Synthesis and Study of Building Blocks with Dibenzo[]oxepine: Potential Microtubule Inhibitors.

The synthesis of biphenylmethoxydibenzo[]oxepine or photoswitchable fluorinated dibenzo[]oxepine derivatives with one or three azo bonds, potential microtubule inhibitors, is described. Our studies provide a concise method for constructing derivatives containing the dibenzo[]oxepine skeleton. An analysis of products was run using experimental and theoretical methods.

Development of 5-fluorouracil-dichloroacetate mutual prodrugs as anticancer agents.

5-Fluorouracil (5-FU) is one of the most widely applied chemotherapeutic agents with a broad spectrum of activity. However, despite this versatile activity, its use poses many limitations. Herein, novel derivatives of 5-FU and dichloroacetic acid have been designed and synthesized as a new type of codrugs, also known as mutual prodrugs, to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency.

First-in-Class Colchicine-Based Visible Light Photoswitchable Microtubule Dynamics Disrupting Agent.

Compounds that disrupt microtubule dynamics, such as colchicine, paclitaxel, or Vinca alkaloids, have been broadly used in biological studies and have found application in clinical anticancer medications. However, their main disadvantage is the lack of specificity towards cancerous cells, leading to severe side effects. In this paper, we report the first synthesis of 12 new visible light photoswitchable colchicine-based microtubule inhibitors .

Systematic Studies on Anti-Cancer Evaluation of Stilbene and Dibenzo[]oxepine Derivatives.

Cancer is one of the most common causes of human death worldwide; thus, numerous therapies, including chemotherapy, have been and are being continuously developed. In cancer cells, an aberrant mitotic spindle-a microtubule-based structure necessary for the equal splitting of genetic material between daughter cells-leads to genetic instability, one of the hallmarks of cancer. Thus, the building block of microtubules, tubulin, which is a heterodimer formed from α- and β-tubulin proteins, is a useful target in anti-cancer research.

Synthesis and Study of Dibenzo[]oxepine Combined with Fluoroazobenzenes-New Photoswitches for Application in Biological Systems.

Dibenzo[]oxepine derivatives are an important scaffold in natural, medicinal chemistry, and these derivatives occur in several medicinally relevant plants. Two dibenzo[]oxepines were selected and connected with appropriate fluorine azobenzenes. In the next step, the geometry of / isomers was analyzed using density functional theory (DFT) calculations.

Synthesis and Investigations of Building Blocks with Dibenzo[,] Oxepine for Use in Photopharmacology.

The synthesis of photoswitchable -dibenzo[,]oxepine derivatives and microtubule inhibitors were described. Subsequently, we examined the reaction of methoxy derivative 3-nitrodibenzo[,]oxepine with different aldehydes and in the presence of BF·OEt as a catalyst. Our study provided a very concise method for the construction of the -dibenzo[,]oxepine skeleton.

Development of novel derivatives of stilbene and macrocyclic compounds as potent of anti-microtubule factors.

Microtubules (composed of α- and β-tubulin heterodimers) ubiquitous cellular polymers are important components of the cytoskeleton and play diverse roles within the cell, such as maintenance of cell structure, protein trafficking or chromosomal segregation during cell division. The polymers of tubulin play a pivotal role in mitosis and are regarded as an excellent target for chemotherapeutic agents to treat cancer. This review presents a brief overview of the synthesis and mechanism of action of new compounds targeting the dynamic of microtubule - tubulin polymerization/depolymerization.

Intrinsic and Extrinsic Factors Affecting Microtubule Dynamics in Normal and Cancer Cells.

Microtubules (MTs), highly dynamic structures composed of α- and β-tubulin heterodimers, are involved in cell movement and intracellular traffic and are essential for cell division. Within the cell, MTs are not uniform as they can be composed of different tubulin isotypes that are post-translationally modified and interact with different microtubule-associated proteins (MAPs). These diverse intrinsic factors influence the dynamics of MTs.

The stilbene and dibenzo[b,f]oxepine derivatives as anticancer compounds.

In the present study, the synthesis and cytotoxic effect of six stilbenes and three oxepine derivatives against two cancerous - HeLa and U87, and two normal - EUFA30 and HEK293 cell lines has been reported. The results of cytotoxic assay and flow cytometry analysis revealed that compounds 9-nitrobenzo[b]naphtho[1,2-f]oxepine (4), (E)-3,3',4,4',5,5'-hexamethoxystilbene (6) and 4-hydroxy-2',4'-dinitrostilbene (8) were the most active and their interaction with tubulin (crystal structure from PDB) has been analyzed by computer molecular modeling. Molecular docking of these compounds on colchicine binding site of the tubulin indicates the interaction of (4), (6) and (8) with tubulin.

Studies on the Synthesis of Endocyclic Enol Lactones via a RCM of Selected Vinyl Esters.

The novel and efficient approach toward the synthesis of endocyclic enol lactones was devised based on ring-closing metathesis of unsaturated carboxylic acids vinyl esters. Systematic studies revealed that vinyl esters are suitable substrates for RCM reaction. The developed methodology offers an easy route for synthetically challenging target molecules with different functional groups and substitution.

Evaluation of Pseudoenantiomeric Mixed Carbonates as Efficient Fluorogenic Probes for Enantioselectivity Screening.

We report mixed carbonates as enzyme substrates and demonstrate their application as fluorogenic probes for lipase and esterase enantiopreference screening. By the application of pseudoenantiomers with distinct fluorescence behaviors, it is possible to evaluate the activity and enantiopreference of hydrolytic enzymes. In order to validate our method, enantioselectivities calculated from fluorometric measurements were compared with the results obtained from larger-scale kinetic resolution.

Mixed carbonates as useful substrates for a fluorogenic assay for lipases and esterases.

Mixed carbonates of 7-hydroxy-4-methylcoumarin were shown to be a new class of probe for fluorogenic assays. They are promising substrates for fingerprinting enzyme hydrolytic activity, and proved particularly useful because of the low level of nonspecific degradation and ease of synthesis. They are highly relevant for screening lipase and esterase libraries.