Search results for "binding"
showing 10 items of 3896 documents
Pharmacogenomic and molecular docking studies on the cytotoxicity of the natural steroid wortmannin against multidrug-resistant tumor cells
2014
Wortmannin is a cytotoxic compound derived from the endophytic fungi Fusarium oxysporum, Penicillium wortmannii and Penicillium funiculosum that occurs in many plants, including medicinal herbs. The rationale to develop novel anticancer drugs is the frequent development of tumor resistance to the existing antineoplasic agents. Therefore, it is mandatory to analyze resistance mechanisms of novel drug candidates such as wortmannin as well to bring effective drugs into the clinic that have the potential to bypass or overcome resistance to established drugs and to substantially increase life span of cancer patients. In the present project, we found that P-glycoprotein-overexpressing tumor cells…
Topoisomerase II{alpha}-dependent and -independent apoptotic effects of dexrazoxane and doxorubicin.
2009
Abstract Coadministration of the iron chelator dexrazoxane reduces by 80% the incidence of heart failure in cancer patients treated with anthracyclines. The clinical application of dexrazoxane is limited, however, because its ability to inhibit topoisomerase IIα (TOP2A) is feared to adversely affect anthracycline chemotherapy, which involves TOP2A-mediated generation of DNA double-strand breaks (DSB). Here, we investigated the apoptotic effects of dexrazoxane and the anthracycline doxorubicin, alone and in combination, in a tumor cell line with conditionally regulated expression of TOP2A. Each drug caused apoptosis that was only partly dependent on TOP2A. Unexpectedly, dexrazoxane was found…
High-throughput capillary electrophoresis frontal analysis method for the study of drug interactions with human serum albumin at near-physiological c…
2004
The application of the short-end capillary injection to capillary electrophoresis frontal analysis (CE-FA) to study the interaction between basic, neutral and acid drugs towards human serum albumin (HSA) at near-physiological conditions is presented. The compounds selected display a wide range of binding affinities and the results obtained were in good agreement with those reported in the literature. An equation for the estimation of the number of primary binding sites and their corresponding affinity constants is developed isolating the experimentally measured variables in just one axis. The proposed CE-FA method to screen drug interactions with HSA under physiological conditions is simple…
A high-quality homology model for the human dopamine transporter validated for drug design purposes.
2018
The human dopamine transporter (hDAT) plays many vital functions within the central nervous system and is thus targeted by many pharmaceutical agents. Dopamine-related therapies are in current development for individuals with dopamine-related disorders including depression, Parkinson's disease, and psychostimulant addictions such as cocaine abuse. Yet, most efforts to develop new dopamine therapies are within costly structure-activity relationship studies. Through structure-based drug design techniques, the binding site of hDAT can be utilized to develop novel selective and potent dopamine therapies at reduced costs. However, no structural models of hDAT specifically validated for rational …
Characterization of basic drug–human serum protein interactions by capillary electrophoresis
2006
Drug-protein interactions are determining factors in the therapeutic, pharmacodynamic and toxicological drug properties. The affinity of drugs towards plasmatic proteins is apparently well established in bibliography. Albumin (HSA) especially binds neutral and negatively charged compounds; alpha(1)-acid glycoprotein (AGP) binds many cationic drugs, lipoproteins bind to nonionic and lipophilic drugs and some anionic drugs while globulins interact inappreciably with the majority of drugs. In this paper, the characterization of the interaction between cationic drugs, beta-blockers and phenotiazines towards HSA, AGP, and both HSA + AGP mixtures of proteins under physiological conditions by CE-f…
Covalent binding of drug metabolites to DNA ? a tool of predictive value?
1980
The presently available data suggest at least some correlation between covalent binding of drug metabolites to DNA and carcinogenicity of that drug. More data, however, are needed to establish the predictability of covalent DNA binding assays for extrahepatic cancer. A covalent binding assay requires administration of radioactively labelled compound to the experimental animals; the availability of labelled compound and requirements as to radiochemical purity, chemical and biochemical stability are limiting the applicability of this procedure. Many technical pitfalls accompany covalent DNA binding assays. It is concluded that at the present time DNA binding assays do not represent routine pr…
The broad-spectrum antiinfective drug artesunate interferes with the canonical nuclear factor kappa B (NF-κB) pathway by targeting RelA/p65.
2015
Infection with human cytomegalovirus (HCMV) is a serious medical problem, particularly in immunocompromised individuals and neonates. The success of standard antiviral therapy is hampered by low drug compatibility and induction of viral resistance. A novel strategy is based on the exploitation of cell-directed signaling inhibitors. The broad antiinfective drug artesunate (ART) offers additional therapeutic options such as oral bioavailability and low levels of toxic side-effects. Here, novel ART-derived compounds including dimers and trimers were synthesized showing further improvements over the parental drug. Antiviral activity and mechanistic aspects were determined leading to the followi…
Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection
2021
The identification of chemical compounds able to bind specific sites of the human/viral proteins involved in the SARS-CoV-2 infection cycle is a prerequisite to design effective antiviral drugs. Here we conduct a molecular dynamics study with the aim to assess the interactions of ivermectin, an antiparasitic drug with broad-spectrum antiviral activity, with the human Angiotensin-Converting Enzyme 2 (ACE2), the viral 3CLpro and PLpro proteases, and the viral SARS Unique Domain (SUD). The drug/target interactions have been characterized in silico by describing the nature of the non-covalent interactions found and by measuring the extent of their time duration along the MD simulation. Results …
Species-dependent stereospecific serum protein binding of the oral anticoagulant drug phenprocoumon
1978
13 mammalian species are classified into 3 clearcut groups with respect to the stereospecific serum protein-binding of phenprocoumon: 2 groups showing opposed stereospecific binding characteristics and a 3rd group exhibiting no stereospecific binding. Structural differences in the albumin molecule account for these stereospecific differences in serum protein-binding.
Frontiers of metal-coordinating drug design
2020
INTRODUCTION: The occurrence of metal ions in biomolecules is required to exert vital cellular functions. Metal-containing biomolecules can be modulated by small-molecule inhibitors targeting their metal-moiety. As well, the discovery of cisplatin ushered the rational discovery of metal-containing-drugs. The use of both drug types exploiting metal–ligand interactions is well established to treat distinct pathologies. Therefore, characterizing and leveraging metal-coordinating drugs is a pivotal, yet challenging, part of medicinal chemistry. AREA COVERED: Atomic-level simulations are increasingly employed to overcome the challenges met by traditional drug-discovery approaches and to compleme…