engleski

Conformation and self assembling of quinoline-ferrocene conjugates

Tremendous progress in the incorporation of organometallic fragments into biomolecules to provide compounds with anticancer activity has been observed in recent years. Among bioactive organometallic compounds, iron‐containing metallocenes, ferrocenes conjugated with biologically active compounds, have been found to exhibit promising cytostatic effects [1]. Furthermore, ferrocifen compounds were developed as ferrocenyl analogs of tamoxifen, a known antagonist of estrogen receptor in breast cancer. Compared with tamoxifen, ferrocifens possessed not only endocrine‐modulating properties, but also cytotoxic effects against estrogen-independent breast cancer. On the other hand, quinoline and quinolone scaffolds play an important role in anticancer drug development as their derivatives have shown activity through diverse mechanisms of action, such as growth inhibitors by cell cycle arrest, apoptosis, abrogation of cell migration, inhibition of angiogenesis and disregulation of nuclear receptor signaling [2]. Recently, we have described the synthesis of novel ferrocene-quinoline and quinolone conjugates, and evaluated their cytostatic and antioxidant activities [3]. The 6-chloro-4-[2-(4-ferrocenyl-1, 2, 3-triazol-1-yl)ethoxy]-2-(trifluoromethyl) quinoline (1), with selective inhibitory activity on Raji cells (IC50 = 7.9 µM) and no cytostatic effect on normal MDCK1 cells, was highlighted as the most promising anticancer organometallic complex in a group of O-alkylated quinolines. In this work we report structures of two ferrocene-quinoline conjugates, 6-chloroquinoline-ferrocene conjugate 1 and 4-[2-(4-ferrocenyl-1, 2, 3-triazol-1-yl)ethoxy]-2-(trifluoromethyl) quinoline (2), with focus on self-assembly of the molecules (Figure 1) and their conformation. [1] K. Kowalski, Coord. Chem. Rev. 366 (2018) 91-108. [2] O. Afzal, S. Kumar, M.R. Haider, M.R. Ali, R. Kumar, M. Jaggi, S. Bawa, Eur. J. Med. Chem. 97 (2015) 871-910. [3] S. Maračić, J. Lapić, S. Djaković, T. Opačak-Bernardi, Lj. Glavaš-Obrovac, V. Vrček, S. Raić‐Malić, Appl. Organometal. Chem. 33 (2019) e4628.

ferrocenes ; quinolines ; self-assembly ; conformation

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