Design of Conjugates Based on Sesquiterpene Lactones with Polyalkoxybenzenes by “Click” Chemistry to Create Potential Anticancer Agents

Abstract

Using the methodology of “click” chemistry, a singular method has been developed for the synthesis of unique conjugates based on sesquiterpene lactones: dehydrocostuslactone and alantolactone with polyalkoxybenzenes. To expand the structural range of the resulting conjugates, the length of the 1,2,3-triazole spacer was varied. For all synthesized compounds, the cytotoxic profile was determined on the cell lines of tumor origin (SH-SY5Y, HeLa, Hep-2, A549) and normal Hek 293 cells. It was found that the compounds based on alantolactone 7a–d with a long spacer and substances containing dehydrocostuslactone 10a–d with a short spacer have the greatest toxic effect. The decrease in cell survival under the action of these conjugates may be due to their ability to cause dissipation of the transmembrane potential of mitochondria and inhibit the process of glycolysis, leading to cell death. The obtained results confirm the assumption that the development of conjugates based on sesquiterpene lactones and polyalkoxybenzenes can be considered as a promising strategy for the search for potential antitumor agents.

Design, synthesis and antiviral evaluation of novel conjugates of the 1,7,7‐trimethylbicyclo[2.2.1]heptane scaffold and saturated N‐heterocycles via 1,2,3‐triazole linker

“…We used similar conditions earlier for designing hybrid biologically active compounds based on natural substrates. [ 15,16 ]…”

“…We used similar conditions earlier for designing hybrid biologically active compounds based on natural substrates. [15,16] The influence of the carbon-oxygen bond arrangement in the initial alkyne (±)-1 on the antiviral properties of the final products was investigated by introducing a triple bond into the structure of (-)borneol. The structure of compound (±)-1 has an ether group in the exo-position, while the hydroxyl group in the structure of (-)-borneol is in the endo-position, enabling an analogue of compound (±)-1 to be synthesised with a different arrangement of the carbon-oxygen bond.…”

Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases

“…Among natural compounds, sesquiterpene lactones also play an important role in the development of therapeutic agents due to their wide range of biological activities and promising pharmacological profiles [213][214][215][216][217][218]. One of the outstanding discoveries of traditional Chinese medicine is artemisinin, which exhibits excellent anti-malarial activity and is isolated from Artemisia annua L. [219,220].…”

An indole diketopiperazine alkaloid and a bisabolane sesquiterpenoid with unprecedented skeletons from Aspergillus fumigatus

“…17 Due to their fascinating structures and biological activities, indole diketopiperazines and sesquiterpenoids have attracted increasing attention from the biosynthetic, organic synthetic, and phytochemical communities. 6,7,[21][22][23] The fungus Aspergillus fumigatus is a rich source of indole diketopiperazines, notably neoechinulin A (R1), which exhibited a potent inhibitory effect against SARS-CoV-2 M pro with an IC 50 value of 0.47 μM, which is comparable to the reference standard GC376. 24 In addition to indole diketopiperazine, spirolactam alkaloids [pseurotin A (R6) had inhibitory effect on glioma cells with an IC 50 value of 0.51 μM], fumiquinazolines [fumiquinazoline A (R7) possessed antifeedant activity with antifeedant index of 45.0%], tryptoquivalines [tryptoquivaline J (R8) inhibited the proliferation of breast cancer cells], terpenoids [ pyripyropene A (R11) displayed inhibition of cholesterol acyltransferase with an IC 50 value of 0.058 μM], and polyketones [sulfurasperine D (R14) exhibited antioxidant activity with an IC 50 value of 1.65 μM] are also their metabolites, as shown in Fig.…”

“…17 Due to their fascinating structures and biological activities, indole diketopiperazines and sesquiterpenoids have attracted increasing attention from the biosynthetic, organic synthetic, and phytochemical communities. 6,7,21–23…”