Dizajn, sinteza i antiproliferativna aktivnost novih cikloalkanspiro-5-hidantoinskih derivata: Veza između strukture i aktivnosti

Abstract

Spirohidantoini pripadaju grupi jedinjenja koja ispoljavaju širok spektar biološke aktivnosti. Do sada su derivati spirohidantoina identifikovani kao antikonvulzivi, antiaritmici, antidijabetici i antitumorni agensi. U cilju ispitivanja biološke aktivnosti, testirana je citotoksičnost novih serija jedinjenja: 3-(4-supstituisanih benzil)-1,3-diazaspiro[4.5]dekan-2,4-diona, 3-(2-(4-supstituisanih fenil)-2-oksoetil)-1,3-diazaspiro-[4.5]-dekan-2,4-diona, 3-(4-supstituisanih benzil)-1,3-diazaspiro[4.6]undekan-2,4-diona i 3-(2-(4-supstituisanih fenil)-2-oksoetil)-1,3-diazaspiro[4.6]undekan- -2,4-diona. Citotoksična aktivnost određena je MTT testom prema ćelijskim linijama humane mijeloidne leukemije (K562), raka debelog creva (HCT-116) i raka dojke (MDA-MB-231). Testirana jedinjenja pokazala su značajnu citotoksičnost prema svim ćelijskim linijama, a naročito su se istakli derivati koji u okviru svoje strukture sadrže halogene kao supstituente. Uticaj sternih i elektronskih svojstava supstituenata na aktivnost proučavanih jedinjenja, analiziran je primenom QSAR modela.

Spiroydantoins belong to a group of compounds exhibiting a wide range of biological activities. Until now, the spirohydantoin derivatives are identified as anticonvulsants, antiarrhythmic drugs, antidiabetic agents and antitumor agents. In order to investigate the biological activity was tested on the cytotoxicity of the new series of compounds: 3-(4-substituted benzyl)-1,3-diazaspiro[4.5]decane-2,4-dione, 3-(2-(4-substituted phenyl)-2-oxoethyl)-1,3-diazaspiro[4.5]decane2,4-dione, 3-(4-substituted benzyl)-1,3--diazaspiro-[4.6]undecane-2,4-dione and 3-(2-(4-substituted phenyl)-2-oxoethyl)-1,3-diazaspiro[4.6]-undecane-2,4-dione. Cytotoxic activity was assessed by MTT assay cell lines of human myeloid leukemia (K562), colon (HCT-116) and breast cancer cells (MDA-MB-231). The test compounds showed a significant cytotoxicity to all cell lines, and in particular the derivatives containig within its structure halogens as substituents. The effect of steric and electronic properties of the substituents on activity of studed compounds, was analyzed by QSAR models.