Sinteza i biološka aktivnost (−)-kleinstenolida i njegovih analoga

Abstract

U ovom radu je ostvarena nova, višefazna sinteza prirodnog laktona (-)-kleistenolida (1) i njegovih odgovarajućih S-4, S-5 i S-6 analoga. Pored toga, ispitivana je biološka aktivnost novosintetizovanih analoga. Najznačajnija antiproliferativna aktivnost je uočena prema K562, Raji i A549 ćelijskim linijama, a većina sintetizovanih jedinjenja je ispoljila dobru aktivnost prema svim ispitivanim ćelijskim linijama. Pored citotoksičnosti, ispitana je i antimikrobna aktivnost novo-sintetizovanih analoga (-)- kleistenolida (1) gde je uočena dobra aktivnost inspitivanih jedinjenja. Na kraju je urađena i SAR analiza sa ciljem da se uporedi aktivnost novosintetizovanih analoga sa prirodnim proizvodom (-)- kleistenolidom (1) kako bi se imao uvid da li su primenjene uspešne strukturne modifikacije.

In this work, a new, multiphase synthesis of the natural lactone (-)- cleistenolide (1) and its corresponding C-4, C-5 and C-6 analogues was achieved. The biological activity of the newly synthesized analogues were tested. Тhe highest cytotoxicity effect was find against K562, Raja and A549 cell lines, and most of the synthetized compounds showed good activity against all tested cell lines. In addition, the antimicrobial activity of the new analogs was also tested, and it was found good activity of the tested compounds. At the end, it was performed a SAR analysis to compare the activity of the newly synthesized analogs with the natural product (-)- cleistenolide (1) to see if it has been successfully modified the structure.