Naslov
In vitro and In vivo activity of three novel monomethine cyanine derivatives - MCDs

Autori
Mišković, Katarina ; Belovari, Tatjana ; Rajc, Jasmina ; Šerić, Vatroslav ; Stojković, Ranko ; Piantanida, Ivo ; Baus Lončar, Mirela ; Glavaš-Obrovac, Ljubica

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
The Interplay of Biomolecules

Mjesto i datum
Zadar, Hrvatska, 24.09.2014. - 27.09.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
monomethine cyanine derivatives ; fluorescence ; visualization ; cytotoxicity ; cell cycle ; antitumor effect

Sažetak
Most of monomethine cyanine derivatives (MCDs) interact with nucleic acid by the minor groove DNA binding mechanism. An exception is investigated 2-[(1-cyano-4-methyl-(3H)-benzothiazol-[3, 2-a]-pyrido-2-lidene)-methyl]-3-methylbenzoxazole perchlorate (MCD 8) compound that interact with nucleic acids by intercalation mechanism. In this study, biological properties and applicative abilities of MCD derivatives were investigated. In vitro research methodology includes antiproliferative evaluation by MTT test on SCCVII, CT26.WT, 4T1, FsaR, and B16-F19 mouse tumour cell lines, cell cycle analysis by flow cytometry, MCDs entry and cellular localization by fluorescent microscopy, test of visualization of nucleic acids dyed with MCDs by gel electrophoresis, and MCDs application as detection dyes in a real time PCR method. Acute and chronic toxicity as well as antitumor effects were studied on the mouse model. Obtained results are analysed by Student t-test, multifactorial variance analysis (MANOVA) and Fisher LSD test in STATISTICA 8.0 program. The most sensitive was 4T1 mouse cell line on MCD 4 (IC50 = 0.9 µM) and FsaR on MCD 8 (IC50 = 8.4 µM). The cycle of HeLa cell was stopped by MCD 4 in G2/M phase, while MCD 8 stops it in S and G2/M phase. All analysed MCDs expressed characteristic green fluorescent signal spread all over the cell. Both MCD 4 and MCD 8 gave good results as possible detection dyes. MCD 4 is applicable for a real time PCR technique at the final concentration of a 0.51 µg/mL. MCD 8 (2 mg/mL) is a good choice in the visualization of nucleic acids on agarose gels. In vivo results pointed to stronger MCD 4 toxic effect in a chronic exposure to female in comparison to male mice. MCD 8 regarding to MCD 4 have lower toxicity with no difference among sexes and time of exposure. Tested compounds do not suppress the growth of implanted mouse mammary tumour. Study resulted with two new fluorescent monomethine cyanine dyes (MCD 4 and 8) of low toxicity with great application potential in the field of molecular biology for live cells denotation and biological molecular tracking.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

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