RESUMEN

Despite significant advancements in chemotherapy, effective treatments for advanced cancer stages remain largely elusive due to chemoresistance. Resistance to anticancer agents in cancer cells can arise through various mechanisms, including multi-drug resistance, inhibition of apoptosis, modification of drug targets, and enhancement of DNA repair capabilities. Consequently, there is a critical need for agents that can suppress the molecular signatures responsible for drug resistance. Piperine, an active alkaloid extracted from Piper nigrum L. (black pepper), is one such agent that has been extensively studied for its potential in addressing chronic diseases, including cancer. Piperine's antineoplastic properties are mediated through the regulation of numerous key cellular signaling pathways and the modulation of various biological processes. Its capability to enhance drug bioavailability and counteract mechanisms of drug resistance, such as the inhibition of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP-1), emphasizes its potential as an adjunct in cancer therapy. Research across various cancer types has demonstrated piperine's role in chemosensitization by targeting P-gp and MRP-1 and altering drug-metabolizing enzymes. This review provides a comprehensive analysis of piperine's pharmacological characteristics and its capacity to modulate several cellular signaling pathways involved in drug resistance. Furthermore, the review emphasizes how piperine, when used in conjunction with other chemotherapeutic agents or natural compounds, can enhance therapeutic effects, leading to improved outcomes in cancer treatment.

Asunto(s)

Alcaloides , Benzodioxoles , Resistencia a Antineoplásicos , Neoplasias , Piperidinas , Alcamidas Poliinsaturadas , Alcamidas Poliinsaturadas/farmacología , Benzodioxoles/farmacología , Benzodioxoles/uso terapéutico , Humanos , Piperidinas/farmacología , Piperidinas/uso terapéutico , Alcaloides/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Animales , Sinergismo Farmacológico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Piper nigrum/química

RESUMEN

The present study aimed to fabricate innovative fibrous materials with various biological activities from poly(3-hydroxybutyrate), sodium hyaluronate (HA), chitosan (Ch), Melissa officinalis (MO), Hypericum perforatum (HP) extract, or a combination of both extracts. Electrospinning or electrospinning followed by dip coating and the subsequent formation of a polyelectrolyte complex were the methods used to prepare these materials. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) were applied for investigating the morphology of materials, their thermal characteristics, and their surface chemical composition. The composition and design of the mats had an influence on the in vitro release behavior of the main bioactive compounds present in the MO and HP extracts incorporated in the materials. It was found that as-created materials comprising a combination of both extracts and a Ch/HA complex exerted higher antioxidant activity than that of (non-)coated MO-containing mats and Ch/HA-coated mats containing HP. The novel materials manifested antibacterial efficacy towards the pathogenic bacteria S. aureus and E. coli, as evidenced by the performed microbiological screening. Furthermore, the mats possessed a great growth inhibitory effect on HeLa cancer cells but had a less pronounced effect on the growth of normal mouse BALB/3T3 fibroblasts. The loading of both extracts in the mats and the formation of coating led to the enhancement of the in vitro anticancer and antibacterial activities of the materials. Thus, the novel materials have potential for use in local cancer therapy as well as for use as wound dressings.

RESUMEN

Ophiocordyceps xuefengensis (O. xuefengensis), the sister taxon of Ophiocordyceps sinensis (O. sinensis), is consumed as a "tonic food" due to its health benefits. However, little is known regarding the chemistry and bioactivity of O. xuefengensis. In this study, we characterized 80 indole-based alkaloids in the ethyl acetate fraction of O. xuefengensis by high performance liquid chromatography-quadrupole time of flight mass spectrometry (HPLC-Q-TOF-MS/MS), of which 54 indole-based alkaloids were identified as possibly new compounds. Furthermore, 29 of these compounds were established as potential anti-cancer compounds by ligand fishing combined with HPLC-Q-TOF-MS/MS. Moreover, molecular docking identified the NH- and OH- groups of these compounds as the key active groups. The present study has expanded the knowledge on the characteristic indole-based alkaloids and anti-cancer activity of O. xuefengensis.

Asunto(s)

Antineoplásicos , Simulación del Acoplamiento Molecular , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Humanos , Cromatografía Líquida de Alta Presión/métodos , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Alcaloides/farmacología , Alcaloides/química , Alcaloides Indólicos/farmacología , Alcaloides Indólicos/química , Indoles/química , Indoles/farmacología

RESUMEN

Quercetin is a natural flavonoid with various pharmacological actions such as anti-inflammatory, antioxidant, antimicrobial, anticancer, antiviral, antidiabetic, cardioprotective, neuroprotective, and antiviral activities. Looking at these enormous potentials, researchers have explored how they can be used to manage numerous cancers. It's been studied for cancer management due to its anti-angiogenesis, anti-metastatic, and antiproliferative mechanisms. Despite having these proven pharmacological activities, the clinical use of quercetin is limited due to its first-- pass metabolism, poor solubility, and bioavailability. To address these shortcomings, researchers have fabricated various nanocarriers-based formulations to fight cancer. The present review overshadows the pharmacological potential, mechanisms, and application of nanoformulations against different cancers.

RESUMEN

Naphthylisoquinoline alkaloids are a fascinating class of natural biaryl compounds. They show characteristic mono- and dimeric scaffolds, with chiral axes and stereogenic centers. Since the appearance of the last comprehensive overview on these secondary plant metabolites in this series in 1995, the number of discovered representatives has tremendously increased to more than 280 examples known today. Many novel-type compounds have meanwhile been discovered, among them naphthylisoquinoline-related follow-up products like e.g., the first seco-type (i.e., ring-opened) and ring-contracted analogues. As highlighted in this review, the knowledge on the broad structural chemodiversity of naphthylisoquinoline alkaloids has been decisively driven forward by extensive phytochemical studies on the metabolite pattern of Ancistrocladus abbreviatus from Coastal West Africa, which is a particularly "creative" plant. These investigations furnished a considerable number of more than 80-mostly new-natural products from this single species, with promising antiplasmodial activities and with pronounced cytotoxic effects against human leukemia, pancreatic, cervical, and breast cancer cells. Another unique feature of naphthylisoquinoline alkaloids is their unprecedented biosynthetic origin from polyketidic precursors and not, as usual for isoquinoline alkaloids, from aromatic amino acids-a striking example of biosynthetic convergence in nature. Furthermore, remarkable botanical results are presented on the natural producers of naphthylisoquinoline alkaloids, the paleotropical Dioncophyllaceae and Ancistrocladaceae lianas, including first investigations on the chemoecological role of these plant metabolites and their storage and accumulation in particular plant organs.

Asunto(s)

Alcaloides , Isoquinolinas , Humanos , Alcaloides/química , Alcaloides/farmacología , Alcaloides/metabolismo , Isoquinolinas/química , Isoquinolinas/farmacología , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Animales , Estructura Molecular

RESUMEN

A variety of active chemicals found in medicinal plants can be used to develop new medications with few adverse effects. In vitro and in silico analyses were used to evaluate the anticancer properties of Juniperus procera fruit and leaf extracts. Here, we show that the methanolic extract from J procera fruit and leaf extracts inhibits 2 human ovarian cancer cell lines, A2780CP and SKOV-3. The leaf extract demonstrated strong cytotoxicity against A2780CP with an IC50 of 1.2 µg/mL, almost matching the IC50 of the anticancer medication doxorubicin (0.9 µg/mL). Higher antioxidant activity was observed in the fruit than leaf extract. The molecular docking results showed that the active component, podocarpusflavone A, was the best-docked chemical with the human topoisomerase II alpha enzyme. According to our knowledge, this is the first in vitro study to show the cytotoxicity of J procera extracts against the 2 previously described human ovarian cancer cell lines. The fact that the podocarpusflavone A molecule may have an inhibitory effect on the human topoisomerase II alpha enzyme was also revealed by this first in silico analysis. Our findings imply that the J procera fruit and leaf methanolic extract has anticancer characteristics that may guide future in vivo studies.

RESUMEN

The Verongida order comprises several sponge families, such as Aplysinellidae, Aplysinidae, Ianthellidae, and Pseudoceratinidae, reported for producing bromotyrosine-derived compounds. First identified in 1913, bromotyrosine derivatives have since captivated interest notably for their antitumor and antimicrobial properties. To date, over 360 bromotyrosine derivatives have been reported. Our review focuses specifically on bromotyrosine derivatives newly reported from 2004 to 2023, by summarizing current knowledge about their chemical diversity and their biological activities.

Asunto(s)

Vendajes , Poríferos , Tirosina/análogos & derivados , Humanos , Animales

RESUMEN

This contribution insight on the cytotoxic and anticancer activities and molecular mechanism of phyto-reduced silver nanoparticles (AgNPs) in MCF-7 breast cancer cell lines. A simple, entirely green synthesis process was optimized for the phyto-reduction of AgNP (~12.7 nm) using aqueous leaf extracts of Indigofera heterantha. The structural and vibrational properties of biosynthesized AgNPs were extensively characterized using UV-Vis spectrophotometer, x-ray diffraction (XRD), dynamic light scattering (DLS), and Fourier transform Infrared spectroscopy (FTIR), while their shape and morphology was studied through scanning electron microscopy (SEM). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay indicates concentration dependent inhibition with IC50, 27.93 ± 2.10 µg/mL against MCF-7 cells and 294.38 ± 3.87 µg/mL against L929 cells. The manifested anticancer mechanism in MCF-7 cells was extensively studied using Acridine orange/ethidium bromide (AO/EB), 4',6-diamidino-2-phenylindole (DAPI) and Annexin-V/propedium iodide fluorescence microscopic assays. The level of reactive oxygen species (ROS) was measured using DCFH-DA fluorescent spectroscopy. Overall, the results show that AgNPs exhibit cytotoxic and apoptotic effect on breast cancer MCF-7 cells by damaging membrane integrity and nuclear fragmentation due to oxidative stress generated by elevated level of ROS. RESEARCH HIGHLIGHTS: Biomimetic synthesis of nano dimension size silver nanoparticles (AgNPs). Characterization of AgNPs through UV-Vis, DLS, XRD, FTIR, and SEM. Cytotoxic and anticancer effects of the biosynthesized AgNPs in L929 fibroblast cells and MCF7 breast cancer respectively. Determination of morphological, and nuclear changes triggered by AgNPs in MCF 7 breast cancer cells using fluorescent microscopy and flow cytometry. Apoptosis induction by AgNPs in cancer cells through oxidative stress generated by reactive oxygen species (ROS).

Asunto(s)

Antineoplásicos , Apoptosis , Neoplasias de la Mama , Supervivencia Celular , Nanopartículas del Metal , Extractos Vegetales , Especies Reactivas de Oxígeno , Plata , Humanos , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Células MCF-7 , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antineoplásicos/farmacología , Antineoplásicos/química , Especies Reactivas de Oxígeno/metabolismo , Supervivencia Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Hojas de la Planta/química , Tecnología Química Verde , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X

RESUMEN

2,5-Diketopiperazine (2,5-DKP) derivatives represent a family of secondary metabolites widely produced by bacteria, fungi, plants, animals, and marine organisms. Many natural products with DKP scaffolds exhibited various pharmacological activities such as antiviral, antifungal, antibacterial, and antitumor. 2,5-DKPs are recognized as privileged structures in medicinal chemistry, and compounds that incorporate the 2,5-DKP scaffold have been extensively investigated for their anticancer properties. This review is a thorough update on the anti-cancer activity of natural and synthesized 2,5-DKPs from 1997 to 2022. We have explored various aspects of 2,5-DKPs modifications and summarized their structure-activity relationships (SARs) to gain insight into their anticancer activities. We have also highlighted the novel approaches to enhance the specificity and pharmacokinetics of 2,5-DKP-based anticancer agents.

Asunto(s)

Antineoplásicos , Dicetopiperazinas , Antineoplásicos/farmacología , Antineoplásicos/química , Dicetopiperazinas/química , Dicetopiperazinas/farmacología , Humanos , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Relación Estructura-Actividad , Estructura Molecular , Productos Biológicos/química , Productos Biológicos/farmacología , Proliferación Celular/efectos de los fármacos

RESUMEN

Following nearly two decades of development, significant advancements have been achieved in PROTAC technology. As of the end of 2022, more than 20 drugs have entered clinical trials, with ARV-471 targeting estrogen receptor (ER) showing remarkable progress by entering phase III clinical studies. In 2022, significant progress has been made on multiple targets. The first reversible covalent degrader designed to target the KRASG12C mutant protein, based on cyclopropionamide, has been reported. Additionally, the activity HDCA1 degrader surpassed submicromolar levels during the same year. A novel FEM1B covalent ligand called EN106 was also discovered, expanding the range of available ligands. Furthermore, the first PROTAC drug targeting SOS1 was reported. Additionally, the first-in-class degraders that specifically target BRD4 isoforms (BRD4 L and BRD4 S) have recently been reported, providing a valuable tool for further investigating the biological functions of these isoforms. Lastly, a breakthrough was also achieved with the first degrader targeting both CDK9 and Cyclin T1. In this review, we aimed to update the PROTAC degraders as potential anticancer agents covering articles published in 2022. The design strategies, degradation effects, and anticancer activities were highlighted, which might provide an updated sight to develop novel PROTAC degraders with great potential as anticancer agents as well as favorable drug-like properties.

Asunto(s)

Antineoplásicos , Proteínas Nucleares , Factores de Transcripción , Antineoplásicos/farmacología , Antagonistas de Estrógenos , Isoformas de Proteínas , Proteolisis

RESUMEN

The present review explores the critical role of oxime and oxime ether moieties in enhancing the physicochemical and anticancer properties of structurally diverse molecular frameworks. Specific examples are carefully selected to illustrate the distinct contributions of these functional groups to general strategies for molecular design, modulation of biological activities, computational modeling, and structure-activity relationship studies. An extensive literature search was conducted across three databases, including PubMed, Google Scholar, and Scifinder, enabling us to create one of the most comprehensive overviews of how oximes and oxime ethers impact antitumor activities within a wide range of structural frameworks. This search focused on various combinations of keywords or their synonyms, related to the anticancer activity of oximes and oxime ethers, structure-activity relationships, mechanism of action, as well as molecular dynamics and docking studies. Each article was evaluated based on its scientific merit and the depth of the study, resulting in 268 cited references and more than 336 illustrative chemical structures carefully selected to support this analysis. As many previous reviews focus on one subclass of this extensive family of compounds, this report represents one of the rare and fully comprehensive assessments of the anticancer potential of this group of molecules across diverse molecular scaffolds.

Asunto(s)

Éter , Oximas , Oximas/farmacología , Oximas/química , Éteres/farmacología , Éteres/química , Relación Estructura-Actividad , Éteres de Etila

RESUMEN

Statins are an essential medication class in the treatment of lipid diseases because they inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. They reduce cholesterol levels and reduce the risk of cardiovascular disease in both primary and secondary prevention. In addition to their powerful pharmacologic suppression of cholesterol production, statins appear to have pleitropic effects in a wide variety of other diseases by modulating signaling pathways. In recent years, statins have seen a large increase in interest due to their putative anticancer effects. Statins appear to cause upregulation or inhibition in key pathways involved in cancer such as inhibition of proliferation, angiogenesis, and metastasis as well as reducing cancer stemness. Further, statins have been found to induce oxidative stress, cell cycle arrest, autophagy, and apoptosis of cancer cells. Interestingly, clinical studies have shown that statin use is associated with a decreased risk of cancer formation, lower cancer grade at diagnosis, reduction in the risk of local reoccurrence, and increasing survival in patients. Therefore, our objective in the present review is to summarize the findings of the publications on the underlying mechanisms of statins' anticancer effects and their clinical implications.

RESUMEN

<b>Background and Objective:</b> Liver cancer is the common cause of cancer death. <i>Paris polyphylla</i> is used as a traditional folk medicine in Vietnam to treat pneumonia, mastitis, bruises and fractures but no study was available regarding its ability to treat liver cancer or slow its growth. In this study, <i>Paris polyphylla</i> samples were identified and evaluated cytotoxic activity against the liver cancer cells. <b>Materials and Methods:</b> <i>Paris polyphylla</i> species were collected from various areas in Yen Bai, Vietnam, which were identified by comparative morphological method and DNA barcoding for the <i>18S, matK</i> genes and <i>ITS</i> region. <i>Paris polyphylla</i> samples were dried until constant weight, ground into a fine powder and extracted in various solvents. The bioactivity of these extracts were done by the MTT assay. <b>Results:</b> The sequences of <i>18S, matK</i> genes and <i>ITS</i> region were high similarity to sequences of <i>P. polyphylla</i> in the National Center for Biotechnology Information. The N-hexane and ethyl acetate fractions were produced from the methanol extract of <i>P. polyphylla</i>. The TLC results showed that there was a significant difference in the component of n-hexane and ethyl acetate fraction. The N-hexane fraction contains mainly low-polarity and non-polarity substances. While ethyl acetate fraction consists mainly of polar substances. In addition, ethyl acetate fraction was shown the strongest cytotoxic activity on the cancer cell lines HepG2 and Huh7 with the evaluation of IC₅₀ = 115.11±2.77 µg mL¹ and IC₅₀ = 148.11±1.78 µg mL¹. <b>Conclusion:</b> The extract of <i>Paris polyphylla</i> demonstrated strong potential to inhibit the growth of the liver cancer cell line. The ethyl acetate fraction has the highest ability for cytotoxicity on the liver and cell line at a concentration of 200 µg mL¹ through MTT.

Asunto(s)

Carcinoma Hepatocelular , Escarabajos , Liliaceae , Neoplasias Hepáticas , Femenino , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Extractos Vegetales/farmacología

RESUMEN

In this study, twenty-one novel 2,4-diaminopyrimidine cinnamyl derivatives as inhibitors targeting FAK were designed and synthesized based on the structure of TAE-226, and the inhibitory effects of these compounds on both the FAK enzyme and three cancer cell lines (MGC-803, HCT-116, and KYSE30) were investigated. Among them, compound 12s displayed potent inhibitory potency on FAK (IC50 = 47 nM), and demonstrated more significant antiproliferative activities in MGC-803, HCT-116 and KYSE30 cells (IC50 values were 0.24, 0.45 and 0.44 µM, respectively) compared to TAE-226. Furthermore, compound 12s significantly inhibited FAK activation leading to the negative regulation of FAK-related signaling pathways such as AKT/mTOR and MAPK signaling pathways. Molecular docking study suggested that compound 12s could well occupy the ATP-binding pocket site of FAK similar to TAE-226. In addition, compound 12s also efficiently inhibited the proliferation, induced apoptosis and cellular senescence in MGC-803 cells. In conclusion, compound 12s emerges a potent FAK inhibitor that could exert potent inhibitory activity against gastric cancer cells.

Asunto(s)

Antineoplásicos , Neoplasias Gástricas , Humanos , Relación Estructura-Actividad , Antineoplásicos/química , Simulación del Acoplamiento Molecular , Neoplasias Gástricas/tratamiento farmacológico , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas

RESUMEN

Presently, the most effective way to transport drugs specifically to mitochondria inside the cells is of pharmacophoric interest, as mitochondria are recognized as one of the most important targets for new drug design in cancer diagnosis. To date, there are many reviews covering the photophysical, photochemical, and anticancer properties of ruthenium(II) based metallodrugs owing to their high interest in biological applications. There are, however, no reviews specifically covering the mitochondria-localized luminescent Ru(II) complexes and their subsequent mitochondria-mediated anticancer activities. Therefore, this review describes the physicochemical basis for the mitochondrial accumulation of ruthenium complexes, their synthetic strategies to localize and monitor the mitochondria in living cells, and their related underlying anticancer results. Finally, we review the related areas from previous works describing the mitochondria-localized ruthenium complexes for the treatment of cancer-related diseases. Along with this, we also deliberate the perspectives and future directions for emerging more bifunctional Ru(II) complexes that can target, image, and kill tumors more efficiently in comparison with the existing mitochondria-targeted cancer therapeutics.

Asunto(s)

Antineoplásicos , Complejos de Coordinación , Neoplasias , Rutenio , Humanos , Rutenio/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/uso terapéutico , Complejos de Coordinación/química , Antineoplásicos/química , Neoplasias/tratamiento farmacológico , Mitocondrias

RESUMEN

A manganese(III) complex, [MnIII(L)(SCN)(enH)](NO3)·H2O (1•H2O) (H2L = 2-((E)-(2-((E)-2-hydroxy-3-methoxybenzylidene-amino)-ethyl-imino)methyl)-6-methoxyphenol), has been synthesized and characterized by single-crystal X-ray diffraction analysis. The interaction of 1•H2O with DNA was studied by monitoring the decrease in absorbance of the complex at λ = 324 nm with the increase in DNA concentration, providing an opportunity to determine the binding constant of the 1•H2O-ct-DNA complex as 5.63 × 103 M-1. Similarly, fluorescence titration was carried out by adding ct-DNA gradually and monitoring the increase in emission intensity at 453 nm on excitation at λex = 324 nm. A linear form of the Benesi-Hildebrand equation yields a binding constant of 4.40 × 103 M-1 at 25 °C, establishing the self-consistency of our results obtained from absorption and fluorescence titrations. The competitive displacement reactions of dyes like ethidium bromide, Hoechst, and DAPI (4',6-diamidine-2'-phenylindole dihydrochloride) from dye-ct-DNA conjugates by 1•H2O were analyzed, and the corresponding KSV values are 1.05 × 104, 1.25 × 104, and 1.35 × 104 M-1 and the Kapp values are 2.16 × 103, 8.34 × 103, and 9.0 × 103 M-1, from which it is difficult to infer the preference of groove binding over intercalation by these DNA trackers. However, the molecular docking experiments and viscosity measurement clearly indicate the preference for minor groove binding over intercalation, involving a change in Gibbs free energy of -8.56 kcal/mol. The 1•H2O complex was then evaluated for its anticancer potential in breast cancer MCF-7 cells, which severely abrogates the growth of the cells in both 2D and 3D mammospheres, indicating its promising application as an anticancer drug through a minor groove binding interaction with ct-DNA.

Asunto(s)

Complejos de Coordinación , Bases de Schiff , Humanos , Manganeso/farmacología , Manganeso/química , Simulación del Acoplamiento Molecular , Complejos de Coordinación/química , ADN/química

RESUMEN

Histone deacetylases, as a new class of anticancer targets, could maintain homeostasis by catalyzing histone deacetylation and play important roles in regulating the expression of target genes. Due to the fact that simultaneous intervention with dual tumor related targets could improve treatment effects, researches on innovative design of dual-target drugs are underway. HDAC is known as a "sensitizer" for the synergistic effects with other anticancer-target drugs because of its flexible structure design. The synergistic effects of HDAC inhibitor and other target inhibitors usually show enhanced inhibitory effects on tumor cells, and also provide new strategies to overcome multidrug resistance. Many research groups have reported that simultaneously inhibiting HDAC and other targets, such as tubulin, EGFR, could enhance the therapeutic effects. The o-aminobenzamide group is often used as a ZBG group in the design of HDAC inhibitors with potent antitumor effects. Given the prolonged inhibitory effects and reduced toxic side effects of HDAC inhibitors using o-aminobenzamide as the ZBG group, the o-aminobenzamide group is expected to become a more promising alternative to hydroxamic acid. In fact, o-aminobenzamide-based dual inhibitors of HDAC with different chemical structures have been extensively prepared and reported with synergistic and enhanced anti-tumor effects. In this work, we first time reviewed the rational design, molecular docking, inhibitory activities and potential application of o-aminobenzamide-based HDAC inhibitors with dual targeting capabilities in cancer therapy, which might provide a reference for developing new and more effective anticancer drugs.

Asunto(s)

Antineoplásicos , Neoplasias , Inhibidores de Histona Desacetilasas/química , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Antineoplásicos/química , Tubulina (Proteína) , Proliferación Celular , Neoplasias/tratamiento farmacológico

RESUMEN

A new type of fibrous mat based on a cellulose derivative-cellulose acetate (CA) or CA and water-soluble polymers (polyvinylpyrrolidone, PVP or poly(vinyl alcohol), PVA)-loaded with the model drug 5-nitro-8-hydroxyquinoline (5N) was fabricated via electrospinning or electrospinning in conjunction with electrospraying. Scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FTIR), water contact angle measurements and ultraviolet-visible spectroscopy (UV-Vis) were used for the complex characterization of the obtained novel material. The decoration of CA fibers with a water-soluble polymer containing the drug resulted in the facilitation of wetting and fast drug release. The 5N-containing fibrous material showed antioxidant activity. Moreover, the proposed materials' antibacterial and antifungal properties were tested against S. aureus, E. coli, P. aeruginosa and C. albicans. Well-distinguished, sterile zones with diameters above 3.5 cm were observed around all 5N-containing mats. The mats' cytotoxicity toward HeLa carcinoma cells and normal mouse BALB/c 3T3 fibroblasts was assessed. The 5N-in-CA, PVP,5N-on-(5N-in-CA) and PVA,5N-on-(5N-in-CA) fibrous mats possessed anticancer efficacies and much lower levels of toxicity against normal cells. Therefore, the as-created novel electrospun materials, which are based on polymers loaded with the drug 5N via electrospinning/electrospraying, can potentially be applied for topical wound healing and for local cancer therapy.

RESUMEN

Bacterial secondary metabolites are a valuable source of various molecules that have antibacterial and anticancer activity. In this study, ten endosymbiotic bacteria of aphids, aphid predators and ants were isolated. Bacterial strains were identified according to the 16S rRNA gene. Ethyl acetate fractions of methanol extract (EA-ME) were prepared from each isolated bacterium and tested for their antibacterial activities using the disk diffusion method. The EA-ME of three bacterial species, Planococcus sp., Klebsiella aerogenes, Enterococcus avium, from the pomegranate aphids Aphis punicae, Chrysoperia carnea, and Tapinoma magnum, respectively, exhibited elevated antibacterial activity against one or several of the five pathogenic bacteria tested. The inhibition zones ranged from 10.00 ± 0.13 to 20.00 ± 1.11 mm, with minimum inhibitory concentration (MIC) values ranging from 0.156 mg/mL to 1.25 mg/mL. The most notable antibacterial activity was found in the EA-ME of K. aerogenes against Klebsiella pneumonia and Escherichia coli, with an MIC value of 0.156 mg/mL. The cytotoxic activity of EA-ME was dependent on the cell line tested. The most significant cytotoxicity effect was observed for extracts of K. aerogenes and E. avium, at 12.5 µg/mL, against the epithelial cells of lung carcinoma (A549), with a cell reduction of 79.4% and 67.2%, respectively. For the EA-ME of K. aerogenes and Pantoea agglomerans at 12.5 µg/mL, 69.4% and 67.8% cell reduction were observed against human colon cancer (Hct116), respectively. Gas chromatography-mass spectrometry (GC-MS) analysis of three EA-ME revealed the presence of several bioactive secondary metabolites that have been reported previously to possess antibacterial and anticancer properties. To the best of our knowledge, this is the first study to examine the biological activities of endosymbiotic bacteria in aphids, aphid predators and ants. The promising data presented in this study may pave the way for alternative drugs to overcome the continued emergence of multidrug-resistant bacteria, and find alternative drugs to conventional cancer therapies.

Asunto(s)

Áfidos , Granada (Fruta) , Animales , Humanos , Extractos Vegetales/química , ARN Ribosómico 16S , Antibacterianos/química , Bacterias , Pruebas de Sensibilidad Microbiana

RESUMEN

Vascular epidermal growth factor receptor-2 (VEGFR-2), as an important tyrosine transmembrane protein, plays an important role in regulating endothelial cell proliferation and migration, regulating angiogenesis and other biological functions. VEGFR-2 is aberrantly expressed in many malignant tumors, and it is also related to the occurrence, development, and growth of tumors and drug resistance. Currently, there are nine VEGFR-2 targeted inhibitors approved by US.FDA for clinical use as anticancer drugs. Due to the limited clinical efficacy and potential toxicity of VEGFR inhibitors, it is necessary to develop new strategies to improve the clinical efficacy of VEGFR inhibitors. The development of multitarget therapy, especially dual-target therapy, has become a hot research field of cancer therapy, which may provide an effective strategy with higher therapeutic efficacy, pharmacokinetic advantages and low toxicity. Many groups have reported that the therapeutic effects could be improved by simultaneously inhibiting VEGFR-2 and other targets, such as EGFR, c-Met, BRAF, HDAC, etc. Therefore, VEGFR-2 inhibitors with multi-targeting capabilities have been considered to be promising and effective anticancer agents for cancer therapy. In this work, we reviewed the structure and biological functions of VEGFR-2, and summarized the drug discovery strategies, and inhibitory activities of VEGFR-2 inhibitors with multi-targeting capabilities reported in recent years. This work might provide the reference for the development of VEGFR-2 inhibitors with multi-targeting capabilities as novel anticancer agents.

Asunto(s)

Antineoplásicos , Neoplasias , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Humanos , Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Proliferación Celular , Descubrimiento de Drogas , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/química , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo