Targeting pathogenic Acanthamoeba castellanii using DNA minor groove binding agents.

DNA minor groove binders exhibit a high degree of sequence specificity and have a variety of biological actions including antiviral, anticancer, antibacterial, and anti-protozoal properties. Since it is the location of non-covalent interactions, the minor groove of double helical B-DNA is gaining significant interest as therapeutic targets. For the purpose of this investigation, the synthesis of five novel DNA minor groove binding agents was accomplished and antiparasitic efficacies were determined against Acanthamoeba castellanii of the T4 genotype in vitro.

Transcriptomic analysis of MCF7 breast cancer cells treated with MGBs reveals a profound inhibition of estrogen receptor genes.

Breast cancer poses a significant health risk worldwide. However, the effectiveness of current chemotherapy is limited due to increasing drug resistance and side effects, making it crucial to develop new compounds with novel mechanism of action that can surpass these limitations. As a consequence of their reversible and targeted mechanism, DNA minor groove binders (MGBs) are considered as a relatively safer and more effective alternative.

Design and discovery of urease and Helicobacter pylori inhibitors based on benzofuran/benzothiophene-sulfonate and sulfamate scaffolds for the treatment of ureolytic bacterial infections.

A series of sulfonate and sulfamate derivatives bearing benzofuran or benzothiophene scaffold exhibited potent inhibitory effect on urease enzyme. Most of the derivatives exhibited significantly higher potency than thiourea, the standard inhibitor. Compound 1s was identified as the most potent urease inhibitor with an IC value of 0.

Synthesis and Biological Activity of Sulfamate-Adamantane Derivatives as Glucosinolate Sulfatase Inhibitors.

The glucosinolate-myrosinase system, exclusively found in the family, is a main defense strategy against insect resistance. The efficient detoxification activity of glucosinolate sulfatases (GSSs) has successfully supported the feeding of on cruciferous plants. With the activity of GSSs hampered in , the toxic isothiocyanates produced from glucosinolates severely impair larval growth and adult reproduction.

The latest perspectives of small molecules FMS kinase inhibitors.

FMS kinase is a type III tyrosine kinase receptor that plays a central role in the pathophysiology and management of several diseases, including a range of cancer types, inflammatory disorders, neurodegenerative disorders, and bone disorders among others. In this review, the pathophysiological pathways of FMS kinase in different diseases and the recent developments of its monoclonal antibodies and inhibitors during the last five years are discussed. The biological and biochemical features of these inhibitors, including binding interactions, structure-activity relationships (SAR), selectivity, and potencies are discussed.

Complexity-to-Diversity and Pseudo-Natural Product Strategies as Powerful Platforms for Deciphering Next-Generation Therapeutics.

Stereochemical and skeletal complexity are particularly important vis-à-vis the cross-talks between a small molecule and a complementary active site of a biological target. This intricate harmony is known to increase selectivity, reduce toxicity, and increase the success rate in clinical trials. Therefore, the development of novel strategies for establishing underrepresented chemical space that is rich in stereochemical and skeletal diversity is an important milestone in a drug discovery campaign.

Divergent Protocol for the Synthesis of Isoquinolino[1,2-]quinazolinone and Isoquinolino[2,1-]quinazolinone Derivatives.

The development of robust and step-economic strategies to access structurally diverse drug-like compound collections remains a challenge. A distinct structural option that constitutes the core scaffold of many biologically significant molecules is the quinazolinone ring system. Several members of this family of privileged substructures have gained attention due to their diverse biological activities.

Stereodivergent Desymmetrization of Phenols En Route to Modular Access to Densely Functionalized Quinazoline and Oxazine Scaffolds.

The de novo assembly of stereochemically and skeletally diverse scaffolds is a powerful tool for the discovery of novel chemotypes. Hence, the development of modular, step- and atom-economic synthetic methods to access stereochemically and skeletally diverse compound collection is particularly important. Herein, we show a metal-free, stereodivergent build/couple/pair strategy that allows access to a unique collection of benzo[5,6][1,4]oxazino[4,3-]quinazoline, quinolino[1,2-]quinazoline and benzo[]benzo [4,5]imidazo[1,2-][1,4]oxazine scaffolds with complete diastereocontrol and wide distribution of molecular architectures.

Blue Light-Driven [4+2]-Cycloaddition: Diastereoselective Synthesis of Chromeno[4,3-]quinoline and Chromeno[4,3-][1,8]naphthyridine Scaffolds.

A one-pot, metal-free, light-driven [4+2]-cycloaddition reaction is described by accessing a diverse collection of chromeno[4,3-]quinoline and chromeno[4,3-][1,8]naphthyridine scaffolds in a diastereoselective manner. This process delivered stereoisomers, which were challenging to produce by an inverse-demand Diels-Alder reaction. The tetracyclic products were provided in good yields, promoted by rose bengal and blue light in a single operation.

Molecular Receptors for Recognition and Sensing of Nucleotides.

Nucleotides are constituents of nucleic acids and they have a variety of functions in cellular metabolism. Synthetic receptors and sensors are required to reveal the role of nucleotides in living organisms and mechanisms of signal transduction events. In recent years, a large number of nucleotide-selective synthetic receptors have been devised, which utilize different molecular designs and sensing mechanisms.

Cation Molecular Exchanger Based on a Conformational Hinge.

A cation molecular exchanger has been developed that consists of the bipyridine and crown ether receptor subunits. It has been shown that binding of the zinc(II) cation to the bipyridine subunit induces the conformational switching of the crown ether subunits, which results in a release of the potassium cation. Two conformational states of the cation exchanger have been supported by the results from solution- and solid-state studies.

Finding a receptor design for selective recognition of perrhenate and pertechnetate: hydrogen vs. halogen bonding.

Receptors bearing hydrogen and halogen bond donors for recognition of perrhenate and pertechnetate were designed and studied. Acyclic hosts with N-H and C-H binding sites showed the best selectivity for TcO4- and ReO4- over spherical and more basic tetrahedral anions.

Synthesis of crinane utilizing an allylic sulfoxide for the construction of a hydroindole ring via vinylogous C-N bond formation.

The synthesis of crinane is disclosed via intramolecular C-N bond formation by the displacement of an allylic sulfoxonium salt. The allylic sulfide precursor was synthesized by a ring-closing metathesis reaction. The quaternary carbon stereocenter was created by alkylation of a benzylic cyanide.