18 research outputs found
Structural and Pharmacological Effects of Ring-Closing Metathesis in Peptides
Applications of ring-closing alkene metathesis (RCM) in acyclic α- and β-peptides and closely related systems are reviewed, with a special emphasis on the structural and pharmacological effects of cyclization by RCM
Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin
We present a short and efficient way of synthesizing two synthetically versatile 4-quinolone-3-carboxylate building blocks by cyclopropanation-ring expansion of 3-chloroindoles with α-halodiazoacetates as the key step. This novel transformation was applied towards the synthesis of the antibiotic drug norfloxacin
Enhancement of iodinin solubility by encapsulation into cyclodextrin nanoparticles
Phenazine is known to regroup planar nitrogen-containing heterocyclic compounds. It was used here to
enhance the bioavailability of the biologically important compound iodinin, which is near insoluble in
aqueous solutions. Its water solubility has led to the development of new formulations using diverse
amphiphilic a-cyclodextrins (CDs). With the per-[6-desoxy-6-(3-perfluorohexylpropanethio)-2,3-di-O-methyl]-
a-CD, we succeeded to get iodinin-loaded nanoformulations with good parameters such as a size of
97.9 nm, 62% encapsulation efficiency and efficient control release. The study presents an interesting alternative
to optimizing the water solubility of iodinin by chemical modifications of iodinin
New prodrugs and analogs of the phenazine 5,10-dioxide natural products iodinin and myxin promote selective cytotoxicity towards human acute myeloid leukemia cells
Novel chemotherapeutic strategies for acute myeloid leukemia (AML) treatment are called for. We have recently demonstrated that the phenazine 5,10-dioxide natural products iodinin (3) and myxin (4) exhibit potent and hypoxia-selective cell death on MOLM-13 human AML cells, and that the N-oxide functionalities are pivotal for the cytotoxic activity. Very few structure–activity relationship studies dedicated to phenazine 5,10-dioxides exist on mammalian cell lines and the present work describes our efforts regarding in vitro lead optimizations of the natural compounds iodinin (3) and myxin (4). Prodrug strategies reveal carbamate side chains to be the optimal phenol-attached group. Derivatives with no oxygen-based substituent (–OH or –OCH3) in the 6th position of the phenazine skeleton upheld potency if alkyl or carbamate side chains were attached to the phenol in position 1. 7,8-Dihalogenated- and 7,8-dimethylated analogs of 1-hydroxyphenazine 5,10-dioxide (21) displayed increased cytotoxic potency in MOLM-13 cells compared to all the other compounds studied. On the other hand, dihalogenated compounds displayed high toxicity towards the cardiomyoblast H9c2 cell line, while MOLM-13 selectivity of the 7,8-dimethylated analogs were less affected. Further, a parallel artificial membrane permeability assay (PAMPA) demonstrated the majority of the synthesized compounds to penetrate cell membranes efficiently, which corresponded to their cytotoxic potency. This work enhances the understanding of the structural characteristics essential for the activity of phenazine 5,10-dioxides, rendering them promising chemotherapeutic agents
New prodrugs and analogs of the phenazine 5,10-dioxide natural products iodinin and myxin promote selective cytotoxicity towards human acute myeloid leukemia cells
Novel chemotherapeutic strategies for acute myeloid leukemia (AML) treatment are called for. We have recently demonstrated that the phenazine 5,10-dioxide natural products iodinin (3) and myxin (4) exhibit potent and hypoxia-selective cell death on MOLM-13 human AML cells, and that the N-oxide functionalities are pivotal for the cytotoxic activity. Very few structure–activity relationship studies dedicated to phenazine 5,10-dioxides exist on mammalian cell lines and the present work describes our efforts regarding in vitro lead optimizations of the natural compounds iodinin (3) and myxin (4). Prodrug strategies reveal carbamate side chains to be the optimal phenol-attached group. Derivatives with no oxygen-based substituent (–OH or –OCH3) in the 6th position of the phenazine skeleton upheld potency if alkyl or carbamate side chains were attached to the phenol in position 1. 7,8-Dihalogenated- and 7,8-dimethylated analogs of 1-hydroxyphenazine 5,10-dioxide (21) displayed increased cytotoxic potency in MOLM-13 cells compared to all the other compounds studied. On the other hand, dihalogenated compounds displayed high toxicity towards the cardiomyoblast H9c2 cell line, while MOLM-13 selectivity of the 7,8-dimethylated analogs were less affected. Further, a parallel artificial membrane permeability assay (PAMPA) demonstrated the majority of the synthesized compounds to penetrate cell membranes efficiently, which corresponded to their cytotoxic potency. This work enhances the understanding of the structural characteristics essential for the activity of phenazine 5,10-dioxides, rendering them promising chemotherapeutic agents
Zinc-Chelating Compounds as Inhibitors of Human and Bacterial Zinc Metalloproteases
Inhibition of bacterial virulence is believed to be a new treatment option for bacterial
infections. In the present study, we tested dipicolylamine (DPA), tripicolylamine (TPA), tris pyridine
ethylene diamine (TPED), pyridine and thiophene derivatives as putative inhibitors of the bacterial
virulence factors thermolysin (TLN), pseudolysin (PLN) and aureolysin (ALN) and the human zinc
metalloproteases, matrix metalloprotease-9 (MMP-9) and matrix metalloprotease-14 (MMP-14). These
compounds have nitrogen or sulfur as putative donor atoms for zinc chelation. In general, the
compounds showed stronger inhibition of MMP-14 and PLN than of the other enzymes, with Ki
values in the lower µM range. Except for DPA, none of the compounds showed significantly stronger
inhibition of the virulence factors than of the human zinc metalloproteases. TPA and Zn230 were
the only compounds that inhibited all five zinc metalloproteinases with a Ki value in the lower µM
range. The thiophene compounds gave weak or no inhibition. Docking indicated that some of the
compounds coordinated zinc by one oxygen atom from a hydroxyl or carbonyl group, or by oxygen
atoms both from a hydroxyl group and a carbonyl group, and not by pyridine nitrogen as in DPA
and TPA
Automated Event Detection and Classification in Soccer: The Potential of Using Multiple Modalities
Detecting events in videos is a complex task, and many different approaches, aimed at a large variety of use-cases, have been proposed in the literature. Most approaches, however, are unimodal and only consider the visual information in the videos. This paper presents and evaluates different approaches based on neural networks where we combine visual features with audio features to detect (spot) and classify events in soccer videos. We employ model fusion to combine different modalities such as video and audio, and test these combinations against different state-of-the-art models on the SoccerNet dataset. The results show that a multimodal approach is beneficial. We also analyze how the tolerance for delays in classification and spotting time, and the tolerance for prediction accuracy, influence the results. Our experiments show that using multiple modalities improves event detection performance for certain types of events