New 1,3-Diynoic Derivatives of Natural Lembehyne B: Stereoselective Synthesis, Anticancer, and Neuritogenic Activity

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Feb 11

PMID 32039334

Citations 1

Authors

Lilya U Dzhemileva

Alexey A Makarov

Evgeny N Andreev

Elina Kh Makarova

Milyausha M Yunusbaeva

Vladimir A Dyakonov

Usein M Dzhemilev

Affiliations

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Abstract

An original method has been developed for the synthesis of 1,3-dyine derivatives of natural lembehyne B in high yields (50-67%) and with high selectivity (>98%). The key stage of the synthesis is new Ti-catalyzed cross-cyclomagnesiation of oxygenated and aliphatic 1,2-dienes induced by Grignard reagents. For studying the effect of the structure on the antitumor and neuritogenic activities, a series of lembehyne B analogues with different distances between the terminal hydroxy group and the 1,3-diyne moiety was prepared and tested for neuritogenic activity on mouse neuroblastoma Neuro 2A cells and for cytotoxicity, induction of apoptosis, and effects on the cell cycle using Jurkat, U937, K562, HeLa, and Hek293 tumor cell lines.

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