thickness as well as cell aggregation of biofilm forming bacteria analysed by confocal laser scanning microscopy (CLSM). In addition, HNM also demonstrated the efficiency in inhibiting theoretical adhesion by altering the surface hydrophobicity that can potentially hamper cellular adhesion and prevent biofilm formation. Furthermore, the molecular docking showed the significant interaction between HNM and key biofilm forming proteins proved an excellent antibiofilm activity of HNM. Together, these results suggest that the HNM can serve as potential antibiofilm agent in controlling the infections of E. coli, V. cholerae and S. aureus.


Assuntos
Biofilmes/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Pirenos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Vibrio cholerae/efeitos dos fármacos , Actinobacteria/metabolismo , Animais , Antozoários/microbiologia , Fator de Transcrição AraC/efeitos dos fármacos , Aderência Bacteriana/efeitos dos fármacos , Proteínas de Bactérias/efeitos dos fármacos , Simulação por Computador , Cisteína Endopeptidases/efeitos dos fármacos , Proteínas de Escherichia coli/efeitos dos fármacos , Humanos , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Pirenos/química , Streptomyces/metabolismo , Transativadores/efeitos dos fármacos , Peixe-Zebra
4.
Bioorg Chem ; 83: 326-335, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30396117

RESUMO

Graphene oxide (GO) has been recently attracted considerable interest for its potential applications in physical, chemical and biological properties. In the present study, the GO nanosheets were prepared by a chemical exfoliation technique using a modified Hummers method. Initially, the prepared GO nanosheets were confirmed by UV-vis spectroscopy and further characterized by FE-SEM, Edax, HR-TEM and SAED that demonstrated the formation of GO nanosheets with few layers flat sheet structure with hexagonal lattice crystalline nature. The FTIR spectra revealed the presence of various oxygen containing functional groups has been produced from graphite plane by exfoliation technique. The prepared GO nanosheets showed excellent antibiotic resistant activity against planktonic bacteria and more effective to damage the established biofilms and inhibits the biofilm formation of human clinical pathogens like E. coli and P. aeruginosa. Further, the GO nanosheets were found to be non-toxic to normal mammalian cells and there are no apparent morphological changes were observed in control and treated cells. In conclusion, GO nanosheets were effectively preventing the formation of biofilms and kills the represent bacteria that suggested the GO nanosheets could be used for the prevention and treatment of biofilm-related infections.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Grafite/farmacologia , Nanoestruturas/química , Antibacterianos/síntese química , Antibacterianos/toxicidade , Escherichia coli/efeitos dos fármacos , Grafite/síntese química , Grafite/toxicidade , Nanoestruturas/toxicidade , Pseudomonas aeruginosa/efeitos dos fármacos
5.
Colloids Surf B Biointerfaces ; 234: 113763, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38262106

RESUMO

In the present study, the vanadium pentoxide (V2O5) nickel-doped vanadium pentoxide (Ni@V2O5) was prepared and determined for in vitro anticancer activity. The structural characterization of the prepared V2O5 and Ni@V2O5 was determined using diverse morphological and spectroscopic analyses. The DRS-UV analysis displayed the absorbance at 215 nm for V2O5 and 331 nm for Ni@V2O5 as the primary validation of the synthesis of V2O5 and Ni@V2O5. The EDS spectra exhibited the presence of 30% of O, 69% of V, and 1% of Ni and the EDS mapping showed the constant dispersion. The FE-SEM and FE-TEM analysis showed the V2O5 nanoparticles are rectangle-shaped and nanocomposites have excellent interfaces between nickel and V2O5. The X-ray photoelectron spectroscopy (XPS) investigation of Ni@V2O5 nanocomposite endorses the occurrence of elements V, O, and Ni. The in vitro MTT assay clearly showed that the V2O5 and Ni@V2O5 have significantly inhibited the proliferation of B16F10 skin cancer cells. In addition, the nanocomposite produces the endogenous reactive oxygen species in the mitochondria, causes the mitochondrial membrane and nuclear damage, and consequently induces apoptosis by caspase 9/3 enzymatic activity in skin cancer cells. Also, the western blot analysis showed that the nanocomposite suppresses the oncogenic marker proteins such as PI3K, Akt, and mTOR in the skin cancer cells. Together, the results showed that Ni@V2O5 can be used as an auspicious anticancer agent against skin cancer.


Assuntos
Nanocompostos , Neoplasias Cutâneas , Compostos de Vanádio , Humanos , Fosfatidilinositol 3-Quinases , Níquel/farmacologia , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Espectroscopia Fotoeletrônica , Apoptose , Neoplasias Cutâneas/tratamento farmacológico
6.
Biochem Pharmacol ; 218: 115915, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37949323

RESUMO

The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to the release of pro-inflammatory cytokines and is essential for innate defence against infection and danger signals. These secreted cytokines improve the inflammatory response caused by tissue damage and associated inflammation. Consequently, the development of NLRP3 inflammasome inhibitors are viable option for the treatment of diverse inflammatory disorders. The significant anti-inflammatory effects of the NLRP3 inhibitors have severe side effects. Hence, the application of NLRP3 inhibitors against inflammatory disease has not yet been understood and most of the developed inhibitors are unsuccessful in clinical trials. The processes behind the NLRP3 complex, priming, and activation are the main emphasis of this review, which also covers therapeutical inhibitors of the NLRP3 inflammasome and potential therapeutic strategies for directing the NLRP3 inflammasome towards clinical development.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamação/tratamento farmacológico , Citocinas
7.
Chem Biol Interact ; 369: 110282, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36427553

RESUMO

The present study aims to investigate the effect and the molecular mechanism of N-(2-hydroxyphenyl)-2-phenazinamine (NHP) isolated from Nocardiopsis exhalans against the proliferation of human lung cancer cells. The cytotoxic activity of NHP against A549 and H520 cells was determined using MTT assay. The cytotoxic activity of NHP against A549 and H520 lung cancer cells showed excellent activity at 75 µg/mL and damage the mitochondrial membrane and nucleus by generating oxidative stress. NHP causes nuclear condensation and induces apoptosis which was confirmed using AO/EB and PI/DAPI dual staining assay. Moreover, the NHP downregulates the oncogenic genes such as IL-8, TNFα, MMPs and BcL2 and also upregulates the expression of apoptosis marker genes such as Cyto C, p53, p21, caspase 9/3 in A549 and H520 human lung cancer cells. Considering the strong anticancer activity of NHP against lung cancer, NHP may be further evaluated as a potential anticancer drug for the treatment of lung cancer.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Apoptose , Antineoplásicos/uso terapêutico , Células A549 , Proliferação de Células
8.
Food Res Int ; 171: 112993, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37330843

RESUMO

The comprehensive metabolic profiling was performed in the leaf extracts of Mangifera indica and assessed for their significant therapeutic application in tissue engineering and regenerative medicine in both in vitro and in vivo studies. About 147 compounds were identified in the ethyl acetate and methanol extracts of M. indica using MS/MS fragmentation analysis and the selected compounds were quantified using LC-QqQ-MS analysis. The in vitro cytotoxic activity showed that the M. indica extracts enhance the proliferation of mouse myoblast cells in concentration-dependent manner. As well, the extracts of M. indica induce the myotube formation by generating oxidative stress in the C2C12 cells was confirmed. The western blot analysis clearly showed that the M. indica induce myogenic differentiation by upregulating the myogenic marker proteins such as PI3K, Akt, mTOR, MyoG, and MyoD. The in vivo studies showed that the extracts expedites the acute wound repair by formation of crust, wound closure and improves the blood perfusion towards the wound area. Together, the leaves of M. indica can be used as excellent therapeutic agent for tissue repair and wound healing applications.


Assuntos
Mangifera , Espectrometria de Massas em Tandem , Camundongos , Animais , Extratos Vegetais/farmacologia , Cromatografia Líquida , Diferenciação Celular
9.
Nat Prod Res ; : 1-8, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36691946

RESUMO

Lupeol is one of the most important metabolite in the class of terpenoids and possess excellent anticancer, anti-inflammatory, anti-diabetic activities etc. In the present study, the different thiazoles and oxazoles bearing lupeol derivatives were prepared to enhance their biological activity. Initially, the in vitro cytotoxic activity results showed that the synthesized lupeol derivatives (9a-9j and 10a-10e) showed significant activity against various cancer cells and the compounds 9h and 10b exhibited excellent activity against CAL27 cells. Further, these compounds 9h and 10b arrest the cell cycle at S phase and induce the late apoptosis in CAL27 cells by downregulating the BcL2 and vimentin expression and upregulating the Bax gene expression. Moreover, the lupeol derivatives showed dose-dependent anti-inflammatory activity by inhibiting the secretion of IL-6 cytokines in LPS-induced Raw 264.7 cells. Together, these results clearly indicated that the thiazoles and oxazoles bearing lupeol derivatives can used as chemotherapeutic drugs against cancer and inflammatory diseases.

10.
Nat Prod Res ; : 1-7, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37812197

RESUMO

(+)-Usnic acid (UA), a natural dibenzofuran derivative, abundantly produced by lichens and possess wide number of biomedical applications including antibacterial, anti-inflammatory, anti-oxidant and anticancer activities. In the present study, as series of usnic acid derivatives (3a-3i) were synthesised using Mannich reaction assessed for their antioxidant, α-glucosidase, and anticancer activities. The in vitro antioxidant activity showed that compound 3d displayed potent antioxidant activity by scavenging the activities of DPPH and ABTS+. The compounds 3d and 3e showed potent cytotoxic activity against HepG2 cancer cells by arresting the cell cycle at S phase and regulating the Bax/BcL2 expression and subsequently induce the apoptosis. Overall, the results clearly indicated that (+)-usnic acid derivatives bearing secondary amines are useful scaffolds for the development of drug candidates for treatment of oxidative stress mediated cancer and metabolic disorders.

11.
Life Sci ; 309: 121022, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36206836

RESUMO

In the present study, the wurtzite (WZ) type of zinc oxide (ZnO) nanoparticles were synthesized and functionalized with quercetin (ZnO@Quercetin) for the treatment of ovarian cancer. Initially, the chemical synthesis of ZnO nanoparticles was confirmed with DRS UV-vis spectroscopy and the bandgap of the ZnO revealed that the WZ type of nanoparticles. The electron microscopy analysis showed the hexagonal shape, monocrystalline nature of nanoparticles with an average size of 20-25 nm and the SAED pattern showed the interplanar planes for WZ type nanoparticles. XRD analysis revealed the presence of strong peaks corresponding to ZnO nanoparticles and the Raman spectroscopic analysis showed the characteristic peaks at E2 (high) and E1 vibrational mode for WZ type of ZnO nanoparticles. The in vitro cytotoxic activity of ZnO@Quercetin nanoparticles showed the excellent activity by generating intercellular oxidative stress and depolarization of mitochondrial membrane potential against human ovarian cancer cells. The dual-staining assay showed that the ZnO@Quercetin induces late apoptosis through activation of the intrinsic apoptosis signaling pathway in PA-1 cells. Together, the present study indicates the ZnO@Quercetin nanoparticles can be used for the treatment of human metastatic ovarian cancer.


Assuntos
Nanopartículas Metálicas , Neoplasias Ovarianas , Óxido de Zinco , Humanos , Feminino , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Quercetina/farmacologia , Apoptose , Neoplasias Ovarianas/tratamento farmacológico , Transdução de Sinais , Nanopartículas Metálicas/química
12.
Front Cell Infect Microbiol ; 12: 794338, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663469

RESUMO

The present study aimed to isolate and identify potential drugs from marine actinomycete Nocardiopsis exhalans and screen them for biomedical applications. The cell-free culture of N. exhalans was extracted with ethyl acetate and the solvent extract showed six fractions in thin-layer chromatography. The fractions were subjected to column chromatography for purification and evaluated for activity against human clinical pathogens. Fraction 4 showed significant activity and was identified as N-(2-hydroxyphenyl)-2-phenazinamine (NHP) using spectral analyses. Further, NHP showed excellent biofilm inhibitory activity against human clinical pathogens Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The in vitro antioxidant activity confirmed that NHP is scavenging the oxidative stress-enhancing molecules. The anti-proliferative activity of NHP against human breast cancer cells showed significant activity at 300 µg/ml and less cytotoxic activity against normal cells. Additionally, the toxicity assessment against zebrafish revealed that NHP does not cause any toxicity in the important organs. The results highlight N. exhalans as a promising candidate for the development of antibiotics with potential therapeutic applications.


Assuntos
Anti-Infecciosos , Nocardia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/toxicidade , Antioxidantes/farmacologia , Biofilmes , Escherichia coli , Testes de Sensibilidade Microbiana , Nocardiopsis , Peixe-Zebra
13.
Food Funct ; 13(24): 13002-13013, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36449013

RESUMO

Investigation of phytochemicals and bioactive molecules is tremendously vital for the applications of new plant resources in chemistry, food, and medicine. In this study, the chemical profiling of sap of Acer mono (SAM), a Korean syrup known for its anti-osteoporosis effect, was performed using UPLC-ESI-Q-TOF-MSE analysis. A total of 23 compounds were identified based on the mass and fragmentation characteristics and most of the compounds have significant biomedical applications. The in vitro antioxidant assessment of SAM indicated excellent activity by scavenging DPPH and ABTS-free radicals and were found to be 23.35 mg mL-1 and 29.33 mg mL-1, respectively, as IC50 concentrations. As well, the in vitro proliferation effect of the SAM was assessed against mouse MC3T3-E1 cells, and the results showed that the SAM enhanced the proliferation of the cells, and 12.5 mg mL-1 and 25 mg mL-1 of SAM were selected for osteogenic differentiation. The morphological analysis clearly evidenced the SAM enhanced the osteogenic activity in MC3T3-E1 cells by the increased deposition of extracellular calcium and nodule formation. Moreover, the qRT-PCR analysis confirmed the increased expression of osteoblast marker gene expression including ALP, osteocalcin, osteopontin, collagen1α1, Runx2, and osterix in SAM-treated MC3T3-E1 cells. Together, these results suggest that SAM possesses osteogenic effects and can be used for bone regeneration and bone loss-associated diseases such as osteoporosis.


Assuntos
Acer , Osteoblastos , Osteoporose , Extratos Vegetais , Animais , Camundongos , Acer/química , Diferenciação Celular , Osteoblastos/efeitos dos fármacos , Osteocalcina/metabolismo , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Células 3T3 , Metabolômica
14.
RSC Med Chem ; 13(8): 978-985, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36092140

RESUMO

In an attempt to develop natural product-based anticancer agents, a series of novel piperazine-linked bergenin heterocyclic hybrids bearing arylthiazolyl (5a-e), benzothiazolyl (10a-i), and arylsulfonyl (13a-o) were synthesized using the classical Mannich reaction and evaluated for their anticancer activity. All the synthesized derivatives were assessed for in vitro cytotoxic activity against a panel of human cancer and normal cell lines and the results showed that most of the compounds exhibited significant cytotoxic activity against cancer cells and mild cytotoxicity against normal cells. In particular, the compounds 5a, 5c, 10f, and 13o showed potent cytotoxic activity against tongue and oral cancer cell lines compared to the parent compound (<100 µM). Considering the efficacy, the compounds 5a, 5c, 10f, and 13o were subjected to cell cycle analysis and the results indicated that the compounds mitigated the cell cycle progression at the G0/G1 phase in the tongue and oral cancer cell lines. Subsequently, the annexin V/PI staining assay demonstrated that the compounds 5a, 5c, 10f, and 13o induced early and late apoptosis against tongue cancer and necrosis against oral cancer. Further, gene expression analysis revealed that 5a, 5c, and 13o treatment regulated the BAX and BcL-2 expression and also the selected compounds significantly reduced the expression level of vimentin, oct-4, and nanog. In addition, molecular docking studies revealed that the selected derivatives have strong binding energy with the BcL2 protein and downregulates the expression. Taken together, the study results implied that these compounds are promising anticancer candidates by modulating the epithelial to mesenchymal transition axis and could be considered for further development of novel anticancer drugs.

15.
Fitoterapia ; 161: 105246, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35760229

RESUMO

A series of novel nimbolide derivatives bearing various substitutions on 28th position was designed and synthesized using Sonogashira (2a-2p) and Glaser coupling (3a-3e) reactions. The synthesized derivatives were assessed for in vitro cytotoxic activity against four different human cancer cell lines (A549 cells, MCF-7 cells, MDA-MB-231 cells, and HCT15 cells) and normal cell line (HEK cells) using MTT assay. Among the screened derivatives, the compound 3a showed potent activity against A549 cells with IC50 value of 0.23 µM as comparing with parent molecule 1 (1.48 µM) and the standard drug doxorubicin (0.82 µM). As well, the flow cytometry analysis confirmed that the compounds 1 and 3a arrest the cell cycle progress at S phase and induce the early apoptosis in the lung cancer. The qRT-PCR analysis revealed that the compounds 1 and 3a downregulate the BcL2 expression and upregulates the Bax gene expression level in A549 cells. The strong binding affinity of the compounds 1 and 3a with BcL2 was also confirmed using molecular docking analysis. Together, the results suggested that the compound 3a is a promising anticancer agent against lung cancer is deserved for further investigation.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Alcinos , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Limoninas , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Relação Estrutura-Atividade
16.
Food Res Int ; 157: 111394, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35761649

RESUMO

Marine seaweeds are predominant for nutraceuticals and have been food source since ancient times and are currently being used in Chinese medicines and Japanese traditional medicines. In the present study, the chemical profile analysis of Halimeda gracilis was performed using UPLC-ESI-Q-TOF-MSE analysis and assessed for its anticancer activity. A cursory investigation of the total ion chromatograms of the both methanol (MHG) and ethyl acetate (EAHG) of H. gracilis extracts reveals that both extracts have different kind of metabolites including phenols and its derivatives, diterpenes, cinnamic acids derivatives etc. The in vitro anticancer activity of EAHG and MHG exhibiting significant activity and induced apoptosis against skin cancer cells by generating excessive ROS, damaging the mitochondrial membrane and nuclear components. Further, the western blot analysis showed that the EAHG and MHG downregulates the oncoproteins PI3K, AKT, p-AKT, and BcL2 and upregulates the apoptotic proteins Bax, Cyto C, p21, p53, Caspase 9 and Caspase 3. To best of our knowledge, this is the first report which implies the UPLC-ESI-Q-TOF-MSE based chemical profiling of H. gracilis and can be used for the treatment of cancer.


Assuntos
Medicamentos de Ervas Chinesas , Alga Marinha , Apoptose , Cromatografia Líquida de Alta Pressão , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Alga Marinha/química , Transdução de Sinais
17.
Nat Prod Res ; : 1-7, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083601

RESUMO

In continuation of our research program aimed at the development of new natural product-based anticancer agents, a series of lupeol derivatives (5a-5k and 6a-6i) were prepared with the introduction of aryl functionalities and amino acids at C-3 position. All the synthesised derivatives were assessed for in vitro anticancer activity against four human cancer cell lines using MTT assay. Interestingly, the compounds 5j, 5k, and 6 g showed potent activity against MCF7 cells as compared with the parent compound. Further, the flowcytometry analysis revealed that the 5j,5k, and 6 g arrest the cells at the G2/M phase and induce the early apoptosis in MCF7 cells. In addition, the selected compounds inhibit the BcL2 expression and increase the Bax protein expression in MCF7 cells. Overall, these results indicated that the lupeol derivatives could serve as a promising launch point for the development of anticancer agents.

18.
J Agric Food Chem ; 69(12): 3776-3786, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33730852

RESUMO

In the present study, we comparatively analyzed the transcriptomic profiling of fibroblasts derived from two different muscles, biceps femoris and longissimus dorsi with significant difference in the meat quality and tenderness. EBSeq algorithm was applied to analyze the data, and genes were considered to be significantly differentially expressed if the false discovery rate value was <0.05, the P value was <0.01, and the fold change was >0.585. The results revealed that 253 genes were differentially expressed genes (DEGs) (170 genes were upregulated, and 83 were downregulated) and more than 100 DEGs were probably associated with intramuscular fat deposition, tenderness, and toughness, which are driving the meat quality and were involved in biological processes such as collagen synthesis, cell differentiation, and muscle tissue and fiber development; molecular functions such as chemokine activity and collagen activity; cellular components such as cytoplasm and myofibril; and pathways such as collagen signaling and metabolic pathways. A gene-act network and a co-expression network revealed the close relationship between intramuscular fat deposition and meat tenderness. The expressions of 20 DEGs were validated by real-time PCR, and the results suggested that the DEGs are correlated with RNA-seq data and play crucial roles in muscle growth, development processes, toughness, and tenderness of the meat. Together, the genome-wide transcriptome analysis revealed that various genes are responsible for toughness and tenderness variance in the difference muscles of beef.


Assuntos
Músculo Esquelético , Transcriptoma , Animais , Bovinos/genética , Fibroblastos , Perfilação da Expressão Gênica , Carne
19.
Life (Basel) ; 11(4)2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33923931

RESUMO

Increased levels of type I (T1) interferon (IFN)-inducible POP3 protein in myeloid cells inhibit activation of the AIM2 inflammasome and production of IL-1ß and IL-18 proinflammatory cytokines. The AIM2 mRNA levels were significantly higher in benign prostate hyperplasia (BPH) than the normal prostate. Further, human normal prostate epithelial cells (PrECs), upon becoming senescent, activated an inflammasome. Because in aging related BPH senescent PrECs accumulate, we investigated the role of POP3 and AIM2 proteins in pre-senescent and senescent PrECs. Here we report that the basal levels of the POP3 mRNA and protein were lower in senescent (versus young or old) PrECs that exhibited activation of the T1 IFN response. Further, treatment of PrECs and a BPH cell line (BPH-1) that expresses the androgen receptor (AR) with the male sex hormone dihydrotestosterone (DHT) increased the basal levels of POP3 mRNA and protein, but not AIM2, and inhibited activation of the AIM2 inflammasome. Of interest, a stable knockdown of POP3 protein expression in the BPH-1 cell line increased cytosolic DNA-induced activation of AIM2 inflammasome. These observations suggest a potential role of POP3 protein in aging-related prostatic inflammation.

20.
J Hazard Mater ; 416: 126209, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492970

RESUMO

In this present study, spherical shaped zinc ferrite (Zn/Fe2O4) was prepared as uniformly sized (65 ± 0.5 nm) nanoparticles with band gap (2.00 eV) in a visible light regime and employed for the photocatalytic degradation of carbamazepine (CBZ). The doping of Zn decreased the band gap (from 2.00 to 1.98 eV) and enhanced the absorption of visible light. Zinc doping also induced effective separation of photogenerated carriers and subsequent charge migration to the surface of the Zn/Fe2O4 nanoparticle. On account of the advantages of the material, a high removal efficiency (~ 100%) of CBZ through photocatalytic degradation was achieved. Kinetics of CBZ degradation follows a pseudo first-order with the rate constant 0.0367 min-1. In-vitro and in-vivo toxicity of the nanoparticles were examined promoting the environmental implications.


Assuntos
Carbamazepina , Zinco , Carbamazepina/toxicidade , Catálise , Compostos Férricos , Luz , Zinco/toxicidade
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