Prirodni stiril-laktoni, njihovi derivati i analozi kao potencijalni antitumorski agensi: Dizajn, sinteza i SAR ispitivanja

Abstract

U radu je ostvarena sinteza četiri prirodna proizvoda, goniobutenolida A i B, krasalaktona D i 3-deoksi-kardiobutanolida i 32 derivata i analoga polazeći iz D-glukoze. Sinteza prirodnog stiril-laktona, kardiobutanolida i njegova 4 derivata je izvedena polazeći iz D-ksiloze. Ispitan je uticaj sintetizovanih jedinjenja na inhibiciju rasta 10 tumorskih i jedne zdrave ćelijske linije. Uspostavljene su i korelacije izmedju strukture i antiproliferativne aktivnosti (SAR) i ispitan je mehanzam antitumorskog dejstva.

Synthesis of four natural products: goniobutenolide A and B, crassalactone D, 3-deoxy-cardiobutanolide and their 32 analogues and derivatives is accomplished starting from D-glucose. Synthesis of natural styryl lactone cardiobutanolide and its four derivatives is achieved starting from D-xylose. Synthesized natural lactones, their analogues and derivatives were evaluated for their antiproliferative activity against ten malignant cell lines as well as against a single normal cell line. Influence of functional groups on antitumour activity was established by correlating structures of synthesized compounds with their biological activity (SAR). Also, mechanism of antitumour action was investigated.