| Abstract | Jedna od strategija prilagodbi ekstremnom okolišu koju su razvili morski organizmi je sinteza sekundarnih metabolita. Ti spojevi nisu neophodni za rast, razvoj i razmnožavanje organizma već imaju adaptivnu, obrambenu, signalnu ili neku drugu ulogu. Sjedilački organizmi poput spužvi i koralja izvor su brojnih biološki aktivnih spojeva zbog čega je bioprospecting mora važan za farmaceutsku, kozmetičku i druge industrije. Spojevi izolirani iz koralja Eunicella sp. mogu se klasificirati u tri skupine: terpenoidi, steroli te alkalodi i nukleozidi. Jedan od tih spojeva je indolni alkaloid granulatamid B koji je pokazao potencijalan inhibicijski učinak prema različitim ljudskim tumorskim stanicama. S obzirom da je važnost strukture indolnog prstena već prepoznata od strane farmaceutske industrije, sintetizirano je pet strukturnih analoga granulatamida B kojima su ispitani antioksidativni i antiproliferativni učinci koristeći redom ABTS i DPPH te MTT eseje. Spojevi su sintetizirani konjugacijom triptamina i nezasićenih masnih kiselina s ciljem nastanka amidne veze. Korištene masne kiseline su arahidonska, retinoična, palmitoleinska, oleinska i alfa-linolenska kiselina. Sinteza spojeva je potvrđena infracrvenom (IR) spektroskopijom, ultraljubičastom/vidljivom (UV-Vis) spektrofotometrijom, spektroskopijom nuklearne magnetske rezonancije (NMR) i spektrometrijom masa (MS). ABTS esej je ukazao na smanjenje antioksidativne aktivnosti kao posljedica vezanja masno-kiselinskog lanca osim u slučaju N-retinoiltriptamina. Potonje se može objasniti uz pretpostavku doprinosa sustava konjugiranih dvostrukih veza retinoične kiseline u inhibiciji spomenutog radikala. Nasuprot toga, DPPH esejom nisu uspješno utvrđena antioksidativna svojstva sintetiziranih spojeva. Dodatno, MTT esejom je uočeno kako svi sintetizirani spojevi pokazuju inhibitorni učinak prema staničnim linijama, među kojima je najaktivniji bio N-retinoiltriptamin. S druge strane, derivat alfa-linolenske kiseline je imao najslabiji učinak na normalnu staničnu liniju zbog čega bi oba navedena spoja trebalo dodatno strukturno modificirati. |
| Abstract (english) | One of the adaption strategies to the extreme environment developed by the marine organism is the synthesis of secondary metabolites. These compounds are not necessary for the growth, development and reproduction of the organisms but have an adaptive, defensive, signaling or some other roles. Sessile marine organisms, such are sponges and corals, present a source of numerous biologically active compounds, making sea bioprospecting important for the pharmaceutical, cosmetic and other industries. Compounds isolated from the corals of Eunicella sp. can be classified into three groups: terpenoids, sterols as well as alkaloids and nucleosides. One of these compounds is the indole alkaloid granulatamide B which has exerted a potential inhibitory activity towards various human cancer cell lines. Since the importance of the indole ring structure has already been recognized by the pharmaceutical industry, five structural analogs of granulatamide B have been synthesized, followed by evaluation of antioxidant and antiproliferative activities by DPPH/ABTS and MTT assays, respectively. The fatty acids which were used are: arachidonic, retinoic, palmitoleic, oleic and alpha-linolenic acids. The synthesis of the compounds was confirmed by infrared (IR) spectroscopy, ultraviolet-visible (UV-Vis) spectrophotometry, nuclear magnetic resonance (NMR) spectrometry and mass (MS) spectrometry. The antioxidant activity of synthesized compounds decreased as shown by ABTS assay as a consequence of fatty acids binding, except for N-retinoyltryptamine. The latter can be explained by the presence of conjugated double bonds in retinoic acid. Contrary, none of the examined analogues has been active in inhibition of DPPH radical. Furthermore, the results of MTT assay revealed that all analogues displayed antiproliferative activity against cancer cell lines, with N-retinoyltryptamine being the most active. However, derivative of alpha-linolenic acid was the least active against normal, non-transformed cell lines, therefore, both mentioned compounds should be considered for the further structural modification. |
