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. Extrinsic factors such as microtubule-targeting agents (MTAs) can also affect MT dynamics. MTAs can be divided into two main categories: microtubule-stabilizing agents (MSAs) and microtubule-destabilizing agents (MDAs). Thus, the MT skeleton is an important target for anticancer therapy. This review discusses factors that determine the microtubule dynamics in normal and cancer cells and describes microtubule–MTA interactions, highlighting the importance of tubulin isoform diversity and post-translational modifications in MTA responses and the consequences of such a phenomenon, including drug resistance development.

A tandem enzyme‐catalyzed Knoevenagel reaction with acetaldehyde is presented. A new protocol for the synthesis of the desired products through a tandem process based on the enzymatic hydrolysis and Knoevenagel reaction starting from acetaldehyde precursors is disclosed. The influence of the reaction conditions including organic solvent, enzyme type, and temperature on the reaction course was tested. Further, this protocol was extended by subsequent tandem chemoenzymatic transformations leading to epoxides.

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. We have also demonstrated that vinyl esters of cyclic carboxylic acids can be successfully applied for domino ring-opening ring-closing metathesis sequences.

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. These advantages make umbelliferyl carbonates highly suitable substrates for high-throughput screening. Moreover, we report the use of chiral fluorogenic carbonates as enantiopreference probes.

The synthesis of photoswitchable azo-dibenzo[b,f]oxepine derivatives and microtubule inhibitors were described. Subsequently, we examined the reaction of methoxy derivative 3-nitrodibenzo[b,f]oxepine with different aldehydes and in the presence of BF3·OEt2 as a catalyst. Our study provided a very concise method for the construction of the azo-dibenzo[b,f]oxepine skeleton. The analysis of products was run using experimental and theoretical methods. Next, we evaluated the E/Z isomerization of azo-dibenzo[b,f]oxepine derivatives, which could be photochemically controlled using visible-wavelength light.

No abstract

No abstract

Dibenzo[b, f]oxepine derivatives are an important scaffold in natural, medicinal chemistry, and these derivatives occur in several medicinally relevant plants. Two dibenzo[b, f]oxepines were selected and connected with appropriate fluorine azobenzenes. In the next step, the geometry of E/Z isomers was analyzed using density functional theory (DFT) calculations. Then the energies of the HOMO and LUMO orbitals were calculated for the E/Z isomers to determine the HOMO-LUMO gap. Next, modeling of the interaction between the obtained isomers of the compounds and the colchicine α and β-tubulin binding site was performed. The investigated isomers interact with the colchicine binding site in tubulin with a part of the dibenzo[b, f]oxepine or in a part of the azo switch, or both at the same time. Based on the UV-VIS spectra, it was found that in the case of compounds with an azo bond in the meta position, the absorption bands n→π* for both geometric isomers and their separation from π→π* are visible. These derivatives therefore have the potential to be used in photopharmacology.