| Title |
From natural products to synthetic analogues: pyrrole-pyrazole exchange in lamellarin O / |
| Authors |
Dzedulionytė, K ; Fuxreiter, N ; Schreiber-Brynzak, E ; Žukauskaitė, A ; Pichler, V ; Arbačiauskienė, E |
| DOI |
10.15388/CCT.2023 |
| ISBN |
9786090708330 |
| Full Text |
|
| Is Part of |
Chemistry and chemical technology: international conference CCT-2023, March 10, 2023, Vilnius: conference book.. Vilnius : Vilnius university press, 2023. P 019, p. 56.. ISBN 9786090708330 |
| Abstract [eng] |
Lamellarins are a group of natural marine-derived alkaloids with a characteristic central pyrrole moiety and widely reported biological activity. Since their discovery in 1985, more than 50 compounds of this family have been isolated from various marine organisms, such as sponges or ascidians [1]. The biological spectrum of lamellarins is manifold, with pronounced cytotoxic activity [2],[3]. For example, lamellarin D, a leading compound in the family, induces its anticancer activity through topoisomerase I inhibition and mitochondrial targeting that triggers cell death [4]. Whereas lamellarin O was reported to exhibit moderate cytotoxicity against colorectal cancer SW620 and its multi-drug resistant daughter cell line SW620/Ad300 [5]. The structure of lamellarin O is easily accessible for replacement of the central pyrrole ring to design new derivatives with structural similarities like shape and electronic configuration by other five membered ring systems. Pyrazole is a versatile moiety taking place in various biologically active compounds as well as in-use pharmaceuticals [6]. Replacement of the central pyrrole to pyrazole is expected to change e.g., the energy of the highest occupied molecular orbital which is associated with increased metabolic stability [7]. In this study it was ought to synthesize and investigate various functionalized pyrazole derivatives of lamellarin O. The goal was based on the scaffold hopping of the pyrrole ring in natural lamellarin O to its pyrazole counterpart. Obtained compounds were evaluated for their physicochemical properties and further investigated as potent agents against human colon cancer cell lines HCT116, HT29 and SW480. Moreover, after structureactivity relationship determination, the most cytotoxic compounds were used to investigate their mode of action in the beforementioned cell lines. |
| Published |
Vilnius : Vilnius university press, 2023 |
| Type |
Conference paper |
| Language |
English |
| Publication date |
2023 |
| CC license |
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