Multicomponent syntheses enable the discovery of novel quisinostat-derived chemotypes as histone deacetylase inhibitors.

In this study, we synthesized and evaluated novel histone deacetylase (HDAC) inhibitors derived from the clinical candidate quisinostat. A library of 16 compounds categorized in three novel chemotypes was rapidly generated using multicomponent reactions (MCRs), enabling efficient structure-activity relationship studies. First, the compounds were evaluated for their activity against the Plasmodium falciparum strains 3D7 and Dd2, the main malaria-causing parasite, identifying compound 18b of the type C series as the most potent.

Development of peptoid-based heteroaryl-decorated histone deacetylase (HDAC) inhibitors with dual-stage antiplasmodial activity.

Dynamics of epigenetic modifications such as acetylation and deacetylation of histone proteins have been shown to be crucial for the life cycle development and survival of Plasmodium falciparum, the deadliest malaria parasite. In this study, we present a novel series of peptoid-based histone deacetylase (HDAC) inhibitors incorporating nitrogen-containing bicyclic heteroaryl residues as a new generation of antiplasmodial peptoid-based HDAC inhibitors. We synthesized the HDAC inhibitors by an efficient multicomponent protocol based on the Ugi four-component reaction.

Enhanced protein adsorption upon bulk phase separation.

In all areas related to protein adsorption, from medicine to biotechnology to heterogeneous nucleation, the question about its dominant forces and control arises. In this study, we used ellipsometry and quartz-crystal microbalance with dissipation (QCM-D), as well as density-functional theory (DFT) to obtain insight into the mechanism behind a wetting transition of a protein solution. We established that using multivalent ions in a net negatively charged globular protein solution (BSA) can either cause simple adsorption on a negatively charged interface, or a (diverging) wetting layer when approaching liquid-liquid phase separation (LLPS) by changing protein concentration (c) or temperature (T).

Remnants of the disappearing critical point in chain-forming patchy fluids.

For a standard model of patchy colloidal fluids with patch number M = 2, where chain formation (polymerization) occurs, we show that Wertheim theory predicts critical behavior at vanishing density and temperature. The analysis is based on determining lines in the phase diagram of maximal correlation length and compressibility. Simulation studies identify the latter line and confirm our prediction of Fisher-Widom crossover, i.

Bulk structural information from density functionals for patchy particles.

We investigate bulk structural properties of tetravalent associating particles within the framework of classical density functional theory, building upon Wertheim's thermodynamic perturbation theory. To this end, we calculate density profiles within an effective test-particle geometry and compare to radial distribution functions obtained from computer simulations. We demonstrate that a modified version of the functional proposed by Yu and Wu [J.

Nonequilibrium phase transitions of sheared colloidal microphases: Results from dynamical density functional theory.

By means of classical density functional theory and its dynamical extension, we consider a colloidal fluid with spherically symmetric competing interactions, which are well known to exhibit a rich bulk phase behavior. This includes complex three-dimensional periodically ordered cluster phases such as lamellae, two-dimensional hexagonally packed cylinders, gyroid structures, or spherical micelles. While the bulk phase behavior has been studied extensively in earlier work, in this paper we focus on such structures confined between planar repulsive walls under shear flow.

Phase behavior and bulk structural properties of a microphase former with anisotropic competing interactions: A density functional theory study.

Using classical density functional theory, we investigate systems exhibiting interactions where a short-range anisotropic attractive force competes with a long-range spherically symmetric repulsive force. The former is modelled within Wertheim's first-order perturbation theory for patchy particles, and the repulsive part is assumed to be a Yukawa potential which is taken into account via a mean-field approximation. From previous studies of systems with spherically symmetric competing interactions, it is well known that such systems can exhibit stable bulk cluster phases (microphase separation) provided that the repulsion is sufficiently weak compared to the attraction.

Massively parallel GPU-accelerated minimization of classical density functional theory.

In this paper, we discuss the ability to numerically minimize the grand potential of hard disks in two-dimensional and of hard spheres in three-dimensional space within the framework of classical density functional and fundamental measure theory on modern graphics cards. Our main finding is that a massively parallel minimization leads to an enormous performance gain in comparison to standard sequential minimization schemes. Furthermore, the results indicate that in complex multi-dimensional situations, a heavy parallel minimization of the grand potential seems to be mandatory in order to reach a reasonable balance between accuracy and computational cost.

Structural relaxation and diffusion in a model colloid-polymer mixture: dynamical density functional theory and simulation.

Within the Asakura-Oosawa model, we study structural relaxation in mixtures of colloids and polymers subject to Brownian motion in the overdamped limit. We obtain the time evolution of the self and distinct parts of the van Hove distribution function G(r,t) by means of dynamical density functional theory (DDFT) using an accurate free-energy functional based on Rosenfeld's fundamental measure theory. In order to remove unphysical interactions within the self part, we extend the recently proposed quenched functional framework (Stopper et al 2015 J.

Communication: Dynamical density functional theory for dense suspensions of colloidal hard spheres.

We study structural relaxation of colloidal hard spheres undergoing Brownian motion using dynamical density functional theory. Contrary to the partial linearization route [D. Stopper et al.