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1.
Environ Pollut ; 348: 123745, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38499169

RESUMO

The article discusses the removal of methylene blue (MB) dye, a common cationic dye used in the textile industry, from aqueous solutions through an adsorption process. The use of porous components as adsorbents are shown to facilitate complete separation after the process is completed. The substrate was synthesized by connecting zinc copper ferrite (ZnCuFe2O4), polyethyleneimine (PEI), and Graphene Oxide (GO) sheets to MCM-48, which is a mesoporous material. The surface of MCM-48 was modified using CPTMS, which created an O-Si-Cl bridge, thereby improving the adsorption rate. The substrate was shown to have suitable sites for electrostatic interactions and creating hydrogen bonds with MB. The adsorption process from the Freundlich isotherm (R2 = 0.9224) and the pseudo-second-order diagram (R2 = 0.9927) demonstrates the adsorption of several layers of dye on the heterogeneous surface of the substrate. The synthesized substrate was also shown to have good bactericidal activity against E. coli and S. aureus bacterial strain. Furthermore, the substrate maintained its initial ability to adsorb MB dye for four consecutive cycles. The research resulted that ZnCuFe2O4@MCM-48/PEI-GO substrate has the potential for efficient and economical removal of MB dye from aqueous solutions (R = 88.82%) (qmax = 294.1176 mg. g-1), making it a promising solution for the disposal of harmful industrial waste.


Assuntos
Compostos Férricos , Grafite , Nanopartículas , Poluentes Químicos da Água , Purificação da Água , Dióxido de Silício , Polietilenoimina , Cobre , Zinco , Escherichia coli , Porosidade , Staphylococcus aureus , Antibacterianos/farmacologia , Azul de Metileno/química , Purificação da Água/métodos , Adsorção , Cinética , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio
2.
Int J Biol Macromol ; 263(Pt 1): 130694, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458284

RESUMO

Zinc oxide (ZnO) has attracted a substantial interest in cancer research owing to their promising utility in cancer imaging and therapy. This study aimed to synthesized ZnO nanoflowers coated with albumin to actively target and the inhibit skin melanoma cells. We synthesized bovine serum albumin (BSA)-coated ZnO nanoflowers (BSA@ZnO NFs) and evaluated it's in vitro and in vivo therapeutic efficacy for skin cancer cells. BSA@ZnO NFs were prepared via single-step reduction method in the presence of plant extract (Heliotropium indicum) act as a capping agent, and further the successful fabrication was established by various physico-chemical characterizations, such as scanning electron microscopy (SEM), Fourier transform infra-red (FT-IR) spectroscopy, and x-rays diffraction (XRD) analysis. The fabricated BSA@ZnO NFs appeared flower like with multiple cone-shaped wings and average hydration size of 220.8 ± 12.6 nm. Further, BSA@ZnO NFs showed enhanced cellular uptake and cytocidal effects against skin cancer cells by inhibiting their growth via oxidative stress compared uncoated ZnO NFs. Moreover, BSA@ZnO NFs showed enhance biosafety, blood circulation time, tumor accumulation and in vivo tumor growth inhibition compared to ZnO NFs. In short, our findings suggesting BSA@ZnO NFs as a promising candidate for various types of cancer treatment along with chemotherapy.


Assuntos
Melanoma , Nanopartículas Metálicas , Neoplasias Cutâneas , Óxido de Zinco , Animais , Humanos , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Espectroscopia de Infravermelho com Transformada de Fourier , Melanoma/tratamento farmacológico , Soroalbumina Bovina/química , Neoplasias Cutâneas/tratamento farmacológico , Estresse Oxidativo , Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Extratos Vegetais/química
3.
Int J Pharm X ; 7: 100238, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38511068

RESUMO

The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.

4.
Curr Mol Pharmacol ; 17: e18761429269383, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389415

RESUMO

BACKGROUND: Lung cancer (LC) incidence is rising globally and is reflected as a leading cause of cancer-associated deaths. Lung cancer leads to multistage carcinogenesis with gradually increasing genetic and epigenetic changes. AIMS: Sanguinarine (sang) mediated the anticancer effect in LCC lines by involving the stimulation of reactive oxygen species (ROS), impeding Bcl2, and enhancing Bax and other apoptosis-associated protein Caspase-3, -9, and -PARP, subsequently inhibiting the LC invasion and migration. OBJECTIVE: This study was conducted to investigate the apoptotic rate and mechanism of Sang in human LC cells (LCC) H522 and H1299. METHODS: MTT assay to determine the IC50, cell morphology, and colony formation assay were carried out to show the sanguinarine effect on the LC cell line. Moreover, scratch assay and transwell assay were performed to check the migration. Western blotting and qPCR were done to show its effects on targeted proteins and genes. ELISA was performed to show the VEGF effect after Sanguinarine treatment. Immunofluorescence was done to check the interlocution of the targeted protein. RESULTS: Sang significantly inhibited the growth of LCC lines in both time- and dose-dependent fashions. Flow cytometry examination and Annexin-V labeling determined that Sang increased the apoptotic cell percentage. H522 and H1299 LCC lines treated with Sang showed distinctive characteristics of apoptosis, including morphological changes and DNA fragmentation. CONCLUSION: Sang exhibited anticancer potential in LCC lines and could induce apoptosis and impede the invasion and migration of LCC, emerging as a promising anticancer natural agent in lung cancer management.


Assuntos
Antineoplásicos , Isoquinolinas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Apoptose , Benzofenantridinas/farmacologia , Benzofenantridinas/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Estresse Oxidativo
5.
J Adv Res ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38320729

RESUMO

BACKGROUND: The emergence of carbon dots (CDs) as anticancer agents had sparked a transformation in cancer research and treatment strategies. These fluorescent CDs, initially introduced in the early 2000 s, possess exceptional biocompatibility, tunable fluorescence, and surface modification capabilities, positioning them as promising tools in biomedical applications. AIM OF REVIEW: The review encapsulates the transformative trajectory of green CDs as future anticancer nanomedicine, poised to redefine the strategies employed in the ongoing fight against cancer. KEY SCIENTIFIC CONCEPTS OF REVIEW: The versatility of CDs was rooted in their various synthesis approaches and sustainable strategies, enabling their adaptability for diverse therapeutic uses. In vitro studies had showcased CDs' selective cytotoxicity against cancer cells while sparing healthy counterparts, forming the basis for targeted therapeutic potential. This selectivity had been attributed to the reactive oxygen species (ROS) generation, which opened avenues for targeted interventions. The role of CDs in combination therapies, synergizing with chemotherapy, radiotherapy, and targeted approaches was then investigated to heighten their anticancer efficacy. Notably, in vivo studies highlight CDs' remarkable biocompatibility and minimal side effects, endorsing their translational promise. Integration with conventional cancer treatments such as chemotherapy, radiotherapy, and immunotherapy amplified the versatility and effectiveness of CDs. The exploration of CDs' applications in photo-induced treatments further solidified their significance, positioning them as photosensitizers (PS) in photodynamic therapy (PDT) and photothermal agents (PA) in photothermal therapy (PTT). In PDT, CDs triggered the generation of ROS upon light exposure, facilitating cancer cell elimination, while in PTT, they induced localized hyperthermia within cancer cells, enhancing therapeutic outcomes. In vitro and in vivo investigations validated CDs' efficacy in PDT and PTT, affirming their potential for integration into combination therapies. Looking ahead, the future of CDs in anticancer treatment encompasses bioavailability, biocompatibility, synergistic treatments, tumor targeting, artificial intelligence (AI) and robotics integration, personalized medicine, and clinical translation. This transformative odyssey of CDs as future anticancer agents is poised to redefine the paradigm of cancer treatment strategies.

6.
Bioorg Chem ; 145: 107228, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38422592

RESUMO

In this work, readily achievable synthetic pathways were utilized for construction of a library of N/S analogues based on the pyrazolopyrimidine scaffold with terminal alkyl or aryl fragments. Subsequently, we evaluated the anticancer effects of these novel analogs against the proliferation of various cancer cell lines, including breast, colon, and liver lines. The results were striking, most of the tested molecules exhibited strong and selective cytotoxic activity against the MDA-MB-231 cancer cell line; IC50 1.13 µM. Structure-activity relationship (SAR) analysis revealed that N-substituted derivatives generally enhanced the cytotoxic effect, particularly with aliphatic side chains that facilitated favorable target interactions. We also investigated apoptosis, DNA fragmentation, invasion assay, and anti-migration effects, and discussed their underlying molecular mechanisms for the most active compound 7c. We demonstrated that 7c N-propyl analogue could inhibit MDA-MB-231 TNBC cell proliferation by inducing apoptosis through the regulation of vital proteins, namely c-Src, p53, and Bax. In addition, our results also revealed the potential of these compounds against tumor metastasis by downregulating the invasion and migration modes. Moreover, the in vitro inhibitory effect of active analogs against c-Src kinase was studied and proved that might be the main cause of their antiproliferative effect. Overall, these compelling results point towards the therapeutic potential of these derivatives, particularly those with N-substitution as promising candidates for the treatment of TNBC type of breast cancer.


Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteína Tirosina Quinase CSK/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Quinases da Família src , Relação Estrutura-Atividade , Pirimidinas/química , Pirimidinas/farmacologia , Pirazóis/química , Pirazóis/farmacologia
7.
PLoS One ; 19(1): e0296010, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38266021

RESUMO

The present study explores the epidermal growth factor receptor (EGFR) tyrosine kinase inhibition efficacy of secondary metabolites in Trichoderma spp. through molecular docking, molecular dynamics (MD) simulation and MM-PBSA approach. The result of molecular docking confirmed that out of 200 metabolites screened, three metabolites such as Harzianelactone A, Pretrichodermamide G and Aspochalasin M, potentially bound with the active binding site of EGFR tyrosine kinase domain(PDB ID: 1M17) with a threshold docking score of ≤- 9.0 kcal/mol when compared with the standard EGFR inhibitor (Erlotinib). The MD simulation was run to investigate the potential for stable complex formation in EGFR tyrosine kinase domain-unbound/lead metabolite (Aspochalasin M)-bound/standard inhibitor (Erlotinib)-bound complex. The MD simulation analysis at 100 ns revealed that Aspochalasin M formed the stable complex with EGFR. Besides, the in silico predication of pharmacokinetic properties further confirmed that Aspochalasin M qualified the drug-likeness rules with no harmful side effects (viz., hERG toxicity, hepatotoxicity and skin sensitization), non-mutagenicity and favourable logBB value. Moreover, the BOILED-Egg model predicted that Aspochalasin M showed a higher gastrointestinal absorption with improved bioavailability when administered orally and removed from the central nervous system (CNS). The results of the computational studies concluded that Aspochalasin M possessed significant efficacy in binding EGFR's active sites compared to the known standard inhibitor (Erlotinib). Therefore, Aspochalasin M can be used as a possible anticancer drug candidate and further in vitro and in vivo experimental validation of Aspochalasin M of Trichoderma spp. are required to determine its anticancer potential.


Assuntos
Trichoderma , Cloridrato de Erlotinib , Simulação de Acoplamento Molecular , Receptores ErbB
8.
Colloids Surf B Biointerfaces ; 234: 113762, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244483

RESUMO

Gastric ulcers are worrying, and their worsening conditions may result in bleeding in the internal lining of the stomach. The problem is annoying, and both patients and professionals are still not satisfied with the available treatment options. Hesperidin, a flavonoid molecule with potent anti-inflammatory and antioxidant effects, can work like witchcraft to repair gastric ulcers and preserve the stomach lining. Here, we employed a strategy that involved covering the surface of the nano-lipid carriers (NLCs) with sericin before encasing the hesperidin within (Se-He-NLC). Sericin, a biodegradable polymer increases the muco-adhesion with stomach lining and deployment of hesperidin in controlled manner. Se-He-NLCs were physico-chemically characterized for drug loading, encapsulation, particle size, morphology, drug release, chemical stability, and chemical bonding. The nanocarriers showed first order drug release in a controlled manner. Se-He-NLCs showed better in vitro permeation and ex vivo mucoadhesion, thereby by promoting the in vivo bioavailability. Se-He-NLCs also promoted the reduced glutathione (GSH) and glutathione-S-transferase (GST) levels by 2.24- and 1.61-folds, respectively in the stomach lining, and also the regulation of superoxide dismutase (SOD) and catalase (CAT) activities parallel to the control group. In addition, tissues lipid hydroperoxides (LOOH) and myeloperoxidase (MPO) activity were reduced significantly with Se-He-NLCs administration. Se-He-NLC therapy of stomach ulcers in vivo demonstrated better binding ratio and ulcer healing potential. This approach reveals huge capacity for delivering therapies to treat gastric ulcers based on the clinical significance of sericin coated hesperidin nanocarriers in gastric ulcer treatment.


Assuntos
Hesperidina , Nanopartículas , Sericinas , Úlcera Gástrica , Humanos , Ratos , Animais , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Hesperidina/farmacologia , Ratos Wistar , Antioxidantes/metabolismo , Superóxido Dismutase/metabolismo
9.
Curr Protein Pept Sci ; 25(3): 244-255, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37909437

RESUMO

Eph receptors and their Eph receptor-interacting (ephrin) ligands comprise a vital cell communication system with several functions. In cancer cells, there was evidence of bilateral Eph receptor signaling with both tumor-suppressing and tumor-promoting actions. As a member of the Eph receptor family, EphB4 has been linked to tumor angiogenesis, growth, and metastasis, which makes it a viable and desirable target for drug development in therapeutic applications. Many investigations have been conducted over the last decade to elucidate the structure and function of EphB4 in association with its ligand ephrinB2 for its involvement in tumorigenesis. Although several EphB4-targeting drugs have been investigated, and some selective inhibitors have been evaluated in clinical trials. This article addresses the structure and function of the EphB4 receptor, analyses its possibility as an anticancer therapeutic target, and summarises knowledge of EphB4 kinase inhibitors. To summarise, EphB4 is a difficult but potential treatment option for cancers.


Assuntos
Neoplasias , Receptor EphA1 , Humanos , Efrina-B2/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Receptores da Família Eph , Receptor EphB4/genética , Receptor EphB4/metabolismo
10.
Int J Biol Macromol ; 258(Pt 1): 128839, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38134998

RESUMO

In this study, we aim to unveil the potential of itaconyl chondroitin sulfate nanogel (ICSNG) in tackling chronic kidney diseases triggered by the administration of CDDP and doxorubicin (Adriamycin, ADR). To that end, the new drug delivery system (ICSNG) was initially prepared, characterized, and loaded with the target drugs. Thereafter, the in-vivo studies were performed using five equally divided groups of 100 male Sprague-Dawley (SD) rats. Biochemical evaluation and immunohistochemistry studies have revealed the renal toxicity and the ameliorative effects of ICSNG on renal function. When ICSNG-based treatments were contrasted with the CDDP and ADR infected groups, they significantly increased paraoxonase-1 (PON-1), superoxide dismutase (SOD), catalase (CAT) and albumin activity and significantly decreased nitric oxide (NO), tumor necrosis factor alpha (TNF-α), creatinine, urea, and cyclooxygenase-2 (COX-2) activity (p < 0.001). The findings of the current study imply that ICSNG may be able to lessen renal inflammation and damage in chronic kidney disorders brought on by the administration of CDDP and ADR. Interestingly, according to the estimated selectivity indices, the ICSNG-encapsulated drugs have demonstrated superior selectivity for cancer MCF-7 cells, over healthy HSF cells, in comparison to the bare drugs.


Assuntos
Cisplatino , Rim , Polietilenoglicóis , Polietilenoimina , Ratos , Masculino , Animais , Cisplatino/farmacologia , Sulfatos de Condroitina/farmacologia , Nanogéis , Ratos Sprague-Dawley , Antioxidantes/farmacologia , Doxorrubicina/farmacologia , Estresse Oxidativo , Creatinina/metabolismo
11.
Saudi Pharm J ; 31(12): 101839, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37965489

RESUMO

Itraconazole (ITZ) is a renowned antifungal medication, however its therapeutic efficacy is limited by low solubility and oral bioavailability. The current research work attempted to augment the oral bioavailability of ITZ by incorporating into self-emulsifying micelles (SEMCs). To fabricate the SEMCs, various preparation techniques including physical mixture, melt-emulsification, solvent evaporation and kneading, were opted by using different weight ratio of drug and solubilizers i.e. Gelucire-50/13 or Gelucire-44/14 and characterized both in vitro and in vivo. The prepared SEMCs were found to be in the size range from 63.4 ± 5.2 to 284.2 ± 19.5 nm with surface charges ranging from -16 ± 1.2 to -27 ± 2.0 mV. The drug solubility was improved to a reasonable extent with all investigated formulations, however, SEMCs in group 6 prepared by kneading method (KMG6) using Gelucire-44/14: drug (10:1 presented 87.6 folds' increase (964.93 ± 2 µg/mL) compared to solubility of crystalline ITZ (11 ± 2 µg/mL) through kneading method. In addition, KMG6 SEMCs shows the fast drug release compared to other SEMCs. Further, KMG6 SEMCs also exhibited 5.12-fold higher relative intestinal serosal fluid absorption compared to crystalline ITZ. The pharmacokinetic parameters such Cmax, AUC and Tmax of KMG6 SEMCs significantly improved compared to crystalline ITZ. In conclusion, the manipulation of ITZ solubility, dissolution rate and absorption using SEMCs is a promising strategy for bioavailability enhancement.

12.
Biomed Pharmacother ; 168: 115757, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897972

RESUMO

Costunolide (COST) is a sesquiterpene lactone that belongs to the germacranolide group, and occurs mainly in Saussurea lappa Clarke. Although COST inhibits the proliferation and metastasis of cancer cells and induces their apoptosis, it suffers poor water solubility and cellular permeability. Therefore, this study aimed to enhance the anti-proliferative activity of COST in LS174T colon cancer cells through its inclusion in bilosomal nanoformulation (COST-BILs). The optimized BIL formula contained cholesterol and Span-85 in a molar ratio of 1:5 as well as bile salt at a molar concentration of 0.5 mM, with entrapment efficiency of 63.4 ± 3.59 % and particle size of 119.7 ± 3.63 nm. The optimized COST-BILs showed a potent cytotoxic effect against LS174T cells with an IC50 of 6.20 µM; meanwhile, raw COST had an IC50 of 15.78 µM. Safety and relative selectivity were confirmed in the normal human colonic epithelial cells (HCoEpC). Cell cycle analysis indicated that both raw COST and COST-BILs significantly increased the fraction of LS174T cells in the sub-G1 phase. This was accompanied by a significant enhancement of early, late, and total apoptosis, as indicated by annexin-V staining. In addition, COST-BILs exhibited more potent activity in up-regulating CASP3, TP53, and BAX, and in down-regulating the expression of BCL2 mRNA as compared to raw COST. Further, the prepared formula enhanced the release of cytochrome C as well as the generation of reactive oxygen species (ROS) and reduced the integrity of mitochondrial membranes. In conclusion, the loading of COST on BILs significantly enhances its pro-apoptotic activity in LS174T cells.


Assuntos
Antineoplásicos , Neoplasias do Colo , Nanopartículas , Sesquiterpenos , Humanos , Antineoplásicos/farmacologia , Sesquiterpenos/farmacologia , Apoptose , Neoplasias do Colo/tratamento farmacológico , Proliferação de Células
13.
Front Microbiol ; 14: 1227951, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37744917

RESUMO

Zinc oxide nanoparticles (ZnO-NPs) synthesized through biogenic methods have gained significant attention due to their unique properties and potential applications in various biological fields. Unlike chemical and physical approaches that may lead to environmental pollution, biogenic synthesis offers a greener alternative, minimizing hazardous environmental impacts. During biogenic synthesis, metabolites present in the biotic sources (like plants and microbes) serve as bio-reductants and bio-stabilizers. Among the biotic sources, microbes have emerged as a promising option for ZnO-NPs synthesis due to their numerous advantages, such as being environmentally friendly, non-toxic, biodegradable, and biocompatible. Various microbes like bacteria, actinomycetes, fungi, and yeast can be employed to synthesize ZnO-NPs. The synthesis can occur either intracellularly, within the microbial cells, or extracellularly, using proteins, enzymes, and other biomolecules secreted by the microbes. The main key advantage of biogenic synthesis is manipulating the reaction conditions to optimize the preferred shape and size of the ZnO-NPs. This control over the synthesis process allows tailoring the NPs for specific applications in various fields, including medicine, agriculture, environmental remediation, and more. Some potential applications include drug delivery systems, antibacterial agents, bioimaging, biosensors, and nano-fertilizers for improved crop growth. While the green synthesis of ZnO-NPs through microbes offers numerous benefits, it is essential to assess their toxicological effects, a critical aspect that requires thorough investigation to ensure their safe use in various applications. Overall, the presented review highlights the mechanism of biogenic synthesis of ZnO-NPs using microbes and their exploration of potential applications while emphasizing the importance of studying their toxicological effects to ensure a viable and environmentally friendly green strategy.

14.
Front Oncol ; 13: 1221275, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37706181

RESUMO

Breast cancer is a leading cause of mortality in women, and alternative therapies with fewer side effects are actively being explored. Breast cancer is a significant global health concern, and conventional treatments like radiotherapy and chemotherapy often have side effects. Medicinal plant extracts offer a promising avenue for the development of effective and safe anticancer therapies. Terminalia chebula, a plant known for its medicinal properties, was selected for investigation in this study. We aimed to assess the antiproliferative effects of TCF extract on breast cancer cells and explore the potential role of saccharopine, a phytochemical found in TCF, as an anticancer agent. MCF7 breast cancer cell lines were exposed to TCF extract, and cell viability and apoptosis assays were performed to evaluate the antiproliferative and apoptogenic effects. Molecular docking studies were conducted to assess the binding affinity of saccharopine with EGFRs. Molecular dynamics simulations and binding energy calculations were employed to analyze the stability of the EGFR-saccharopine complex. The TCF extract exhibited significant antiproliferative effects on MCF7 breast cancer cells and induced apoptosis in a dose-dependent manner. Molecular docking analysis revealed that saccharopine demonstrated a higher binding affinity with EGFR compared to the reference compound (17b-estradiol). The subsequent MDS simulations indicated stable binding patterns and conformation of the EGFR-saccharopine complex, suggesting a potential role in inhibiting EGFR-mediated signaling pathways. The investigation of Terminalia chebula fruit extract and its phytochemical saccharopine has revealed promising antiproliferative effects and a strong binding affinity with EGFR. These findings provide a foundation for future research aimed at isolating saccharopine and conducting in vivo studies to evaluate its potential as a targeted therapy for breast cancer. The development of novel anticancer agents from plant sources holds great promise in advancing the field of oncology and improving treatment outcomes for breast cancer patients.

15.
Pharmaceuticals (Basel) ; 16(7)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37513936

RESUMO

A series of novel enantiopure isoxazolidine derivatives were synthesized and evaluated for their anticancer activities against three human cancer cell lines such as human breast carcinoma (MCF-7), human lung adenocarcinoma (A-549), and human ovarian carcinoma (SKOV3) by employing MTT assay. The synthesized compounds were characterized by NMR and elemental analysis. Results revealed that all the synthesized compounds displayed significant inhibition towards the tested cell lines. Among them, 2g and 2f, which differ only by the presence of an ester group at the C-3 position and small EDG (methyl) at the C-5 position of the phenyl ring (2g), were the most active derivatives in attenuating the growth of the three cells in a dose-dependent manner. The IC50 for 2g were 17.7 ± 1 µM (MCF-7), 12.1 ± 1.1 µM (A-549), and 13.9 ± 0.7 µM (SKOV3), and for 2f were 9.7 ± 1.3µM (MCF-7), 9.7 ± 0.7µM (A-549), and 6.5 ± 0.9µM (SKOV3), respectively, which were comparable to the standard drug, doxorubicin. The enzymatic inhibition of 2f and 2g against EGFR afforded good inhibitory activity with IC50 of 0.298 ± 0.007 µM and 0.484 ± 0.01 µM, respectively, close to the positive control, Afatinib. Compound 2f arrested the cell cycle in the S phase in MCF-7 and SKOV3 cells, and in the G2/M phase in the A549 cell; however, 2g induced G0/G1 phase cell cycle arrest, and inhibited the progression of the three cancer cells, together with significant apoptotic effects. The docking study of compounds 2f and 2g into EGFR ATP-active site revealed that it fits nicely with good binding affinity. The pharmacokinetic and drug-likeness scores revealed notable lead-like properties. At 100 ns, the dynamic simulation investigation revealed high conformational stability in the EGFR binding cavity.

16.
Antibiotics (Basel) ; 12(7)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37508206

RESUMO

This study presents a green protocol for the fabrication of a multifunctional smart nanobiocomposite (NBC) (ZnO-PIACSB-TiO2) for secure antimicrobial and antibiofilm applications. First, shrimp shells were upgraded to a polyimidazolium amphiphilic chitosan Schiff base (PIACSB) through a series of physicochemical processes. After that, the PIACSB was used as an encapsulating and coating agent to manufacture a hybrid NBC in situ by co-encapsulating ZnONPs and TiO2NPs. The physicochemical and visual characteristics of the new NBC were investigated by spectral, microscopic, electrical, and thermal methods. The antimicrobial indices revealed that the newly synthesized, PIACSB-coated TiO2-ZnO nanocomposite is an exciting antibiotic due to its amazing antimicrobial activity (MIC/MBC→0.34/0.68 µg/mL, 0.20/0.40 µg/mL, and 0.15/0.30 µg/mL working against S. aureus, E. coli, and P. aeruginosa, respectively) and antifungal capabilities. Additionally, ZnO-PIACSB-TiO2 is a potential fighter of bacterial biofilms, with the results being superior to those of the positive control (Cipro), which worked against S. aureus (only 8.7% ± 1.9 biofilm growth), E. coli (only 1.4% ± 1.1 biofilm growth), and P. aeruginosa (only 0.85% ± 1.3 biofilm growth). Meanwhile, the NBC exhibits excellent biocompatibility, as evidenced by its IC50 values against both L929 and HSF (135 and 143 µg/mL), which are significantly higher than those of the MIC doses (0.24-24.85 µg/mL) that work against all tested microbes, as well as the uncoated nanocomposite (IC50 = 19.36 ± 2.04 and 23.48 ± 1.56 µg/mL). These findings imply that the new PIACSB-coated nanocomposite film may offer promising multifunctional food packaging additives to address the customer demand for safe, eco-friendly food products with outstanding antimicrobial and antibiofilm capabilities.

17.
Environ Res ; 234: 116523, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37422115

RESUMO

Plastic is now considered part and parcel of daily life due to its extensive usage. Microplastic (MP) pollution is becoming a growing worry and has been ranked as the second most critical scientific problem in the realm of ecology and the environment. Microplastics are smaller in size than the plastic and are more harmful to biotic and as well as abiotic environments. The toxicity of microplastic depends upon its shape and size and increases with an increase in its adsorption capacity and their toxicity. The reason behind their harmful nature is their small size and their large surface area-to-volume ratio. Microplastic can get inside fruits, vegetables, seeds, roots, culms, and leaves. Hence microplastic enters into the food chain. There are different entry points for microplastic to enter into the food chain. Such sources can include polluted food, beverages, spices, plastic toys, and household (packing, cooking, etc.). The concentration of microplastic in terrestrial environments is increasing day by day. Microplastic causes the destruction of soil structure; destroys soil microbiota, cause depletion of nutrients in the soil, and their absorption by plants decreases plant growth. Apart from other environmental problems caused by microplastic, human health is also badly affected by microplastic pollution present in the terrestrial environment. The presence of microplastics in the human body has been confirmed. Microplastic enters into the body of humans in different possible ways. According to their way of entering the body, microplastics cause different diseases in humans. MPs also cause negative effects on the human endocrine system. At the ecosystem level, the impacts of microplastic are interconnected and can disrupt ecological processes. Although recently different papers have been published on several aspects of the microplastic present in the terrestrial environment but there is no complete overview that focus on the interrelationship of MPs in plants, and soil and their effect on higher animals like a human. This review provides a completely detailed overview of existing knowledge about sources, occurrences, transport, and effects of microplastic on the food chain and soil quality and their ecotoxicological effects on plants and humans.


Assuntos
Microplásticos , Poluentes Químicos da Água , Animais , Humanos , Microplásticos/toxicidade , Plásticos/toxicidade , Ecossistema , Poluição Ambiental , Solo , Plantas , Monitoramento Ambiental , Poluentes Químicos da Água/análise
18.
ACS Omega ; 8(21): 18811-18822, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37273621

RESUMO

Semisynthetic modifications of natural products have bestowed us with many anticancer drugs. In the present work, a natural product, eugenol, has been modified synthetically to generate new anticancer agents. The final compounds were structurally confirmed by NMR, IR, and mass techniques. From the cytotoxicity results, compound 17 bearing morpholine was found to be the most active cytotoxic agent with IC50 1.71 (MCF-7), 1.84 (SKOV3), and 1.1 µM (PC-3) and a thymidylate synthase (TS) inhibitor with an IC50 of 0.81 µM. Further cellular studies showed that compound 17 could induce apoptosis and arrest the cell cycle at the S phase in PC-3 carcinoma. The docking study strongly favors compound 17 to be a TS inhibitor as it displayed a similar interaction to 5-fluorouracil. The in silico pharmacokinetics and DFT computational studies support the results obtained from docking and biological evaluation and displayed favorable pharmacokinetic profile for a drug to be orally available. Compound 17 was found to be a promising TS inhibitor which could suppress DNA synthesis and consequently DNA damage in prostate cancer cells.

19.
Int J Pharm ; 640: 123023, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37150270

RESUMO

A newly synthesized nanoplatform of hyaluronic acid and chitosan nanoparticles (HA/CNPs) was applied to improve the therapeutic efficacy and protection of bone marrow mesenchymal stem cells (BM-MSCs) against cisplatin (CDDP)-induced nephrotoxicity in rats. CDDP administration causes significant increases in levels of serum creatinine (SCr), urea, and KIM-1 coupled with significant albumin level falls, as indicative of acute renal dysfunction. Moreover, the level of the antioxidant enzyme (GSH) was significantly decreased, while the levels of lipid peroxidation (MDA) and inflammatory (IL-6) and apoptotic (caspase-3) markers were significantly increased, indicating a decline in the kidney's antioxidant defense and increased inflammation. In contrast, when rats were pre-treated with either MSCs or MSCs-HA/CNPs before receiving CDDP, the levels of SCr, urea, KIM-1, MDA, IL-6, and caspase-3 were significantly decreased with simultaneous significant rises in GSH and albumin, impelling a great improvement in the antioxidant and anti-inflammatory defenses of the kidney as well as its functions. Intriguingly, MSCs-HA/CNPs were more effective against caspase-3 than MSCs alone, revealing the high anti-apoptotic capability of HA/CNPs. This finding suggests that HA/CNPs could effectively protect MSCs from oxidative stress and apoptosis and thus increase their stability and longevity.


Assuntos
Quitosana , Células-Tronco Mesenquimais , Ratos , Animais , Cisplatino/toxicidade , Cisplatino/metabolismo , Ácido Hialurônico/farmacologia , Caspase 3/metabolismo , Quitosana/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Interleucina-6/metabolismo , Rim , Adjuvantes Imunológicos/farmacologia , Estresse Oxidativo , Ureia/metabolismo , Apoptose
20.
Int J Biol Macromol ; 242(Pt 4): 124985, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37230447

RESUMO

AIM: In the present investigation, we compared the effects of mesenchymal stem cells extracted from bone marrow (BMSCs) and crab chitosan nanoparticles (CCNPs) on renal fibrosis in cisplatin (CDDP)-induced kidney injury rats. MATERIAL AND METHODS: 90 male Sprague-Dawley (SD) rats were divided into two equal groups and alienated. Group I was set into three subgroups: the control subgroup, the CDDP-infected subgroup (acute kidney injury), and the CCNPs-treated subgroup. Group II was also divided into three subgroups: the control subgroup, the CDDP-infected subgroup (chronic kidney disease), and the BMSCs-treated subgroup. Through biochemical analysis and immunohistochemical research, the protective effects of CCNPs and BMSCs on renal function have been identified. RESULTS: CCNPs and BMSC treatment resulted in a substantial rise in GSH and albumin and a decrease in KIM-1, MDA, creatinine, urea, and caspase-3 when compared to the infected groups (p < 0.05). CONCLUSION: According to the current research, chitosan nanoparticles and BMSCs may be able to reduce renal fibrosis in acute and chronic kidney diseases caused by CDDP administration, with more improvement of kidney damage resembling normal cells after CCNPs administration.


Assuntos
Injúria Renal Aguda , Braquiúros , Quitosana , Células-Tronco Mesenquimais , Ratos , Masculino , Animais , Cisplatino/efeitos adversos , Quitosana/farmacologia , Ratos Sprague-Dawley , Rim , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Fibrose
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