Search results for "chemical science"
showing 10 items of 9771 documents
Quinoline anticancer agents active on DNA and DNA-interacting proteins: From classical to emerging therapeutic targets.
2021
Quinoline is one of the most important and versatile nitrogen heterocycles embodied in several biologically active molecules. Within the numerous quinolines developed as antiproliferative agents, this review is focused on compounds interfering with DNA structure or with proteins/enzymes involved in the regulation of double helix functional processes. In this light, a special focus is given to the quinoline compounds, acting with classical/well-known mechanisms of action (DNA intercalators or Topoisomerase inhibitors). In particular, the quinoline drugs amsacrine and camptothecin (CPT) have been studied as key lead compounds for the development of new agents with improved PK and tolerability…
Modular Solid-Phase Synthesis of Antiprotozoal Barnesin Derivatives
2020
Here, we applied and optimized a solid support (SP)-based Horner-Wadsworth-Emmons reagent to prepare SP-bound vinylogous amino acids. Subsequent SP-based peptide synthesis, global deprotection, and chemical modifications yielded 14 lipodipeptides carrying vinylogous amino acids, including the natural product barnesin A (1). Biological evaluation revealed that several synthesized derivatives show micromolar to nanomolar inhibitory activity against papain-like cysteine proteases, human cathepsin L, and rhodesain.
An overview of organosulfur compounds from Allium spp.: From processing and preservation to evaluation of their bioavailability, antimicrobial, and a…
2019
The use of Allium species and their extracts has been known since immemorial times due to their health beneficial properties. It is known that functional properties of Allium genus come from the high content of bioactive compounds. The biological activity of Allium extracts will be conditioned by the type of Allium variety, agricultural conditions, and specific extraction process used since all these factors affect the content and the profile of bioactive compounds. Innovative extraction techniques in comparison to conventional processes could be considered as a promising tool to recover bioactive compounds from Allium spp. with antimicrobial and anti-inflammatory properties. Trying to fill…
Squaric Acid-Based Radiopharmaceuticals for Tumor Imaging and Therapy.
2021
Targeting vectors bound to a chelator represent a significant fraction of radiopharmaceuticals used nowadays for diagnostic and therapeutic purposes in nuclear medicine. The use of squaramides as coupling units for chelator and targeting vector helps to circumvent the disadvantages of several common coupling methods. This review gives an overview of the use of squaric acid diesters (SADE) as linking agents. It focuses on the conjugation of cyclic chelators, e.g., DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), as well as hybrid chelators like AAZTA5 (6-pentanoic acid-6-amino-1,4-diazepine tetracetic acid) or DATA5m (6-pentanoic acid-6-amino-1,4-diazapine-triacetate) to diff…
Synthesis and biological evaluation of sphingosine kinase 2 inhibitors with anti-inflammatory activity.
2019
The synthesis of inhibitors of SphK2 with novel structural scaffolds is reported. These compounds were designed from a molecular modeling study, in which the molecular interactions stabilizing the different complexes were taken into account. Particularly interesting is that 7‐bromo‐2‐(2‐phenylethyl)‐2,3,4,5‐tetrahydro‐1,4‐epoxynaphtho[1,2‐b]azepine, which is a selective inhibitor of SphK2, does not exert any cytotoxic effects and has a potent anti‐inflammatory effect. It was found to inhibit mononuclear cell adhesion to the dysfunctional endothelium with minimal impact on neutrophil–endothelial cell interactions. The information obtained from our theoretical and experimental study can be us…
Rationally designed haptens for highly sensitive monoclonal antibody-based immunoanalysis of fenhexamid.
2018
Immunochemical methods have been consolidated during the last few years as complementary analytical strategies for chemical contaminant and residue determination. However, generation of suitable immunoreagents for small organic molecules demands adequate hapten design. In this study, fenhexamid was considered as a model compound and novel haptens were designed and synthesized in order to evaluate the influence of the linker tethering site on antibody binding properties and immunoassay parameters. Haptens were conceived with the spacer arm at different positions, while the more antigenic aromatic moiety was kept free. The synthesis of these functionalized compounds was accomplished by total …
Macrolides May Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Entry into Cells: A Quantitative Structure Activity Relationship Study and Exp…
2021
The global pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening the health and economic systems worldwide. Despite the enormous efforts of scientists and clinicians around the world, there is still no drug or vaccine available worldwide for the treatment and prevention of the infection. A rapid strategy for the identification of new treatments is based on repurposing existing clinically approved drugs that show antiviral activity against SARS-CoV-2 infection. In this study, after developing a quantitative structure activity relationship analysis based on molecular topology, several macrolide antibiotics are identified as promising SARS-…
Non-covalent interactions of N-phenyl-1,5-dimethyl-1H-imidazole-4-carboxamide 3-oxide derivatives—a case of intramolecular N-oxide hydrogen bonds
2017
The crystal structures of new N-phenyl-1,5-dimethyl-1H-imidazole-4-carboxamide 3-oxide derivatives are reported. The results of X-ray diffraction showed the existence of intramolecular hydrogen bonding between carboxamide nitrogen donors and N-oxide oxygen acceptors. The use of Quantum Theory of Atoms in Molecules allowed its classification as a strong interaction, with energy about 10 kcal/mol, and of intermediate character between closed shell and shared bonds. Comparison of experimental data and quantum theoretical calculations indicated that a substituent attached to the phenyl ring in the para position influences the strength and geometry of the title hydrogen bonding. Stronger π-elect…
Structure, Biosynthesis, and Bioactivity of Photoditritide from Photorhabdus temperata Meg1
2019
A new cyclic peptide photoditritide (1), containing two rare amino acid d-homoarginine residues, was isolated from Photorhabdus temperata Meg1 after the nonribosomal peptide synthetase encoding gene pdtS was activated via promoter exchange. The structure of 1 was elucidated by HR-MS and NMR experiments. The absolute configurations of amino acids were determined according to the advanced Marfey's method after hydrolysis of 1. Bioactivity testing of 1 revealed potent antimicrobial activity against Micrococcus luteus with an MIC value of 3.0 μM and weak antiprotozoal activity against Trypanosoma brucei rhodesiense with an IC50 value of 13 μM. Additionally, the biosynthetic pathway of 1 was als…
Targeting a Targeted Drug: An Approach Toward Hypoxia-Activatable Tyrosine Kinase Inhibitor Prodrugs
2016
Tyrosine kinase inhibitors (TKIs), which have revolutionized cancer therapy over the past 15 years, are limited in their clinical application due to serious side effects. Therefore, we converted two approved TKIs (sunitinib and erlotinib) into 2-nitroimidazole-based hypoxia-activatable prodrugs. Kinetics studies showed very different stabilities over 24 h; however, fast reductive activation via E. coli nitroreductase could be confirmed for both panels. The anticancer activity and signaling inhibition of the compounds against various human cancer cell lines were evaluated in cell culture. These data, together with molecular docking simulations, revealed distinct differences in the impact of …