395 Results Found

Small-molecule probes are powerful tools for studying biological systems and can serve as lead compounds for developing new therapeutics. Especially, nitrogen heterocycles are of considerable importance in the pharmaceutical field. These compounds ar...

There is an urgent need to identify efficient antiviral compounds to combat existing and emerging RNA virus infections, particularly those related to seasonal and pandemic influenza outbreaks. While inhibitors of the influenza viral integral membrane...

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a critical member of a signaling cascade that influences disease-relevant neural functions such as neural growth and plasticity. The effector domain (ED) of MARCKS interacts with the extracell...

Cell adhesion molecule L1 is a cell surface glycoprotein that promotes neuronal cell migration, fosters regeneration after spinal cord injury and ameliorates the consequences of neuronal degeneration in mouse and zebrafish models. Counter-indicative...

Experimental screening of large sets of compounds against macromolecular targets is a key strategy to identify novel bioactivities. However, large-scale screening requires substantial experimental resources and is time-consuming and challenging. Ther...

Our previous work has described a library of thioxanthones designed to have dual activity as P-glycoprotein modulators and antitumor agents. Some of these compounds had shown a significant cell growth inhibitory activity towards leukemia cell lines,...

Specific adhesion of P. falciparum parasite-infected erythrocytes (IE) in deep vascular beds can result in severe complications, such as cerebral malaria, placental malaria, respiratory distress, and severe anemia. Cerebral malaria and severe malaria...

Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibit...

The screening of more than 30 million compounds derived from 81 small molecule libraries built on 81 distinct scaffolds identified pyrrolidine bis-cyclic guanidine library (TPI-1955) to be one of the most active and selective antiplasmodial libraries...

Background/Objective: Immunomodulators play a critical role in regulating immune responses, with immunostimulatory agents enhancing cancer therapy by activating immune cells such as T cells. While immune checkpoint inhibitors (ICIs) targeting PD-1 an...

Flow chemistry has gained considerable recognition as a simple, efficient, and safe technology for the synthesis of many types of organic and inorganic molecules ranging in scope from large complex natural products to silicon nanoparticles. In this p...

The large originator pharmaceutical companies need more and more new compounds for their molecule banks, because high throughput screening (HTS) is still a widely used method to find new hits in the course of the lead discovery. In the design and syn...

The human fungal pathogen Candida albicans can form biofilms on biotic and abiotic surfaces, which are inherently resistant to antifungal drugs. We screened the Chembridge Small Molecule Diversity library containing 30,000 “drug-like” sma...

The imidazole-4,5-dicarboxylic acid scaffold is readily derivatized with amino acid esters and alkanamines to afford compounds with intramolecularly hydrogen bonded conformations that mimic substituted purines and therefore are hypothesized to be pot...

Predicting antitumor activity of compounds using regression models trained on a small number of compounds with measured biological activity is an ill-posed inverse problem. Yet, it occurs very often within the academic community. To counteract, up to...

Considering the potential bioactivities of natural product and natural product-like compounds with highly complex and diverse structures, the screening of collections and small-molecule libraries for high-throughput screening (HTS) and high-content s...

The imidazole-4,5-dicarboxylic acid scaffold is readily derivatized with amino acid esters to afford symmetrically- and dissymmetrically-disubstituted imidazole-4,5-dicarboxamides with intramolecularly hydrogen bonded conformations that predispose th...

Compound libraries are important requirement in target-based drug discovery. In the present work, a small focused compound library based on β-aminoketone scaffold has been prepared combining microwave-assisted organic synthesis (MAOS) with polymer-as...

Visualization of the chemical space is useful in many aspects of chemistry, including compound library design, diversity analysis, and exploring structure–property relationships, to name a few. Examples of notable research areas where the visua...

Pyrimidine is a privileged scaffold in many synthetic compounds exhibiting diverse pharmacological activities, and is used for therapeutic applications in a broad spectrum of human diseases. In this study, we prepared a small set of pyrimidine librar...

The “Critical Assessment of Small Molecule Identification” (CASMI) contest was aimed in testing strategies for small molecule identification that are currently available in the experimental and computational mass spectrometry community. We have appli...

American Foulbrood, caused by Paenibacillus larvae, is the most devastating bacterial honey bee brood disease. Finding a treatment against American Foulbrood would be a huge breakthrough in the battle against the disease. Recently, small molecule inh...

The synthesis of combinatorial compound libraries has become a powerful lead finding tool in modern drug discovery. The ability to synthesize rapidly, in high yield, new chemical entities with low molecular weight on a solid support has a recognized...

The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2...

The synthesis of saccharin (1,2-benzisothiazol-3-one-1,1-dioxide) derivatives substituted on the benzene ring has seen limited development despite the longevity of this compound’s use as an artificial sweetener. This type of saccharin derivative woul...

Because of the importance of the HNK-1 carbohydrate for preferential motor reinnervation after injury of the femoral nerve in mammals, we screened NIH Clinical Collection 1 and 2 Libraries and a Natural Product library comprising small organic compou...

Insomnia is an important public health problem. The currently available treatments for insomnia can cause some adverse effects. Orexin receptors 1 (OX₁R) and 2 (OX₂R) are burgeoning targets for insomnia treatment. It is an effective approach to scree...

A small library of 6-aminoquinoxalines has been prepared by nucleophilic substitution of 6-fluoroquinoxaline with amines and nitrogen-containing heterocycles under computer-controlled microwave irradiation. Some compounds were found to be potent inhi...

Background/Objectives: Zika fever is a disease caused by the Zika virus (ZIKV). Symptomatic cases may be associated with neurological disorders in adults, as well as congenital Zika syndrome and other birth defects during pregnancy. In 2016, Zika fev...

The synthesis of a small library of dihydrouracils spiro-fused to pyrrolidines is described. These compounds are synthesized from b-aryl pyrrolidines, providing products with the 2-arylethyl amine moiety, a structural feature often encountered in com...

In the present study, we established a practical and cost-effective high throughput screening assay, which relies on the measurement of the motility of Caenorhabditis elegans by infrared light-interference. Using this assay, we screened 14,400 small...

High-throughput virtual screening (HTVS) is, in conjunction with rapid advances in computer hardware, becoming a staple in drug design research campaigns and cheminformatics. In this context, virtual compound library design becomes crucial as it gene...

Protein-protein interactions (PPIs) are associated with various diseases; hence, they are important targets in drug discovery. However, the physicochemical empirical properties of PPI-targeted drugs are distinct from those of conventional small molec...

The screening of chemical libraries based on cellular biosensors is a useful approach to identify new hits for novel therapeutic targets involved in rare genetic pathologies, such as β-thalassemia and sickle cell disease. In particular, pharmaco...

Fragment-based drug discovery (FBDD) focuses on small compounds, known as fragments, typically with a molecular weight of less than 300 Da. This study highlights the benefits of employing a pure natural product library for FBDD, contrasting with the...

On an annual basis the flagellate protozoan, Giardia duodenalis, is responsible for an estimated one billion human infections of which approximately two hundred million cause disease. However, the treatment of Giardia infections is reliant on a small...

The emergence of bacteria that co-express serine- and metallo- carbapenemases is a threat to the efficacy of the available β-lactam antibiotic armamentarium. The 4-amino-1,2,4-triazole-3-thione scaffold has been selected as the starting chemical...

Given the known biological activity of both natural and synthetic substituted 1H-phenalen-1-ones, the generation of a small chemically and structurally diverse 1H-phenalen-1-one-based library of compounds was warranted. Herein, we have synthesized se...

In drug discovery, reliable and fast dereplication of known compounds is essential for identification of novel bioactive compounds. Here, we show an integrated approach using ultra-high performance liquid chromatography-diode array detection-quadr...

A small library of 23 pyrrole-based tricyclic derivatives bearing bulky amine moieties was synthesized, and all were evaluated for their antiviral activities against ZIKV and SARS-CoV. Three compounds, derivatives 2g, 2h and 2j, elicited interesting...

This study aimed to identify potential BCL-2 small molecule inhibitors using deep neural networks (DNN) and random forest (RF), algorithms as well as molecular docking and molecular dynamics (MD) simulations to screen a library of small molecules. Th...

Inspired by the many reported successful applications of DNA-encoded chemical libraries in drug discovery projects with protein targets, we decided to apply this platform to nucleic acid targets. We used a 120-billion-compound set of 33 distinct DNA-...

A solvent-free synthesis of 1,4-disubstituted-1,2,3-triazoles using neat azides and alkynes and a copper(I) polymer supported catalyst (Amberlyst^® A21•CuI) is presented herein. As it provides the products in high yields and purities within minutes, t...

West Nile virus (WNV) is a positive sense, single-stranded RNA virus that can cause illness in humans when transmitted via mosquito vectors. Unfortunately, no antivirals or vaccines are currently available, and therefore efficient and safe antivirals...

Bornyl caffeate (1) was previously isolated by us from Valeriana (V.) wallichii rhizomes and identified as an anti-leishmanial substance. Here, we screened a small compound library of synthesized derivatives 1–30 for activity against schistosomula of...

In our initial publication on the in vitro testing of more than 200 compounds, we demonstrated that small molecules can inhibit phagocytosis. We therefore theorized that a small molecule drug discovery-based approach to the treatment of immune cytope...

A data set of 48 propafenone-type modulators of multidrug resistance was used to investigate the influence of learning rate and momentum factor on the predictive power of artificial neural networks of different architecture. Generally, small learning...

The synthesis of aldehyde-PAP as a key precursor through a triple reaction sequence: diazotization-addition/CuAAC/oxidation by using 4-methyl-N³-[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine as the starting material is described. Furthermore, a...

The development of new bioactive compounds represents one of the main purposes of the drug discovery process. Various tools can be employed to identify new drug candidates against pharmacologically relevant biological targets, and the search for new...

The screening of a small library of Japanese herbal tea extracts revealed significant anti-glycation activity in the leaves of Angelica keiskei. LC-MS analysis led to the identification of twenty compounds in this herb tea, including seven flavonoids...