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The purpose of this study was to enhance the topical delivery of 5-Fluorouracil (5-FU), a cancer treatment, by developing a nanoemulgel formulation. Glycyrrhizin (GLY), a natural penetration enhancer has been investigated to exhibit synergistic effects with 5-FU in inhibiting melanoma cell proliferation and inducing apoptosis, Hence, GLY, along with suitable lipids was utilized to create an optimized nanoemulsion (NE) based gel. Solubility studies and ternary phase diagram revealed isopropyl myristate (IPM), Span 80, Tween 80 as Smix and Transcutol P as co-surfactant. IPM demonstrates excellent solubilizing properties facilitates higher drug loading, ensuring efficient delivery to the target site.,The optimized formulation consisting of 40 % IPM, 30 % of mixture of Tween80: Span80 (Smix) and 15 % Transcutol P provides with a nanometric size of 64.1 ± 5.13 nm and drug loading of 97.3 ± 5.83 %. The optimized formulation observed with no creaming and breakeing of NE and found thermodynamically stable during different stress conditions (temperatures of 4.0 °C and 45.0 °C) and physical thawing (-21.0 ± 0.50 °C to 20.0 ± 0.50 °C). The NE was then transformed into a nanoemulgel (NEG) using 1.5 % w/w Carbopol base and 0.1 % w/w glycyrrhizin. The ex vivo permeability studies showed significant enhancements in drug permeability with the GLY-based 5-FU-NEG formulation compared to pure 5-FU gel in excised pig skin upto1440 min in PBS 7.4 as receptor media. The IC50 values for Plain 5-FU gel, 5-FU-NEG, and GLY-based 5-FU-NEG were found to be 20 µg/mL, 1.1 µg/mL, and 0.1 µg/mL, respectively in B16F10 cell lines. The percentage intracellular uptake of GLY-5-FU-NEG and 5-FU-NEG was found to be 44.3 % and 53.6 %, respectively. GLY-based 5-FU-NEG formulation showed alterations in cell cycle distribution, in compared to 5-FU-NE gel. The overall findings suggest that the GLY-based 5-FU-NEG holds promise for improving anti-melanoma activity.
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A twenty-four month long observational study conducted in an Asia's largest brackish water ecosystem, Chilika Lagoon, India, aimed to unravel dissolved organic matter (DOM) dynamics in this tropical brackish water ecosystem. The study assessed the interplay between allochthonous and autochthonous DOM sources during lean and active flow periods based on regional rainfall. Dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) fluxes were analyzed, considering catchment runoff, phytoplankton production, benthic-pelagic interactions, and sea-lagoon exchanges as contributors. Contrary to conventional thinking, the study found autochthonous processes to be more significant than conservative mixing in shaping DOM dynamics. It introduced a novel conceptual model illustrating the multifaceted origins of DOM, encompassing catchment runoff, phytoplankton, benthic-pelagic interactions, bacterial activity, and sea-lagoon exchanges. These findings underscore the importance of holistic management strategies for Chilika Lagoon to preserve its ecological health, given its vital role in global carbon cycling, fisheries, and aquaculture.
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Matéria Orgânica Dissolvida , Ecossistema , Fitoplâncton , Águas Salinas , ÁsiaRESUMO
The largest continental shelf Oxygen Minimum Zone (OMZ) in the world is formed along the Indian western shelf in the eastern Arabian Sea during the Southwest Monsoon [(SWM); June-September], which is a natural pollution event associated with the coastal upwelling. This study examines the composition, abundance, and distribution of copepods during the Northeast Monsoon [(NEM); November to February] and SWM in 50 m depth zones along the Indian western shelf in the eastern Arabian Sea. The NEM was characterised by warm, stratified, and low-salinity waters in the southeast Arabian Sea and cold, high-salinity, and well-mixed waters in the northeastern Arabian Sea. During the SWM, cold and Dissolved Oxygen (DO) deficient waters (<22 µM/0.5 ml L-1), which are the signs of coastal upwelling, were evident all along the study zone, but with more intensity off Kochi, Mangalore, and Goa in the south than off Mumbai and Okha in the north. The zooplankton total biomass and abundance showed seasonality with a general decrease during the SWM (av. 3.68 ± 1.29 ml m-3 and av. 5711 ± 3096 Ind. m-3, respectively) compared to the NEM (av. 7.37 ± 2.17 ml m-3 and av. 14,473 ± 4966 Ind. m-3, respectively). At the same time, the abundance of Polychaeta and Siphonophora showed an increase during the SWM (av. 1187 ± 1055 Ind. m-3 and av. 169 ± 119 Ind. m-3, respectively), probably a result of the DO deficient waters associated with upwelling. Two striking seasonal features in Copepoda community were evident in this study: (a) a compositional shift from Cyclopoida dominant during the NEM to Calanoida dominant during the SWM, and (b) the coastal OMZ along the Indian western shelf during the SWM was dominated by Calanoida, which include oceanic OMZ species such as Pleuromamma indica, Lucicutia flavicornis, L.paraclausii, Eucalanus elongatus, Subeucalanus pileatus, S.subcrassus, and Clausocalanus furcatus. This forms a clear imprint for the extension of the oceanic OMZ into nearshore waters during the SWM due to coastal upwelling.
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Copépodes , Animais , Oxigênio , Oceanos e Mares , Biomassa , Índia , Estações do Ano , Água do MarRESUMO
This review has been undertaken to understand the effectiveness of ocean acidification on oceanic micronutrient metal cycles (iron, copper and zinc) and its potential impacts on marine biota. Ocean acidification will slow down the oxidation of Fe(II) thereby retarding Fe(III) formation and subsequent hydrolysis/precipitation leading to an increase in iron bioavailability. Further, the increased primary production sustains enzymatic bacteria assisted Fe(III) reduction and subsequently the binding of weaker ligands favours the dissociation of free Fe(II) ions, thus increasing the bioavailability. The increasing pCO2 condition increases the bioavailability of copper ions by decreasing the availability of free CO32- ligand concentration. The strong complexation by dissolved organic matter may decrease the bioavailable iron and zinc ion concentration. Since ocean acidification affects the bioavailability of essential metals, studies on the uptake rates of these elements by phytoplankton should be carried out to reveal the future scenario and its effect on natural environment.
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Ferro , Oligoelementos , Ferro/metabolismo , Cobre , Zinco , Água do Mar , Micronutrientes , Concentração de Íons de Hidrogênio , Acidificação dos Oceanos , Metais , Ácidos , Compostos Férricos , Íons , Compostos FerrososRESUMO
Cancer stands as one of the deadliest diseases, ranking second in terms of its global impact. Despite the presence of numerous compelling theories concerning its origins, none have succeeded in fully elucidating the intricate nature of this ailment. Among the prevailing concerns in today's world, breast cancer proliferation remains a significant issue, particularly affecting females. The abnormal proliferation of the PI3K pathway emerges as a prominent driver of breast cancer, underscoring its role in cellular survival and proliferation. Consequently, targeting this pathway has emerged as a leading strategy in breast cancer therapeutics. Within this context, the present article explores the current landscape of anti-tumour drug development, focusing on structural activity relationships (SAR) in PI3K targeting breast cancer treatment. Notably, certain moieties like triazines, pyrimidine, quinazoline, quinoline, and pyridoxine have been explored as potential PI3K inhibitors for combating breast cancer. Various heterocyclic small molecules are undergoing clinical trials, such as Alpelisib, the first orally available FDA-approved drug targeting PI3K; others include buparlisib, pictilisib, and taselisib, which inhibit class I PI3K. These drugs are used for the treatment of breast cancer but still have various side effects with their high cost. Therefore, the primary goal of this review is to include all current advances in the development of anticancer medicines that target PI3K over-activation in the treatment of breast cancer.
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Antineoplásicos , Neoplasias da Mama , Inibidores de Fosfoinositídeo-3 Quinase , Feminino , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase/farmacologiaRESUMO
Neuroblastoma, the most common childhood solid tumor, originates from primitive sympathetic nervous system cells. Epoxyazadiradione (EAD) is a limonoid derived from Azadirachta indica, belonging to the family Meliaceae. In this study, we isolated the EAD from Azadirachta indica seed and studied the anti-cancer potential against neuroblastoma. Herein, EAD demonstrated significant efficacy against neuroblastoma by suppressing cell proliferation, enhancing the rate of apoptosis and cycle arrest at the SubG0 and G2/M phases. EAD enhanced the pro-apoptotic Caspase 3 and Caspase 9 and inhibited the NF-kß translocation in a dose-dependent manner. In order to identify the specific EAD target, a gel-free quantitative proteomics study on SH-SY5Y cells using Liquid Chromatography with tandem mass spectrometry was done in a dose-dependent manner, followed by detailed bioinformatics analysis to identify effects on protein. Proteomics data identified that Enolase1 and HSP90 were up-regulated in neuroblastoma. EAD inhibited the expression of Enolase1 and HSP90, validated by mRNA expression, immunoblotting, Enolase1 and HSP90 kit and flow-cytometry based bioassay. Molecular docking study, Molecular dynamic simulation, and along with molecular mechanics/Poisson-Boltzmann surface area analysis also suggested that EAD binds at the active site of the proteins and were stable throughout the 100 ns Molecular dynamic simulation study. Overall, this study suggested EAD exhibited anti-cancer activity against neuroblastoma by targeting Enolase1 and HSP90 pathways.Communicated by Ramaswamy H. Sarma.
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The development of an efficient and innovative drug delivery system is essential to improve the pharmacological parameters of the medicinal compound or drug. The technique or manner used to improve the pharmacological parameters plays a crucial role in the delivery system. In the current scenario, various drug delivery systems are available where nanotechnology has firmly established itself in the field of drug delivery. One of the most prevalent elements is carbon with its allotropic modifications such as graphene-based nanomaterials, carbon nanotubes, carbon dots, and carbon fullerenes, these nanomaterials offer notable physiochemical and biochemical properties for the delivery applications due to their smaller size, surface area, and ability to interact with the cells or tissues. The exceptional physicochemical properties of carbon-based 2D nanomaterials, such as graphene and carbon nanotubes, make them attractive candidates for drug delivery systems. These nanomaterials offer a large surface area, high drug loading capacity, and tunable surface chemistry, enabling efficient encapsulation, controlled release, and targeted delivery of therapeutic agents. These properties of the nanomaterials can be exploited for drug delivery applications, like assisting the target delivery of drugs and aiding combination molecular imaging. This review emphasizes the drug delivery system and the role of carbon-based nanomaterials in drug delivery systems. Carbon-based 2D nanomaterials present a wealth of opportunities for advanced drug delivery systems. Their exceptional properties and versatility offers great potential in improving therapeutic efficacy, minimizing side effects, and enabling personalized medicine.
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Cladribine is a purine nucleoside found to enhance toxic amyloid protein and cause memory impairment. Patients following chemotherapy treatment commonly suffer from cognitive deficits more prevalent in the elderly than adults. A previous research study revealed that cladribine has a high affinity to the brain, increases the level of amyloid precursor protein, and results in learning deficits. The study was designed to validate an animal model of cladribine administration to rats through mitochondrial oxidative stress, inflammation, apoptosis, tau phosphorylation, and amyloid-ß (1-42) accumulation. In this study, all rats were orally given cladribine (0.5 and 1 mg/kg) for 28 days, resulting in impaired spatial memory confirmed by behavioural activity. On day 29, all rats were euthanized, and the hippocampal tissues were isolated and used for the estimation of neuroinflammatory markers, biochemicals parameters (glutathione, catalase, lipid peroxidation, and nitrite), amyloid-ß (1-42) level, neurotransmitters, and nuclear factor kappa B analysis. Cladribine administration significantly elevated cytokines release, dysbalanced neurotransmitter concentration, and promoted the Aß accumulation and hyperphosphorylation of tau protein. Our study outcome confirmed that cladribine produces cognitive impairment via activation of Nuclear factor kappa B, mitochondrial oxidative stress and dysbalanced of the endogenous antioxidant defence system.
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Doença de Alzheimer , Proteínas tau , Humanos , Ratos , Animais , Idoso , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Cladribina/farmacologia , Cladribina/metabolismo , Cladribina/uso terapêutico , Fosforilação , NF-kappa B/metabolismo , Doenças Neuroinflamatórias , Hipocampo/metabolismo , Peptídeos beta-Amiloides/metabolismo , Apoptose , Estresse Oxidativo , Modelos Animais de DoençasRESUMO
The study assessed the Cochin estuary and adjacent coastal Arabian Sea for their seasonal variation in nitrate (NO3-) and ammonium (NH4+) uptake rates by total and nano + picoplankton using the 15N tracer technique. The results suggested that the NO3- and NH4+ uptake rates in the Cochin estuary are higher than those in the adjacent coastal Arabian Sea. NO3- and NH4+ uptake rates in the nearshore stations in the off Cochin station were high, indicating the influence of the eutrophic estuary. NO3- and NH4+ uptake rates conducted in off Mangalore transect were significantly lower than those of the off Cochin as it does not have an exchange with eutrophic systems. The nano + picoplankton's contribution to the total DIN uptake rates in the Cochin estuary was 77-98 %, indicating the relevance of nano + pico phytoplankton in the N cycling of the region.
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Estuários , Nitrogênio , Estações do Ano , Nitrogênio/análise , Fitoplâncton , Nitratos/análiseRESUMO
α -Glucosidase is an enzyme present near the brush boundary of the small intestine that is essential in the hydrolysis of carbohydrates to glucose. Because inhibiting this enzyme slows the release of glucose, α-Glucosidase inhibitors are appealing medications for treating diabetes as a carbohydrate-related illness. The present study includes the design, synthesis and antidiabetic potential of novel triazole based indole derivatives as α-glucosidase inhibitor. Among them, the compound R1 was found to be most potent with promising candidate with IC50 value of 10.1 µM and R2 and R3 showed the good inhibitory potency with IC50 values 12.95 µM, 11.35 µM, respectively when compared to the standard drug acarbose having IC50 value of 13.5 µM. In in vivo studies, body weight of the mice was increased when compared to standard drug acarbose, the blood glucose level of the mice was decreased, same as the total cholesterol level, LDL, and triglycerides level decreased in comparison to standard drug. The level HDL was increased as it is a good cholesterol in comparison to standard drug acarbose. Furthermore, these synthesized compounds were docked with α-glucosidase using PDB ID:3WY1 which showed that compound R1 having good docking score -6.734 kcal/mol and compound R2, R3 showed docking score -6.14, -6.10 kcal/mol, respectively when compared with standard acarbose having docking score -4.55 kcal/mol. R1 showed the similar interaction with amino acid PHE166, GLU271, comparison with standard drug Acarbose. The synthesized compounds have been confirmed for antidiabetic activity and may be used for further development of potent compounds.
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Inibidores de Glicosídeo Hidrolases , Cardiopatias , Camundongos , Animais , Inibidores de Glicosídeo Hidrolases/química , Hipoglicemiantes/química , Acarbose , Triazóis/química , Simulação de Acoplamento Molecular , Glucose , alfa-Glucosidases/metabolismo , Indóis , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
The growing nanoparticulate pollution (e.g. engineered nanoparticles (NPs) or nanoplastics) has been shown to pose potential threats to human health. In particular, sensitive populations such as pregnant women and their unborn children need to be protected from harmful environmental exposures. However, developmental toxicity from prenatal exposure to pollution particles is not yet well studied despite evidence of particle accumulation in human placenta. Our study aimed to investigate how copper oxide NPs (CuO NPs; 10-20 nm) and polystyrene nanoplastics (PS NPs; 70 nm) impact on gene expression in ex vivo perfused human placental tissue. Whole genome microarray analysis revealed changes in global gene expression profile after 6 h of perfusion with sub-cytotoxic concentrations of CuO (10 µg/mL) and PS NPs (25 µg/mL). Pathway and gene ontology enrichment analysis of the differentially expressed genes suggested that CuO and PS NPs trigger distinct cellular response in placental tissue. While CuO NPs induced pathways related to angiogenesis, protein misfolding and heat shock responses, PS NPs affected the expression of genes related to inflammation and iron homeostasis. The observed effects on protein misfolding, cytokine signaling, and hormones were corroborated by western blot (accumulation of polyubiquitinated proteins) or qPCR analysis. Overall, the results of the present study revealed extensive and material-specific interference of CuO and PS NPs with placental gene expression from a single short-term exposure which deserves increasing attention. In addition, the placenta, which is often neglected in developmental toxicity studies, should be a key focus in the future safety assessment of NPs in pregnancy.
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Cobre , Nanopartículas , Gravidez , Humanos , Feminino , Cobre/toxicidade , Poliestirenos/toxicidade , Microplásticos , Transcriptoma , Placenta , Nanopartículas/toxicidade , ÓxidosRESUMO
Approximately 2% to 3% of men and 6% to 7% of women suffer from severe depressive disorders. The existing drugs only partially relieve symptoms for roughly 40% of these patients. The majority of antidepressant drugs are based on theories that are now 50 to 60 years old, and the sector is in critical need of new drug development targets. In the recent decade, numerous genes have been connected to depression in animal models, and serious depression does run in families in humans, indicating both a genetic and environmental component. Depression has been linked to the malfunctioning of serotonin signaling genes, including p11, SERT, etc, according to earlier research. Gene therapy for depression has been found in some instances to be relatively safe, despite the fact that it may seem riskier and more invasive than medication. Hence, there is a growing field regarding the safest delivery mechanisms of these genes that treat major depressive disorders permanently. Hence, the present review summarized the delivery mechanisms of various genes responsible for depressive disorders along with their molecular mechanisms and delivery at the cellular level.
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Transtorno Depressivo Maior , Masculino , Animais , Humanos , Feminino , Pessoa de Meia-Idade , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/tratamento farmacológico , Antidepressivos/uso terapêutico , Terapia GenéticaRESUMO
Phytoplankton size classes (PSCs) are important in marine ecosystems because they organise the food chain and trophic pathways, which determine the overall biological environment. Based on three FORV Sagar Sampada cruises, the current study provides changes in PSCs in the Northeastern Arabian Sea (NEAS; north of 18 N) during different phases of the Northeast Monsoon [NEM (November-February)]. During all three phases of NEM such as early (November), peak (December), and late (February), in-situ chlorophyll-a fractionation data revealed that nanoplankton (2-20 µm) predominated, followed by microplankton (>20 µm) and picoplankton (0.2-2.0 µm). This was primarily because winter convective mixing in the NEAS maintains only a moderate level of nutrients in the surface mixed layer, which is more conducive to the dominance of nanoplankton. Brewin et al. (2012) and Sahay et al. (2017) have satellite-based PSC estimation algorithms; the former was developed for the entire Indian Ocean, while the latter is a modification of the former for the Noctiluca bloom-infested NEAS, with a claim that such blooms are typical of the NEM. When current in-situ PSCs data were compared to algorithm-based NEM data, Brewin et al. (2012) revealed a more realistic PSCs contribution pattern, especially in oceanic waters, with nanoplankton predominating except during early NEM. But the PSCs data from Sahay et al. (2017) showed a high degree of variation from the in-situ data, demonstrating the dominance of pico- and microplankton and a notably small contribution from the nano phytoplankton. The current study showed that Sahay et al. (2017) is inferior to Brewin et al. (2012) at quantifying PSCs in the NEAS without Noctiluca blooms, and provided evidence to show that Noctiluca blooms are not a typical feature of the region during the NEM.
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Dinoflagellida , Fitoplâncton , Tecnologia de Sensoriamento Remoto , Ecossistema , Monitoramento Ambiental/métodos , Oceano Índico , Estações do AnoRESUMO
Poorly soluble drug molecules/phytoconstituents are still a growing concern for biopharmaceutical delivery in the body. Polymeric micelles are the amphiphilic block copolymers and have been widely investigated as targeted nanocarriers for the treatment of various ailments. The versatility of nanocarriers is the self-assembling properties in the aqueous medium and forms a stable isotropic system in vivo. The hydrophobic core-hydrophilic shell configuration of the polymers used to the mixed micelles makes easy encapsulation of hydrophobic and hydrophilic drugs into the core. Polymeric micelles can also be combined with targeting ligands that increase their uptake by specific cells, decreasing off-target effects, and provide enhanced therapeutic effect. In the present review, we primarily focused on a critical appraisal of Polymeric micelles along with the method of preparation, mechanism of micelle formulation, and the ongoing formulations under clinical trials. In addition, the biological applications of this isotropic nanocarrier have been duly presented in each route of administration along with suitable case studies.
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Micelas , Polímeros , Polímeros/química , Interações Hidrofóbicas e Hidrofílicas , LigantesRESUMO
HSP90, one important class of chaperons has been intensively investigated as a promising and novel class of drug target for cancer therapy from the past few decades. A series of 2-((4-resorcinolyl)-5-aryl-1, 2, 3-triazol-1-yl) acetate derivatives were taken in the present study for the generation of pharmacophore based models, predictive 3 D-QSAR models, docking and ZINC screening studies against HSP90. The investigation included 30 ligands which emerged DHRRR_1 having survival score of 5.59 was found the most effective pharmacophore model. The generated third PLS factor includes a model with significant Q2, R2, and R2 CV values as 0.62, 0.77, and 0.50, respectively. The molecular docking studies against HSP90 showed interactions with important amino acids such as GLY-97, ASN-106, THR-184, ASN-51, PHE-138 and SER-52 required for HSP90 inhibitory activity. According to the docking analysis compound 34 was the top scoring compound, had a docking score of -10.98 from the series and showed interactions with amino acids likeASP-93, GLY-97, AND ASP-102. Using pharmacophore characteristics, the virtual screening investigation was carried out and DHRRR_1 showed the potential ZINC compounds. The ZINC compounds ZINC72417069 and ZINC77522480 showed best XP docking scores (-8.205 and -7.103 consecutively) and the top-scoring compound ZINC72417069 displayed amino acid binding affinity with GLY-97, ASN-106, and THR-184 against HSP90, PDB ID: 2xjx. These ZINC compounds can be used as target for HSP90. The result of the study may further help to the scientist for the design and development of potential HSP90 inhibitors.
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Antineoplásicos , Neoplasias , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Proteínas de Choque Térmico HSP90 , Aminoácidos , Triazóis/farmacologiaRESUMO
Cancer is becoming a global threat as its treatment accounts for many challenges. Hence, newer inventions prioritize the requirement of developing novel anticancer agents. In this context, kinases have been exclusively investigated and developed as a promising and novel class of drug targets for anticancer regimen. Indole derivatives have been found to be most effective for targeting multiple kinases, such as PIM, CDK, TK, AKT, SRC, PI3K, PKD, GSK, etc., to inhibit cell proliferation for cancer. Recently, a group of researchers have proposed their research outcomes related to this moiety, such as Zhang et al. described some potent PI3K inhibitors by substitution at the 4th position of the indole ring. Kassis et al. enumerated several potent CDK5 inhibitors by substituting the 2nd and 6th positions of the indole ring. In the present review, we have taken the initiative to summarize structure-activity relationship (SAR) studies of indole derivatives as kinase inhibitors for the development of potential inhibitors.
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Antineoplásicos , Neoplasias , Humanos , Fosfatidilinositol 3-Quinases , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Relação Estrutura-Atividade , Proliferação de Células , Indóis/farmacologia , Indóis/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Estrutura MolecularRESUMO
HMG-CoA reductase inhibitors (statins), lipoprotein lipase activators (PPARα agonists) or fibrates are commonly used for controlling increased lipid levels in hyperlipidemia. Fenofibrate (FEN) belongs to the second generation prodrug fibric acid (isobutyric acid) derivative belonging to lipoprotein lipase activator class of drug. Results of clinical studies suggest that FEN can substantially reduce severe acute respiratory syndrome coronavirus 2. alpha and beta variant infection in human cell efficiently. This review article provides an in-depth examination of critical analytical methodologies used in the pharmaceutical analysis of FEN in pure forms, biological samples and pharmaceuticals. According to literature study reports several analytical techniques have been used for determination of FEN alone or in the combined dosage forms. Based on the literature, it was determined that high-performance liquid chromatography and UV/vis-spectrophotometry are the most widely used methods for FEN analysis. Sahoo et al. have developed the best HPLC method in bulk and pharmaceutical dosage form with the retention time of 19.268 min using phosphate buffer (pH 3.0): acetonitrile in the ratio of 30:70 (% v/v) as mobile phase. The information presented here may provide a solid foundation for future research on FEN in the field of drug analysis.
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COVID-19 , Fenofibrato , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Fenofibrato/análise , Hipolipemiantes , SARS-CoV-2 , Cromatografia Líquida de Alta Pressão/métodos , Preparações FarmacêuticasRESUMO
Glycosylated nanoparticles (NPs) have drawn a lot of attention in the biomedical field over the past few decades, particularly in applications like targeted drug delivery. Mannosylated NPs and mannan-binding lectins/proteins (MBL/MBP) are emerging as promising tools for delivery of drugs, medicines, and enzymes to targeted tissues and cells as nanocarriers, enhancing their therapeutic benefits while avoiding the adverse effects of the drug. The occurrence of plenty of lectin receptors and their mannan ligands on cell surfaces makes them multifaceted carriers appropriate for specific delivery of bioactive drug materials to their targeted sites. Thus, the present review describes the tethering of mannose (Man) to several nanostructures, like micelles, liposomes, and other NPs, applicable for drug delivery systems. Bioadhesion through MBL-like receptors on cells has involvements applicable to additional arenas of science, for example gene delivery, tissue engineering, biomaterials, and nanotechnology. This review also focuses on the role of various aspects of drug/antigen delivery using (i) mannosylated NPs, (ii) mannosylated lectins, (iii) amphiphilic glycopolymer NPs, and (iv) natural mannan-containing polysaccharides, with most significant applications of MBL-based NPs as multivalent scaffolds, using different strategies. Graphical abstract: Mannosylated NPs and/or MBL/MBP are coming up as viable and versatile tools as nanocarriers to deliver drugs and enzymes precisely to their target tissues or cells. The presence of abundant number of lectin receptors and their mannan ligands on cell surfaces makes them versatile carriers suitable for the targeted delivery of bioactive drugs.
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Pulmonary arterial hypertension (PAH) is an uncommon condition marked by elevated pulmonary artery pressure that leads to right ventricular failure. The majority of drugs are now been approved by FDA for PAH, however, several biopharmaceutical hindrances lead to failure of the therapy. Various novel drug delivery systems are available in the literature from which lipid-based nanoparticles i.e. solid lipid nanoparticle is widely investigated for improving the solubility and bioavailability of drugs. In this paper, the prototype phytoconstituents used in pulmonary arterial hypertension have limited solubility and bioavailability. We highlighted the novel concepts of SLN for lipophilic phytoconstituents with their potential applications. This paper also reviews the present state of the art regarding production techniques for SLN like High-Pressure Homogenization, Micro-emulsion Technique, and Phase Inversion Temperature Method, etc. Furthermore, toxicity aspects and in vivo fate of SLN are also highlighted in this review. In a nutshell, safer delivery of phytoconstituents by SLN added a novel feather to the cap of successful drug delivery technologies.
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OBJECTIVE: Three-dimensional computed tomography reconstruction of the face has recently been presented as a newer diagnostic tool in coronavirus disease 2019 associated mucormycosis. This study was conducted to compare three-dimensional computed tomography reconstruction with conventional two-dimensional computed tomography in coronavirus disease 2019 associated mucormycosis. METHODS: A total of 123 mucormycosis patients underwent three-dimensional computed tomography reconstruction after a comprehensive clinical investigation. The involvement of the facial skeleton was noted. RESULTS: The anterior maxillary wall was most commonly involved (9.8 per cent). Involvement of the lateral maxillary wall was noted in 6.5 per cent of patients. Sixty-seven patients (54.5 per cent) underwent endoscopic surgery, 22 (17.9 per cent) underwent open surgical procedures, and 12 (9.8 per cent) had combined endoscopic and open surgical procedures. In 21 patients (17.1 per cent), open surgery was performed in the first instance based on additional three-dimensional computed tomography findings, and revision surgical procedures were avoided. CONCLUSION: Three-dimensional computed tomography of the face was found to be superior in determining the extent of disease. It reduces delays in diagnosis, facilitates surgical planning and minimises the need for multiple surgical procedures.