Search results for " anticancer"

Selected cytotoxic gold compounds cause significant inhibition of 20S proteasome catalytic activities

2014

Abstract Six structurally diverse cytotoxic gold compounds are reported to cause profound and differential inhibition of the three main catalytic activities of purified 20S proteasome whilst auranofin , an established gold(I) drug in clinical use, is nearly ineffective. In particular, the gold(I) complex [( pbiH ) Au ( PPh 3 )] PF 6 , turns out to be the most potent inhibitor of all three enzyme activities with sub-micromolar IC 50 values. The present results further support the view that proteasome inhibition may play a major – yet not exclusive – role in the cytotoxic actions of gold based anticancer agents.

Targeting G-quadruplex DNA as Potential Anti-cancer Therapy

2017

This chapter provides an introduction and also a review on non-canonical DNA structures such as guanine-quadruplexes (G-quadruplexes) and their targeting by small molecules for applications in Pharmacology. The articles considered in this chapter are mainly from 2016.

Antitumor effects of novel co-drugs linking histone deacetylase and ribonucleotide reductase inhibitors in hematological tumors

2011

Combination therapy is the mainstay of anticancer therapy due to the significant synergistic effects achievable. Now that anticancer drug research turned toward a more molecular targeted approach, the design of dual-target drugs appears to be a new promising strategy with the potential to improve the therapeutic efficacy of the single drug and to reduce the probability of drug induced resistance and cross resistance. In our previous work, we found that 3’-C-methyl-adenosine (3’-Me-Ado), developed by us as a potent ribonucleotide reductase (RR) inhibitor with antitumor activity against both human leukemia and carcinoma cell lines, elicited significant growth inhibitory and apoptotic synergis…

Phytochemical Profile and Antioxidant, Antiproliferative, and Antimicrobial Properties of Rubus idaeus Seed Powder

2022

In the context of the contemporary research on sustainable development and circular economy, the quest for effective strategies aimed at revaluation of waste and by-products generated in industrial and agricultural production becomes important. In this work, an ethanolic extract from red raspberry (Rubus idaeus) seed waste (WRSP) was evaluated for its phytochemical composition and functional properties in term of antioxidative, antiproliferative, and antimicrobial activities. Chemical composition of the extract was determined by both HPLC-ESI-MS/MS and spectrophotometric methods. Phytochemical analysis revealed that flavan-3-ols and flavonols were the major phenolic compounds contained in W…

SINTESI ED ATTIVITÀ ANTINEOPLASTICA DI NUOVI COMPOSTI ETEROCICLICI

2004

Synthesis, X-ray Single-Crystal Analysis, and Anticancer Activity Evaluation of New Alkylsulfanyl-Pyridazino[4,5-b]indole Compounds as Multitarget In…

2022

The alkylation of 3,5-dihydro-4H-pyridazino[4,5-b]indole-4-thione with benzyl bromide, ethyl chloroacetate, and allyl bromide in the presence of potassium carbonate (K2CO3) yielded new alkylsulfanylpyridazino[4,5-b]indole derivatives (i.e., compounds 4–6). Hydrazinolysis of ester 6 resulted in hydrazide 7. The structure of compound 6 was verified by X-ray single-crystal analysis. Among the synthesized compounds, compound 6 exhibited the most promising cytotoxicity toward MCF-7 cells with an IC50 value of 12 µM. It showed potential inhibition activity toward EGFR, PI3K, and AKT in MCF-7 cells, with 0.26-, 0.49-, and 0.31-fold reductions in concentration compared to an untreated c…

Metal drugs and the anticancer immune response

2018

The immune system deploys a multitude of innate and adaptive mechanisms not only to ward off pathogens but also to prevent malignant transformation ("immune surveillance"). Hence, a clinically apparent tumor already reflects selection for those malignant cell clones capable of evading immune recognition ("immune evasion"). Metal drugs, besides their well-investigated cytotoxic anticancer effects, massively interact with the cancer-immune interface and can reverse important aspects of immune evasion. This topic has recently gained intense attention based on combination approaches with anticancer immunotherapy (e.g., immune checkpoint inhibitors), a strategy recently delivering first exciting…

Identification of 2-(thiophen-2-yl)acetic Acid-Based Lead Compound for mPGES-1 Inhibition.

2021

We report the implementation of our in silico/synthesis pipeline by targeting the glutathione-dependent enzyme mPGES-1, a valuable macromolecular target in both cancer therapy and inflammation therapy. Specifically, by using a virtual fragment screening approach of aromatic bromides, straightforwardly modifiable by the Suzuki-Miyaura reaction, we identified 3-phenylpropanoic acid and 2-(thiophen-2-yl)acetic acid to be suitable chemical platforms to develop tighter mPGES-1 inhibitors. Among these, compounds 1c and 2c showed selective inhibitory activity against mPGES-1 in the low micromolar range in accordance with molecular modeling calculations. Moreover, 1c and 2c exhibited interesting IC…

Conjugados poliméricos y su utilización como nanomedicinas anticancerígenas

2009

Independientemente del descubrimiento de nuevos fármacos para dianas farmacológicas bien establecidas, el compromiso de la ciencia con la sociedad demanda del desarrollo de análogos macromoleculares que mejoren las posibilidades terapéuticas de los fármacos existentes aportando una mayor actividad biológica y una mayor especificidad. Se postula, cada vez con más fuerza, que la aplicación de la nanotecnología a la medicina es la clave para conseguir las mejoras necesarias tanto en diagnosis como en terapia anticancerígeno [1]. Para poder distinguirlos de otros productos biotecnológicos como proteínas y anticuerpos, los nanofármacos han sido definidos como “... sistemas complejos de escala na…

Redox imbalances in ageing and metabolic alterations: Implications in cancer and cardiac diseases. An overview from the working group of cardiotoxici…

2020

Metabolic syndrome (MetS) is a well established risk factor for cardiovascular (CV) diseases. In addition, several studies indicate that MetS correlates with the increased risk of cancer in adults. The mechanisms linking MetS and cancer are not fully understood. Several risk factors involved in MetS are also cancer risk factors, such as the consumption of high calorie-food or high fat intake, low fibre intake, and sedentary lifestyle. Other common aspects of both cancer and MetS are oxidative stress and inflammation. In addition, some anticancer treatments can induce cardiotoxicity, including, for instance, left ventricular (LV) dysfunction and heart failure (HF), endothelial dysfunction an…