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1.
Drug Dev Res ; 85(4): e22215, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837718

RESUMO

Breast cancer is the second most frequent cancer among women. Out of various subtypes, triple-negative breast cancers (TNBCs) account for 15% of breast cancers and exhibit more aggressive characteristics as well as a worse prognosis due to their proclivity for metastatic progression and limited therapeutic strategies. It has been demonstrated that AMP-activated protein kinase (AMPK) has context-specific protumorigenic implications in breast cancer cells. A set of glucosyltriazole amphiphiles, consisting of acetylated (9a-h) and unmodified sugar hydroxyl groups (10a-h), were synthesized and subjected to in vitro biological evaluation. Among them, 9h exhibited significant anticancer activity against MDA-MB-231, MCF-7, and 4T1 cell lines with IC50 values of 12.5, 15, and 12.55 µM, respectively. Further, compound 9h was evaluated for apoptosis and cell cycle analysis in in vitro models (using breast cancer cells) and antitumour activity in an in vivo model (orthotopic mouse model using 4T1 cells). Annexin-V assay results revealed that treatment with 9h caused 34% and 28% cell death at a concentration of 15 or 7.5 µM, respectively, while cell cycle analysis demonstrated that 9h arrested the cells at the G2/M or G1 phase in MCF-7, MDA-MB-231 and 4T1 cells, respectively. Further, in vivo, investigation showed that compound 9h exhibited equipotent as doxorubicin at 7.5 mg/kg, and superior efficacy than doxorubicin at 15 mg/kg. The mechanistic approach revealed that 9h showed potent anticancer activity in an in vivo orthotopic model (4T1 cells) partly by suppressing the AMPK activation. Therefore, modulating the AMPK activation could be a probable approach for targeting breast cancer and mitigating cancer progression.


Assuntos
Proteínas Quinases Ativadas por AMP , Antineoplásicos , Apoptose , Transdução de Sinais , Triazóis , Humanos , Feminino , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Triazóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Camundongos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Camundongos Endogâmicos BALB C , Células MCF-7 , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Indian J Exp Biol ; 51(5): 393-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23821828

RESUMO

Silver nanoparticles is known to have antimicrobial affects. Cyanobacteria isolates from muthupet mangrove includes Aphanothece sp, Oscillatoria sp, Microcoleus sp, Aphanocapsa sp, Phormidium sp, Lyngbya sp, Gleocapsa sp, Synechococcus sp, Spirulina sp with were set in compliance with their cellular mechanism of nano silver creation, and were investigated by UV-VIS spectrophotometer, Energy-dispersive X-ray (EDX) and scanning electron microscopy (SEM). Silver nanoparticles were spherical shaped well distributed without aggregation in solution with an average size of about 40- 80 nm. Synthesised nano silver had antibacterial production on various organisms that provoked various diseases in humans. The cellular metabolites of Microcoleus sp. only created nano silver and it enhanced the antibacterial activity against test pathogenic bacteria from MTCC (Proteus vulgaris, Salmonella typhi, Vibrio cholera, Streptococcus sp., Bacillus subtilis, Staphylococcus aureus, Escherichia coli.) The antimicrobial assay was performed using 0.001 M concentration of nano silver in well diffusion method with positive control of appropriate standard antibiotic discs Cephotaxime, Ampicillin, Tetracyclin, Cephalexin etc. Synthesised silver nanoparticles acted as an effective antimicrobial agent and proved as an alternative for the development of new antimicrobial agents to combat the problem of resistance.


Assuntos
Antibacterianos/farmacologia , Nanopartículas Metálicas , Microalgas/fisiologia , Prata/metabolismo , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Espectrometria por Raios X
3.
Artigo em Inglês | MEDLINE | ID: mdl-23711394

RESUMO

The biosynthesis of silver nanoparticles and its antimicrobial property was studied using bacteria isolated from Spirulina products. Isolated bacteria were identified as Bacillus sp. MSK 1 (JX495945), Staphylococcus sp. MSK 2 (JX495946), Bacillus sp. MSK 3 (JX495947) and Brevundimonas sp. MSK 4 (JX495948). Silver nanoparticles (AgNPs) were synthesized using bacterial culture filtrate with AgNO3. The initial syntheses of Ag nanoparticles were characterized by UV-vis spectrophotometer (by measuring the color change to intense brown). Fourier Transform Infrared Spectroscopy (FTIR) study showed evidence that proteins are possible reducing agents and Energy-dispersive X-ray (EDX) study showing the metal silver as major signal. The structure of AgNPs was determined by Scanning electron microscopy (SEM) and X-ray diffraction (XRD). Synthesized Ag nanoparticles with an average size of 40-65 nm have antimicrobial property against human pathogens like Proteus vulgaris, Salmonella typhi, Vibrio cholera, Streptococcus sp., Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. Among the isolates Brevundimonas sp. MSK 4 alone showed good activity in both synthesis of AgNPs and antimicrobial activity. This work demonstrates the possible use of biological synthesized silver nanoparticles to combat the drug resistant problem.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Bactérias/metabolismo , Nanopartículas Metálicas/química , Microalgas/microbiologia , Prata/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Carbono/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Spirulina/efeitos dos fármacos
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