Search results for "anticancer agents"
showing 10 items of 19 documents
[Au(9-methylcaffein-8-ylidene) 2 ] + /DNA Tel23 System: Solution, Computational, and Biological Studies
2017
International audience; Physicochemical methods have been used to investigate interactions occurring in solution between the dicarbene gold(I) complex [Au(9‐methylcaffein‐8‐ylidene)2]BF4 (AuNHC) and a human telomeric DNA sequence, namely Tel23. Circular dichroism measurements allow identification of the conformational changes experienced by Tel23 upon interaction with AuNHC, and the respective binding stoichiometries and constants were determined. Computational studies provide a good link between previous crystallographic results of the same system and the present solution data, offering an exhaustive description of the inherent noncovalent metallodrug–DNA interactions. Remarkably, we found…
Kinase Inhibitors in Multitargeted Cancer Therapy
2017
The old-fashioned anticancer approaches, aiming in arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled at various levels by modulation of several targets. Although at present, combinations of individual single-target drugs represent the most clinically practiced therapeutic approaches, the modulation of multiple proteins by a single drug, in accordance with the polypharmacological strategy, has become more and more appealing. In the perspective of…
Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold(I) Complex to a Telomeric DNA G-Quadruplex: a Joint ESI MS and XRD Investi…
2016
International audience; The dicarbene gold(I) complex [Au(9-methylcaffein-8-ylidene)(2)]BF4 is an exceptional organometallic compound of profound interest as a prospective anticancer agent. This gold(I) complex was previously reported to be highly cytotoxic toward various cancer cell lines invitro and behaves as a selective G-quadruplex stabilizer. Interactions of the gold complex with various telomeric DNA models have been analyzed by a combined ESI MS and X-ray diffraction (XRD) approach. ESI MS measurements confirmed formation of stable adducts between the intact gold(I) complex and Tel 23 DNA sequence. The crystal structure of the adduct formed between [Au(9-methylcaffein-8-ylidene)(2)]…
Eight-Membered Rings With Two Heteroatoms 1,2
2022
The chapter titled “Eight-membered Rings with two Heteroatoms 1,2” deals with heterocine rings with two heteroatoms in a 1,2 relationship, namely 1,2-diazocine, 2H-1,2-oxazocine, 2H-1,2-thiazocine, 1,2-dioxocin, 1,2-oxathiocin and 1,2-dithiocin. This article covers the literature from 2007 to 2019 and reports the chemistry of uncondensed derivatives, heterocines fused to carbocycles and heterocycles, as well as bridged heterocines. As usual, in the case that a particular section is not mentioned, it means that no chemistry has been reported. In this article, the “Biosynthesis” paragraph was additionally introduced, since in the latest years the contribution of Nature to the synthesis of dih…
Eight-Membered Rings With Two Heteroatoms 1,3
2022
Eight-membered rings with two heteroatoms in a 1,3-relationship, namely 1,3-diazocine, 2H-1,3-oxazocine, 2H-1,3-thiazocine, 4H-1,3-dioxocin, 4H-1,3-oxathiocin, and 4H-1,3-dithiocin, are discussed in this chapter, that covers the literature from 2007 to October 2020 (SciFindern search) and reports the chemistry of uncondensed derivatives, heterocines fused to carbocycles and heterocycles, as well as bridged heterocines. Among eight-membered 1,3-diheterocines, 1,3-diazocines and 1,3-oxazocines are the two largest classes, based on the number of publications, mostly due to the studies of the synthesis of these cyclic systems, their pharmacological properties and/or their important industrial a…
DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents.
2019
Dihydrofolate reductase inhibitors are an important class of drugs, as evidenced by their use as antibacterial, antimalarial, antifungal, and anticancer agents. Progress in understanding the biochemical basis of mechanisms responsible for enzyme selectivity and antiproliferative effects has renewed the interest in antifolates for cancer chemotherapy and prompted the medicinal chemistry community to develop novel and selective human DHFR inhibitors, thus leading to a new generation of DHFR inhibitors. This work summarizes the mechanism of action, chemical, and anticancer profile of the DHFR inhibitors discovered in the last six years. New strategies in DHFR drug discovery are also provided, …
Development of trackable metal-based drugs: new generation of therapeutic agents
2016
International audience; In medicinal chemistry, the aim is not only to conceive ever more efficient molecules, but also to understand their mechanism of action. In very recent years, a new promising strategy was developed to tackle this issue: the conception of trackable therapeutic agents. Metal-based drugs are ideal to exploit this expanding area of research.
Eight-Membered Rings With Two Heteroatoms 1,5
2022
This chapter titled “Eight-membered Rings with two Heteroatoms 1,5” deals eight-membered rings with two heteroatoms in a 1,5-relationship, namely 1,5-diazocine, 1,5-oxazocine, 1,5-thiazocine, 1,5-dioxocin, 1,5-oxathiocin, and 1,5-dithiocin and covers the literature from 2007 to October 2020 (SciFindern search) reporting the chemistry of uncondensed derivatives, diheterocines fused to carbocycles and heterocycles, as well as bridged diheterocines. Among them, the 1,5-diazocine ring system is by far the largest class, based on the number of publications which constituted the 87% of the total amount of the references reported in the range of interest of CHEC IV. Thus, 1,5-diazocines were divid…
Arylpyridines, arylpyrimidines and related compounds as potential modulator agents of the VEGF, hTERT and c-Myc oncogenes.
2019
Twenty-four derivatives structurally related to honokiol have been synthesized and biologically evaluated. IC50 values were determined towards the HT-29, MCF-7 and HEK-293 cell lines. Some of these derivatives exhibited comparable or lower IC50 values than honokiol towards the HT-29 and MCF-7 cell lines or else higher selectivity indexes than the natural product. Twelve selected derivatives were evaluated for their ability to inhibit the expression of the VEGFA, hTERT and c-Myc genes and also to inhibit the production of total c-Myc protein and the secretion of the VEGF protein. One of the most promising compounds, 3-(2,4-dimethoxyphenyl)pyridine, may be a good candidate for further studies…
Multinuclear Cytotoxic Metallodrugs: Physicochemical Characterization and Biological Properties of Novel Heteronuclear Gold-Titanium Complexes
2011
An unprecedented series of titanocene-gold bi- and trimetallic complexes of the general formula [[(η(5)-C(5)H(5))(μ-η(5):κ(1)-C(5)H(4)(CH(2))(n)PPh(2))TiCl(2)](m)AuCl(x)](q+) (n = 0, 2, or 4; m = 1, x = 1, q = 0 or m = 2, x = 0, q = 1) have been prepared and characterized spectroscopically. The luminescence spectroscopy and photophysics of one of the compounds, [[(η(5)-C(5)H(5))(μ-η(5):κ(1)-C(5)H(4)PPh(2))TiCl(2)](2)Au]PF(6), have been investigated in 2MeTHF solution and in the solid state at 77 and 298 K. Evidence for interfragment interactions based on the comparison of electronic band positions and emission lifetimes, namely, triplet energy transfer (ET) from the Au- to the Ti-containing…