Nove izostere i bioizostere prirodnih stiril-laktona: dizajn, sinteza i antiproliferativna aktivnost

Abstract

U radu su ostvarene višefazne sinteze većeg broja analoga prirodnih stiril-laktona (+)-goniofufurona i 7-epi-(+)-goniofufurona polazeći iz D-glukoze. Ispitana je in vitro citotoksičnost sintetizovanih analoga prema devet malignih i jednoj zdravoj ćelijskoj liniji. Uspostavljeni su korelacioni odnosi izmedju strukture i antiproliferati vne aktivnosti sintetizovanih proizvoda, pored toga uradjeni su i dodatni biološki testovi koji se odnose na dokazivanje mehanizma citotoksičnog dejstva pomenutih stiril-laktona i analoga.

Multistep synthesis of a number of natural styryl lactones goniofufurone and 7-epi-goniofufurone analogues was achieved starting f rom D-glucose. In vitro cytotoxicity of newly synthetized analogues against nine human tumour cell lines and against a single normal cell line was evaluated. Structure-activity relationships were established for both natural products and analogues. Some additional biological tests related to the cell mechanisms underlying the cytotoxicity of the mentioned styryl lactones and analogues, were also carried out.