Synthesis of New Functionally Substituted Bicyclo[4.2.1]nona-2,4,7-trienes by Co(I)-Catalyzed [6π + 2π] Cycloaddition of 1-Benzoylcycloheptatriene

Functionally substituted bicyclo[4.2.1]nona-2,4,7-trienes were synthesized for the first time on the basis of the reaction of [6π + 2π] cycloaddition of hexyn-1 and 4-pentynenitrile to 1-benzoylcycloheptatriene under the action of the three-component catalytic system Co(acac)2(dppe)/Zn/ZnI2

Co(I)-Catalyzed [4π + 2π] Cycloaddition of 1,2-Dienes to 1,3,5-Cyclooctatriene in the Synthesis of Previously Undescribed Tricyclo[4.2.2.02,5]Decenes

The catalytic [4π + 2π]-cycloaddition of monosubstituted and disubstituted 1,2-dienes to 1,3,5-cyclooctatriene under the action of Co(acac)2(dppe)/Zn/ZnI2 was performed for the first time to produce substituted tricyclo[4.2.2.02,5]dec-7-enes

Synthesis of 1,3-Diyne Derivatives of Lembehyne B with Antitumor and Neuritogenic Activity

The report presents data from our studies on obtaining lembehyne B derivatives with cytotoxic and neuritogenic activity. The methods and approaches to the synthesis of the above-mentioned lembehynes presented in the report are based on the use of the catalytic cross-cyclomagnesiation of 1,2-dienes (the Dzhemilev reaction) at the key stage of the synthesis

Synthesis of 1,3-Diyne Derivatives of Lembehyne B with Antitumor and Neuritogenic Activity

The report presents data from our studies on obtaining lembehyne B derivatives with cytotoxic and neuritogenic activity. The methods and approaches to the synthesis of the above-mentioned lembehynes presented in the report are based on the use of the catalytic cross-cyclomagnesiation of 1,2-dienes (the Dzhemilev reaction) at the key stage of the synthesis

Development of New Effective Methods for the Synthesis of Lembehynes A–C Exhibiting Cytotoxic and Neuritogenic Activity

This report presents data on our studies on the preparation of the precursor lembehyne A and the complete stereoselective synthesis of natural lembehynes B and C, which have cytotoxic and neuritogenic activity. All methods and approaches to the synthesis of the above-mentioned lembehynes presented in this report are based on the use of the catalytic cross-cyclomagnesiation of 1,2-dienes (Dzhemilev reaction) at the key stage of the synthesis

Natural Acetogenins, Chatenaytrienins-1, -2, -3 and -4, Mitochondrial Potential Uncouplers and Autophagy Inducers—Promising Anticancer Agents

The present paper details the complete stereoselective synthesis of four natural acetogenins, chatenaytrienins-1, -2, -3 and -4, previously isolated from the roots of fruit trees of the family Annonaceae (A. nutans and A. muricata), as an inseparable mixture. The novel organometallic reactions, developed by the authors, of Ti-catalyzed cross-cyclomagnesiation of O-containing and aliphatic allenes using available Grignard reagents were applied at the key stage of synthesis. We have studied the biological activity of the synthesized individual chatenaytrienins-1, -2, -3 and -4 in vitro, including their cytotoxicity in a panel of tumor lines and their ability to induce apoptosis, affect the cell cycle and mitochondria, and activate the main apoptotic signaling pathways in the cell, applying modern approaches of flow cytometry and multiplex analysis with Luminex xMAP technology. It has been shown that chatenaytrienins affect mitochondria by uncoupling the processes of mitochondrial respiration, causing the accumulation of ROS ions, followed by the initiation of apoptosis. The most likely mechanism for the death of cortical neurons from the consumption of tea from the seeds of Annona fruit is long-term chronic hypoxia, which leads to the development of an atypical form of Parkinson’s disease that is characteristic of the indigenous inhabitants of Guam and New Caledonia

Pentacyclic Triterpenoids-Based Ionic Compounds: Synthesis, Study of Structure–Antitumor Activity Relationship, Effects on Mitochondria and Activation of Signaling Pathways of Proliferation, Genome Reparation and Early Apoptosis

The present research paper details the synthesis of novel ionic compounds based on triterpene acids (betulinic, oleanolic and ursolic), with these acids acting both as anions and connected through a spacer with various nitrogen-containing compounds (pyridine, piperidine, morpholine, pyrrolidine, triethylamine and dimethylethanolamine) and acting as a cation. Based on the latter, a large number of ionic compounds with various counterions (BF4-, SbF6-, PF6-, CH3COO-, C6H5SO3-, m-C6H4(OH)COO- and CH3CH(OH)COO-) have been synthesized. We studied the cytotoxicity of the synthesized compounds on the example of various tumor (Jurkat, K562, U937, HL60, A2780) and conditionally normal (HEK293) cell lines. IC50 was determined, and the influence of the structure and nature of the anion and cation on the antitumor activity was specified. Intracellular signaling, apoptosis induction and effects of the most active ionic compounds on the cell cycle and mitochondria have been discussed by applying modern methods of multiparametric enzyme immunoassay and flow cytometry

Development of New Effective Methods for the Synthesis of Lembehynes A–C Exhibiting Cytotoxic and Neuritogenic Activity

This report presents data on our studies on the preparation of the precursor lembehyne A and the complete stereoselective synthesis of natural lembehynes B and C, which have cytotoxic and neuritogenic activity. All methods and approaches to the synthesis of the above-mentioned lembehynes presented in this report are based on the use of the catalytic cross-cyclomagnesiation of 1,2-dienes (Dzhemilev reaction) at the key stage of the synthesis

An Original Method for the Synthesis of Partially Deuterated Natural Lembehyne B and the Study of Its Biological Activity

An efficient method for the synthesis of a partially deuterated analogue of the natural neuritogenic alkynol, lembehyne B, has been developed for the first time, based on the use of a new reaction of Ti-catalyzed cross-cyclomagnesiation of O-containing 1,2-dienes and terminal aliphatic 1,2-dienes using EtMgBr in high yield. The introduction of two deuterium atoms is carried out at the stage of treatment of the formed in situ magnesacyclopentane with D2O

Synthesis and Anticancer Activity of Hybrid Molecules Based on Lithocholic and (5<i>Z</i>,9<i>Z</i>)-Tetradeca-5,9-dienedioic Acids Linked via Mono(di,tri,tetra)ethylene Glycol and α,ω-Diaminoalkane Units

For the first time, hybrid molecules were synthesized on the basis of lithocholic and (5Z,9Z)-1,14-tetradeca-5,9-dienedicarboxylic acids, obtained in two stages using the homo-cyclomagnesiation reaction of 2-(hepta-5,6-diene-1-yloxy)tetrahydro-2H-pyran at the key stage. The resulting hybrid molecules containing 5Z,9Z-dienoic acids are of interest as novel synthetic biologically active precursors to create modern drugs for the treatment of human oncological diseases. The synthesized hybrid molecules were found to exhibit extremely high in vitro inhibitory activity against human topoisomerase I, which is 2–4 times higher than that of camptothecin, a known topoisomerase I inhibitor. Using flow cytometry and fluorescence microscopy, it was first shown that these new molecules are efficient apoptosis inducers in HeLa, U937, Jurkat, K562, and Hek293 cell cultures. In addition, the results of investigations into the effect of the synthesized acids on mitochondria and studies of possible DNA damage in Jurkat tumor cells are also presented