"Drug liking" from_date:2012

Synthesis, molecular docking analysis, molecular dynamic simulation, ADMET, DFT, and drug likeness studies: Novel Indeno[1,2-b]pyrrol-4(1H)-one as SARS-CoV-2 main protease inhibitors. The COVID-19 pandemic began in 2019 as a result of the advent of a novel coronavirus, SARS-CoV-2. At present, there are a limited number of approved antiviral agents for the treatment of COVID-19. Remdesivir of SARS-CoV-2. The results of the docking analysis revealed that the synthesized compounds exhibited favorable inhibitory effects. Notably, compound 5f demonstrated the highest effectiveness against the target protein. Furthermore, the pharmacokinetic and drug-like properties of the synthesized derivatives of 2-arylamino-dihydroindeno[1,2-b] pyrrol-4(1H)-one indicated their potential as promising

Identification of drug-like molecules targeting the ATPase activity of dynamin-like EHD4. Eps15 (epidermal growth factor receptor pathway substrate 15) homology domain-containing proteins (EHDs) comprise a family of eukaryotic dynamin-related ATPases that participate in various endocytic membrane trafficking pathways. Dysregulation of EHDs function has been implicated in various diseases , including cancer. The lack of small molecule inhibitors which acutely target individual EHD members has hampered progress in dissecting their detailed cellular membrane trafficking pathways and their function during disease. Here, we established a Malachite green-based assay compatible with high throughput screening to monitor the liposome-stimulated ATPase of EHD4. In this way, we identified a drug-like

Synthesis, molecular docking study, MD simulation, ADMET, and drug likeness of new thiazolo[3,2-a]pyridine-6,8-dicarbonitrile derivatives as potential anti-diabetic agents. There are numerous uses for the pharmacological effects of thiazolo-pyridine and its derivatives. The main objective of the study was to synthesis 10 novel derivatives of thiazolo[3,2-a] pyridine-6,8-dicarbonitrile with a 22 , Leu237, His299, Asp300, and His305. Moreover, the pharmacokinetic and drug-like properties of the synthesized derivatives of 2-arylamino-dihydroindeno[1,2-b] pyrrol-4(1H)-one suggest that they have the potential to be effective inhibitors of α-amylase and should be considered for further research. Nevertheless, it is crucial to ascertain the in vivo and in vitro effectiveness of these compounds through

HPLC-ESI-QTOF-MS Profiling of Antibacterial Bioactive Solvent Fractions of Senna alata (L.) Roxb (Fabaceae) Leaves, and in Silico Prediction of Pharmacokinetic, Drug-likeness, and Toxicity of Major Phyto-components. Medicinal plants are a rich source of new antibacterial leads. One such plant is Senna alata (L.) Roxb (Fabaceae), a valuable medicinal tree known in folk medicine for its metabolites in the most active fractions. In addition, the pharmacokinetic (PK) properties, drug-likeness, and medicinal chemistry of the key phytoconstituents were predicted in silico using SwissADME. Moreover, we utilized the ProTox-II web server to predict the toxicity profile of the potential drug candidates. The herbal fractions, except for the water fraction, showed remarkable antibacterial activity

'I couldn't carry on taking a drug like that': a qualitative study of patient perspectives on side effects from rheumatology drugs. There is growing interest in collecting outcome information directly from patients in clinical trials. This study evaluates what patients with rheumatic and musculoskeletal diseases (RMDs) consider important to know about symptomatic side effects they may experience

Pharmacokinetic-pharmacodynamic analysis of drug liking blockade by buprenorphine subcutaneous depot (CAM2038) in participants with opioid use disorder. Buprenorphine is used to treat opioid use disorder (OUD). Weekly and monthly subcutaneous long-acting buprenorphine injections (CAM2038) provide more stable buprenorphine plasma levels and reduce the treatment burden, misuse, and diversion associated with sublingual transmucosal buprenorphine formulations. To characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship, a maximum inhibition (I) model was developed relating CAM2038 buprenorphine plasma concentration to drug liking maximum effect (E) visual analog scale (VAS; bipolar) score after intramuscular hydromorphone administration. Data included time-matched observations

Anti-Shigella and antioxidant-based screening of some Cameroonian medicinal plants, UHPLC-LIT-MS/MS fingerprints, and prediction of pharmacokinetic and drug-likeness properties of identified chemicals. Shigella infection is a public health problem responsible for approximately 700,000 deaths annually. The management of this disease is impaired by the emergence of multidrug-resistant Shigella

Comparative effectiveness of adding delamanid to a multidrug-resistant tuberculosis regimen comprised of three drugs likely to be effective. Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and Phase III randomized controlled trial results. The Phase IIb trial found that the addition of delamanid to a background regimen

Challenging the Drug-Likeness Dogma for New Drug Discovery in Tuberculosis The emergence of multi- and extensively drug resistant tuberculosis worldwide poses a great threat to human health and highlight the need to discover and develop new, effective and inexpensive antituberculosis agents. High-throughput screening assays against well-validated drug targets and structure based drug design have drug-likeness and avoid attritions in the drug discovery process. In this review, we describe how antituberculosis compounds challenge established rules such as the Lipinski's "rule of five" and how medicinal chemistry for antituberculosis compounds must be thought beyond such dogmatic schemes.

Challenges in the use of atomistic simulations to predict solubilities of drug-like molecules Solubility is a physical property of high importance to the pharmaceutical industry, the prediction of which for potential drugs has so far been a hard task. We attempted to predict the solubility of acetylsalicylic acid (ASA) by estimating the absolute chemical potentials of its most stable polymorph values could be obtained with a better energy model; however, it seems likely computational cost may remain a limiting factor for use of this particular approach to solubility estimation.     Solubility prediction of drug-like solids remains computationally challenging, and it appears that both the underlying energy model and the computational approach applied may need improvement before the approach

Drug liking and wanting, not impulsive action or reflection is increased by 4-fluoroamphetamine New psychoactive substances (NPS) are chemical analogues designed to mimic the effects of various classic recreational drugs of abuse including MDMA, LSD, and cannabis. NPS use is associated with concern about the acute and longer-term effects particular substances might have, with abuse and addiction as potential consequences. Impulsivity and sensitivity to the rewarding effects of drugs have been considered as risk factors for drug abuse. In light of the popularity of 4-fluoroamphetamine (4-FA), it is important to assess whether 4-FA can lead to subjective drug liking and wanting, and impulsive behavior, all factors contributing to the abuse likelihood of a substance. A placebo-controlled 2-way

Methylglucosylation of aromatic amino and phenolic moieties of drug-like biosynthons by combinatorial biosynthesis Glycosylation is a prominent strategy to optimize the pharmacokinetic and pharmacodynamic properties of drug-like small-molecule scaffolds by modulating their solubility, stability, bioavailability, and bioactivity. Glycosyltransferases applicable for "sugarcoating" various small a methylglucosylation functional module in the ascomycetous fungus The GT is the founding member of a family nonorthologous to characterized fungal enzymes. Using combinatorial biosynthetic and biocatalytic platforms, we reveal that this GT is a promiscuous enzyme that efficiently modifies a broad range of drug-like substrates, including polyketides, anthraquinones, flavonoids, and naphthalenes. It yields both

Protection Against Arthritis by the Parasitic Worm Product ES-62, and Its Drug-Like Small Molecule Analogues, Is Associated With Inhibition of Osteoclastogenesis The immunomodulatory actions of parasitic helminth excretory-secretory (ES) products that serendipitously protect against development of chronic inflammatory disorders are well established: however, knowledge of the interaction between ES products and the host musculoskeletal system in such diseases is limited. In this study, we have focused on ES-62, a glycoprotein secreted by the rodent filarial nematode that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties, and also two synthetic drug-like PC-based small molecule analogues (SMAs) that mimic ES-62's immunomodulatory activity. We have

Data Mining and Machine Learning Models for Predicting Drug Likeness and Their Disease or Organ Category Data mining approaches can uncover underlying patterns in chemical and pharmacological property space decisive for drug discovery and development. Two of the most common approaches are visualization and machine learning methods. Visualization methods use dimensionality reduction techniques , and helpfully provide classification of compounds based on such features or in case of visualization methods uncover underlying patterns in the feature space. Drug-likeness has been studied from several viewpoints, but here we provide the first implementation in chemoinformatics of the t-Distributed Stochastic Neighbor Embedding (t-SNE) method for the visualization and the representation of chemical space

Optimized Lennard-Jones Parameters for Drug-Like Small Molecules Meaningful efforts in computer-aided drug design (CADD) require accurate molecular mechanical force fields to quantitatively characterize protein-ligand interactions, ligand hydration free energies, and other ligand physical properties. Atomic models of new compounds are commonly generated by analogy from the predefined tabulated

Principles for targeting RNA with drug-like small molecules. RNA molecules are essential for cellular information transfer and gene regulation, and RNAs have been implicated in many human diseases. Messenger and non-coding RNAs contain highly structured elements, and evidence suggests that many of these structures are important for function. Targeting these RNAs with small molecules offers properties of drug-like small molecules could then enable small-molecule drug discovery for RNA targets to become (only) roughly as difficult as for protein targets.

Drug-likeness prediction of chemical constituents isolated from Chinese materia medica Ciwujia. Ciwujia (CWJ), one of the most commonly used Chinese materia medicas (CMMs), is derived from the roots, rhizomes, and stems of Acanthopanax senticosus harms (AS). CWJ has been used for the treatment of various central nervous system (CNS) and peripheral system diseases. Drug-likeness prediction can targets. Additionally, 17/39 compounds had 53 structurally similar toxins and 126 potential toxicity targets. Our study suggests that these compounds have a certain drug-likeness potentials, which are also likely to be the material bases of CWJ. These results may provide a reference for the safe use of CWJ and the expansion of its application scope.

N2O strongly prevents adhesion formation and postoperative pain in open surgery through a drug-like effect Microsurgical tenets and peritoneal conditioning during laparoscopic surgery (LS) decrease postoperative adhesions and pain. For a trial in human, the strong beneficial effects of NO needed to be confirmed in open surgery (OS). In a mouse model for OS, the effect of the gas environment upon  + 4%O. Adhesions increased with the duration of exposure to CO ( < 0.0001) and decreased slightly by humidification or by the addition of 4% O. NO strongly decreased adhesions at concentrations of 5% or greater. With humidified CO + 10% NO, adhesion formation was similar in OS and LS. The drug-like and strong beneficial effect of low concentrations of NO is confirmed in OS.

Recent advances in understanding NRF2 as a druggable target: development of pro-electrophilic and non-covalent NRF2 activators to overcome systemic side effects of electrophilic drugs like dimethyl fumarate Dimethyl fumarate (DMF) is an electrophilic compound previously called BG-12 and marketed under the name Tecfidera . It was approved in 2013 by the US Food and Drug Administration

Large-Scale Structural Characterization of Drug and Drug-Like Compounds by High-Throughput Ion Mobility-Mass Spectrometry Ion mobility-mass spectrometry (IM-MS) can provide orthogonal information, i.e., m/z and collision cross section (CCS), for the identification of drugs and drug metabolites. However, only a small number of CCS values are available for drugs, which limits the use of CCS as an identification parameter and the assessment of structure-function relationships of drugs using IM-MS. Here, we report the development of a rapid workflow for the measurement of CCS values of a large number of drug or drug-like molecules in nitrogen on the widely available traveling wave IM-MS (TWIM-MS) platform. Using a combination of small molecule and polypeptide CCS calibrants, we successfully determined