Search results for "combinatorial"

A loopless algorithm for generating the permutations of a multiset

2003

AbstractMany combinatorial structures can be constructed from simpler components. For example, a permutation can be constructed from cycles, or a Motzkin word from a Dyck word and a combination. In this paper we present a constructor for combinatorial structures, called shuffle on trajectories (defined previously in a non-combinatorial context), and we show how this constructor enables us to obtain a new loopless generating algorithm for multiset permutations from similar results for simpler objects.

Protocol for rational design of covalently interacting inhibitors.

2014

The inhibition potencies of covalent inhibitors mainly result from the formation of a covalent bond to the enzyme during the inhibition mechanism. This class of inhibitors has essentially been ignored in previous target-directed drug discovery projects because of concerns about possible side effects. However, their advantages, such as higher binding energies and longer drug-target residence times moved them into the focus of recent investigations. While the rational design of non-covalent inhibitors became standard the corresponding design of covalent inhibitors is still in its early stages. Potent covalent inhibitors can be retrieved from large compound libraries by covalent docking approa…

Thiazoles, Their Benzofused Systems, and Thiazolidinone Derivatives: Versatile and Promising Tools to Combat Antibiotic Resistance.

2020

Thiazoles, their benzofused systems, and thiazolidinone derivatives are widely recognized as nuclei of great value for obtaining molecules with various biological activities, including analgesic, anti-inflammatory, anti-HIV, antidiabetic, antitumor, and antimicrobial. In particular, in the past decade, many compounds bearing these heterocycles have been studied for their promising antibacterial properties due to their action on different microbial targets. Here we assess the recent development of this class of compounds to address mechanisms underlying antibiotic resistance at both bacterial-cell and community levels (biofilms). We also explore the SAR and the prospective clinical applicati…

Core-Shell Arginine-Containing Chitosan Microparticles for Enhanced Transcorneal Permeation of Drugs

2019

Chitosan oligosaccharide (C) was functionalized with L-arginine (A) and short hydrocarbon chains (C-8) to design an amphiphilic copolymer, henceforth CAC(8), leading to microparticles (MPs) consisting of an arginine-decorated hydrophilic shell and inner hydrophobic domains allowing the encapsulation of high amount hydrophobic drugs such as sorafenib tosylate (>10% w/w). L-arginine side chains were selected in order to impart the final MPs enhanced transcorneal penetration properties, thus overcoming the typical biological barriers which hamper the absorption of drugs upon topical ocular administration. The mucoadhesive properties and drug release profile of the CAC(8) MPs (CAC(8)-MPs) were …

Improving Pattern Recognition Based Pharmacological Drug Selection Through ROC Analysis

2004

The design of new medical drugs is a very complex process in which combinatorial chemistry techniques are used. The goal consists of discriminating between molecular compounds exhibiting or not certain pharmacological activities. Different machine learning approaches have been recently applied to different drug design problems leading to competitive results in pointing at particular compounds with high probability of exhibiting activity. The present work first deeps into the natural trade-off between accuracy in the much less populated active group and false alarm rate which could lead to too many expensive laboratory tests. Preliminary results show how different classification techniques a…

ChemInform Abstract: Antitumor Drug Design: DNA-Binding Ligands, Which Inhibit the Topoisomerase I

2010

Mesoporous silicate as matrix for drug delivery systems of non-steroidal antinflammatory drugs

2002

Publisher Summary The suitability of a mesoporous silicate matrix as a drug-delivery system has been evaluated using different nonsteroid anti-inflammatory agents as model drugs. This type of matrix can trap the bioactive agents by a soaking procedure and then release them in conditions mimicking the biological fluids. The high affinity of these matrices for water makes them potentially biocompatible. A matrix impregnated with diflunisal can offer a good potential as a system for the controlled drug release. In fact, only 20% of the drug is released at the gastric level allowing, in this way, the reduction of side effects related to the oral administration of nonsteroidal anti-inflammatory …

Highly convergent total synthesis of (+)-anaferine and (−)-dihydrocuscohygrine

2019

A unified and highly convergent total synthesis of anaferine and dihydrocuscohygrine alkaloids has been devised, taking advantage of the dual role of N-sulfinyl amines as nucleophilic nitrogen sources and chiral auxiliaries. A bidirectional cross metathesis reaction followed by a double intramolecular aza-Michael reaction led us to create the whole skeleton of the natural products in a very simple manner.

Hub-Centered Gene Network Reconstruction Using Automatic Relevance Determination

2012

Network inference deals with the reconstruction of biological networks from experimental data. A variety of different reverse engineering techniques are available; they differ in the underlying assumptions and mathematical models used. One common problem for all approaches stems from the complexity of the task, due to the combinatorial explosion of different network topologies for increasing network size. To handle this problem, constraints are frequently used, for example on the node degree, number of edges, or constraints on regulation functions between network components. We propose to exploit topological considerations in the inference of gene regulatory networks. Such systems are often…

Longest Common Subsequence from Fragments via Sparse Dynamic Programming

1998

Sparse Dynamic Programming has emerged as an essential tool for the design of efficient algorithms for optimization problems coming from such diverse areas as Computer Science, Computational Biology and Speech Recognition [7,11,15]. We provide a new Sparse Dynamic Programming technique that extends the Hunt-Szymanski [2,9,8] paradigm for the computation of the Longest Common Subsequence (LCS) and apply it to solve the LCS from Fragments problem: given a pair of strings X and Y (of length n and m, resp.) and a set M of matching substrings of X and Y, find the longest common subsequence based only on the symbol correspondences induced by the substrings. This problem arises in an application t…