scholarly journals Gold (III) Derivatives in Colon Cancer Treatment

2022 ◽  
Vol 23 (2) ◽  
pp. 724
Author(s):  
Agata Gurba ◽  
Przemysław Taciak ◽  
Mariusz Sacharczuk ◽  
Izabela Młynarczuk-Biały ◽  
Magdalena Bujalska-Zadrożny ◽  
...  

Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2505
Author(s):  
Raheem Remtulla ◽  
Sanjoy Kumar Das ◽  
Leonard A. Levin

Phosphine-borane complexes are novel chemical entities with preclinical efficacy in neuronal and ophthalmic disease models. In vitro and in vivo studies showed that the metabolites of these compounds are capable of cleaving disulfide bonds implicated in the downstream effects of axonal injury. A difficulty in using standard in silico methods for studying these drugs is that most computational tools are not designed for borane-containing compounds. Using in silico and machine learning methodologies, the absorption-distribution properties of these unique compounds were assessed. Features examined with in silico methods included cellular permeability, octanol-water partition coefficient, blood-brain barrier permeability, oral absorption and serum protein binding. The resultant neural networks demonstrated an appropriate level of accuracy and were comparable to existing in silico methodologies. Specifically, they were able to reliably predict pharmacokinetic features of known boron-containing compounds. These methods predicted that phosphine-borane compounds and their metabolites meet the necessary pharmacokinetic features for orally active drug candidates. This study showed that the combination of standard in silico predictive and machine learning models with neural networks is effective in predicting pharmacokinetic features of novel boron-containing compounds as neuroprotective drugs.


2013 ◽  
Vol 85 (4) ◽  
pp. 1483-1487
Author(s):  
DAVID FEDER ◽  
FABIO F. PERRAZO ◽  
EDIMAR C. PEREIRA ◽  
SILVANA FORSAIT ◽  
CECILIA K.R. FEDER ◽  
...  

In the adult organism, angiogenesis is restricted to a few physiological conditions. On the other hand, uncontrolled angiogenesis have often been associated to angiogenesis-dependent pathologies. A variety of animal models have been described to provide more quantitative analysis of in vivo angiogenesis and to characterize pro- and antiangiogenic molecules. However, it is still necessary to establish a quantitative, reproducible and specific method for studies of angiogenesis factors and inhibitors. This work aimed to standardize a method for the study of angiogenesis and to investigate the effects of thalidomide on angiogenesis. Sponges of 0.5 x 0.5 x 0.5 cm were implanted in the back of mice groups, control and experimental (thalidomide 200 mg/K/day by gavage). After seven days, the sponges were removed. The dosage of hemoglobin in sponge and in circulation was performed and the ratio between the values was tested using nonparametric Mann-Whitney test. Results have shown that sponge-induced angiogenesis quantitated by ratio between hemoglobin content in serum and in sponge is a helpful model for in vivo studies on angiogenesis. Moreover, it was observed that sponge-induced angiogenesis can be suppressed by thalidomide, corroborating to the validity of the standardized method.


2020 ◽  
Vol 21 (2) ◽  
pp. 423 ◽  
Author(s):  
Alessandro Colapietro ◽  
Andrea Mancini ◽  
Flora Vitale ◽  
Stefano Martellucci ◽  
Adriano Angelucci ◽  
...  

Over recent years, many authors discussed the effects of different natural compounds on glioblastoma (GBM). Due to its capacity to impair survival and progression of different cancer types, saffron extract (SE), named crocetin (CCT), is particularly noteworthy. In this work, we elucidated the antitumor properties of crocetin in glioma in vivo and in vitro models for the first time. The in vitro results showed that the four tumor cell lines observed in this study (U251, U87, U138, and U373), which were treated with increasing doses of crocetin, showed antiproliferative and pro-differentiative effects as demonstrated by a significant reduction in the number of viable cells, deep changes in cell morphology, and the modulation of mesenchymal and neuronal markers. Indeed, crocetin decreased the expression of Cluster of Differentiation CD44, CD90, CXCR4, and OCT3/4 mesenchymal markers, but increased the expression of βIII-Tubulin and neurofilaments (NFH) neuronal linage-related markers. Epigenetic mechanisms may modulate these changes, since Histone Deacetylase, HDAC1 and HDAC3 were downmodulated in U251 and U87 cells, whereas HDAC1 expression was downmodulated in U138 and U373 cells. Western blotting analyses of Fatty Acid Synthase, FASN, and CD44 resulted in effective inhibition of these markers after CCT treatment, which was associated with important activation of the apoptosis program and reduced glioma cell movement and wound repair. The in vivo studies aligned with the results obtained in vitro. Indeed, crocetin was demonstrated to inhibit the growth of U251 and U87 cells that were subcutaneously injected into animal models. In particular, the Tumor To Progression or TTP values and Kaplan–Meier curves indicated that crocetin had more major effects than radiotherapy alone, but similar effects to temozolomide (TMZ). An intra-brain cell inoculation of a small number of luciferase-transfected U251 cells provided a model that was able to recapitulate recurrence after surgical tumor removal. The results obtained from the orthotopic intra-brain model indicated that CCT treatment increased the disease-free survival (DFS) and overall survival (OS) rates, inducing a delay in appearance of a detectable bioluminescent lesion. CCT showed greater efficacy than Radio Therapy (RT) but comparable efficacy to temozolomide in xenograft models. Therefore, we aimed to continue the study of crocetin’s effects in glioma disease, focusing our attention on the radiosensitizing properties of the natural compound and highlighting the ways in which this was realized.


Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 694
Author(s):  
Solomon Abrha ◽  
Andrew Bartholomaeus ◽  
Wubshet Tesfaye ◽  
Jackson Thomas

Impetigo (school sores), a superficial skin infection commonly seen in children, is caused by the gram-positive bacteria Staphylococcus aureus and/or Streptococcus pyogenes. Antibiotic treatments, often topical, are used as the first-line therapy for impetigo. The efficacy of potential new antimicrobial compounds is first tested in in vitro studies and, if effective, followed by in vivo studies using animal models and/or humans. Animal models are critical means for investigating potential therapeutics and characterizing their safety profile prior to human trials. Although several reviews of animal models for skin infections have been published, there is a lack of a comprehensive review of animal models simulating impetigo for the selection of therapeutic drug candidates. This review critically examines the existing animal models for impetigo and their feasibility for testing the in vivo efficacy of topical treatments for impetigo and other superficial bacterial skin infections.


Blood ◽  
2009 ◽  
Vol 114 (9) ◽  
pp. 1987-1998 ◽  
Author(s):  
Tong-Young Lee ◽  
Stefan Muschal ◽  
Elke A. Pravda ◽  
Judah Folkman ◽  
Amir Abdollahi ◽  
...  

Angiostatin, a proteolytic fragment of plasminogen, is a potent endogenous antiangiogenic agent. The molecular mechanisms governing angiostatin's antiangiogenic and antitumor effects are not well understood. Here, we report the identification of mitochondrial compartment as the ultimate target of angiostatin. After internalization of angiostatin into the cell, at least 2 proteins within the mitochondria bind this molecule: malate dehydrogenase, a member of Krebs cycle, and adenosine triphosphate synthase. In vitro and in vivo studies revealed differential regulation of key prosurvival and angiogenesis-related proteins in angiostatin-treated tumors and tumor-endothelium. Angiostatin induced apoptosis via down-regulation of mitochondrial BCL-2. Angiostatin treatment led to down-regulation of c-Myc and elevated levels of another key antiangiogenic protein, thrombospondin-1, reinforcing its antitumor and antiangiogenic effects. Further evidence is provided for reduced recruitment and infiltration of bone marrow–derived macrophages in angiostatin-treated tumors. The observed effects of angiostatin were restricted to the tumor site and were not observed in other major organs of the mice, indicating unique tumor specific bioavailability. Together, our data suggest mitochondria as a novel target for antiangiogenic therapy and provide mechanistic insights to the antiangiogenic and antitumor effects of angiostatin.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Saiedeh Razi Soofiyani ◽  
Kamran Hosseini ◽  
Haleh Forouhandeh ◽  
Tohid Ghasemnejad ◽  
Vahideh Tarhriz ◽  
...  

Lymphoma is a name for malignant diseases of the lymphatic system including Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Although several approaches are used for the treatment of these diseases, some of them are not successful and have serious adverse effects. Therefore, other effective treatment methods might be interesting. Studies have indicated that plant ingredients play a key role in treating several diseases. Some plants have already shown a potential therapeutic effect on many malignant diseases. Quercetin is a flavonoid found in different plants and could be useful in the treatment of different malignant diseases. Quercetin has its antimalignant effects through targeting main survival pathways activated in tumor cells. In vitro/in vivo experimental studies have demonstrated that quercetin possesses a cytotoxic effect on lymphoid cancer cells. Regardless of the optimum results that have been obtained from both in vitro/in vivo studies, few clinical studies have analyzed the antitumor effects of quercetin in lymphoid cancers. Thus, it seems that more clinical studies should introduce quercetin as a therapeutic, alone or in combination with other chemotherapy agents. Here, in this study, we reviewed the anticancer effects of quercetin and highlighted the potential therapeutic effects of quercetin in various types of lymphoma.


Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 73
Author(s):  
Juan Luis Peñas-Fuentes ◽  
Eva Siles ◽  
Eva E. Rufino-Palomares ◽  
Amalia Pérez-Jiménez ◽  
Fernando J. Reyes-Zurita ◽  
...  

Erythrodiol (EO) is a pentacyclic triterpenic alcohol found in olive tree leaves and olive oil, and it has important effects on the health properties and quality of olive oil. In this study, we characterized the cytotoxic effects of EO on human hepatocarcinoma (HepG2) cells by studying changes in cell viability, reactive oxygen species (ROS) production, antioxidant defense systems, and the proteome. The results reveal that EO markedly decreased HepG2 cell viability without changing ROS levels. The concentrations of glutathione and NADPH were significantly reduced, with selective changes in the activity of several antioxidant enzymes: glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. Proteomic data reveal that EO led to the complete elimination or decreased abundance of 41 and 3 proteins, respectively, and the abundance of 29 proteins increased. The results of functional enrichment analysis show that important metabolic processes and the nuclear transport of mature mRNA were impaired, whereas AMP biosynthesis and cell cycle G2/M phase transition were induced. The transcription factors and miRNAs involved in this response were also identified. These potent antiproliferative effects make EO a good candidate for the further analysis of its hepatic antitumor effects in in vivo studies.


2019 ◽  
Vol 18 (26) ◽  
pp. 2230-2238 ◽  
Author(s):  
Emilio S. Petito ◽  
David J.R. Foster ◽  
Michael B. Ward ◽  
Matthew J. Sykes

Poor profiles of potential drug candidates, including pharmacokinetic properties, have been acknowledged as a significant hindrance to the development of modern therapeutics. Contemporary drug discovery and development would be incomplete without the aid of molecular modeling (in-silico) techniques, allowing the prediction of pharmacokinetic properties such as clearance, unbound fraction, volume of distribution and bioavailability. As with all models, in-silico approaches are subject to their interpretability, a trait that must be balanced with accuracy when considering the development of new methods. The best models will always require reliable data to inform them, presenting significant challenges, particularly when appropriate in-vitro or in-vivo data may be difficult or time-consuming to obtain. This article seeks to review some of the key in-silico techniques used to predict key pharmacokinetic properties and give commentary on the current and future directions of the field.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17114-17114 ◽  
Author(s):  
D. C. Chan ◽  
V. J. Chen ◽  
Z. Zhang ◽  
B. Helfrich ◽  
F. R. Hirsch ◽  
...  

17114 Background: Gemcitabine (GEM) is a deoxycytidine analog that inhibits DNA synthesis. Pemetrexed (ALIMTA, PEM) is a novel antifolate inhibiting multiple enzymes targets, including thymidylate synthase (TS). This study aimed at evaluating the antitumor effects of these antimetabolites against NSCLC and SCLC tumor models. Methods: In vitro growth inhibition (IC50) studies were done by 6-days MTT assays against a panel of 20 NSCLC and 17 SCLC cell lines. In vivo studies used only NSCLC H2122 tumor line, implanted either subcutaneously in athymic nude mice or orthotopically in athymic nude rats. Drugs were given via the ip route at the designated schedules. Results: Against NSCLC and SCLC cell lines, the averaged IC50s of GEM were 0.015 ± 0.008 μM and 0.055 ± 0.04 μM respectively. The corresponding averaged IC50s for PEM were 0.65 ± 0.2 μM and 0.091±0.018 μM respectively. When H2122 tumors reached 50–100mg, mice were treated with 10 daily doses of PEM at 100, 200 and 300 mg/kg, or three doses of GEM every 4 days at 30, 60 and 120 mg/kg. PEM delayed tumor growth by 12 to 18 days, and GEM delayed by 10 to 14 days, relative to vehicle control. Results of three combination regimens with GEM (30 mg/kg) and PEM (100 mg/kg) were: (1) GEM → PEM gave intermediate activities between the two single agents, but was toxic to animals; (2) PEM and GEM given concurrently were more active than single agents alone and delayed tumor growth by 12 days with some toxic side effects; (3) PEM → GEM was better than the single agents alone, and delayed tumor growth by ∼14 days without toxicity. Athymic nude rats bearing orthotopic H2122 tumors given PEM daily at 50, 100 and 200 mg/kg for 21 days had significantly prolonged survival, but not in a dose-dependent manner. PEM at 50 mg/kg was more effective than doses at 100 or 200 mg/kg. GEM was toxic to nude rats due to poor plasma deamination of GEM. Conclusions: In vitro, PEM was more potent against SCLC than NSCLC cell lines, but GEM had similar activities against all lung lines tested. Studies of H2122 xenografts in rodent supported PEM → GEM as the preferred sequence for the combined administration of these two drugs. [Table: see text]


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Hafiza Salaha Mahrosh ◽  
Muhammad Tanveer ◽  
Rawaba Arif ◽  
Ghulam Mustafa

The Middle East respiratory syndrome coronavirus (MERS-CoV) is the major leading cause of respiratory infections listed as blueprint of diseases by the World Health Organization. It needs immediate research in the developing countries including Saudi Arabia, South Korea, and China. Still no vaccine has been developed against MERS-CoV; therefore, an effective strategy is required to overcome the devastating outcomes of MERS. Computer-aided drug design is the effective method to find out potency of natural phytochemicals as inhibitors of MERS-CoV. In the current study, the molecular docking approach was employed to target receptor binding of CoV. A total of 150 phytochemicals were docked as ligands in this study and found that some of the phytochemicals successfully inhibited the catalytic triad of MERS-CoV. The docking results brought novel scaffolds which showed strong ligand interactions with Arg178, Arg339, His311, His230, Lys146, and Arg139 residues of the viral domains. From the top ten ligands found in this study (i.e., rosavin, betaxanthin, quercetin, citromitin, pluviatilol, digitogenin, ichangin, methyl deacetylnomilinate, kobusinol A, and cyclocalamin) based on best S -score values, two phytochemicals (i.e., pluviatilol and kobusinol A) exhibited all drug-likeness properties following the pharmacokinetic parameters which are important for bioavailability of drug-like compounds, and hence, they can serve as potential drug candidates to stop the viral load. The study revealed that these phytochemicals would serve as strong potential inhibitors and a starting point for the development of vaccines and proteases against MERS-CoV. Further, in vivo studies are needed to confirm the efficacy of these potential drug candidates.


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