An original Method for the Synthesis and the Study of Its Biological Activity of Natural Lembehyne B Aromatic Analogs

: In the development of earlier initiated studies on the synthesis of natural and synthetic neuritogenic alkynols, lembehynes A – C, which, simultaneously, exhibit high antitumor activity, we have developed a method for the synthesis of an analogue of natural lembehyne B containing a phenyl radical in its structure. It has been shown that the synthesized aromatic analogue of lembehyne B exhibits higher antitumor activity in vitro to a number of tumor cell lines (Jurkat, K562 and U937).

Earlier, we reported on the complete synthesis of natural lembehyne B, as well as the preparation of synthetic derivatives of lembehyne B, containing a 1,3-diyne fragment in their structure. The synthesized lembehynes showed cytotoxicity towards tumor cells of the Jurkat, U937, K562, HeLa and Hek293 lines. and neuritogenic activity on Neuro 2A mouse neuroblastoma cells [11,12].
It is known that π-π-stacking interaction of aromatic radicals, biologically active compounds, with nitrogenous bases of DNA or RNA of tumor cells, can lead to disruption of the processes of transcription and replication, leading to apoptosis [13,14].

Scheme 1. Synthesis of aromatic derivatives of lembehyne B.
For the synthesized compounds, the in vitro antitumor activity was assessed on Jurkat, K562, HL-60, U937 cell lines and fibroblasts, including the determination of IC50 using flow cytometry and multiplex analysis.

Conclusions
An effective method was developed for the preparation of aromatic derivatives of lembehyne B, using at the key stage of synthesis the reaction of catalytic cross-cyclomagnesiation of terminal 1,2-dienes (Dzhemilev reaction), and their antitumor activity was also studied using modern methods of flow cytometry and multiplex analysis.

Conflicts of Interest:
The authors declare no conflict of interest.