2026-04-13T02:13:21Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1648422025-12-05T14:32:04Zcom_2072_1057col_2072_478917col_2072_478923

00925njm 22002777a 4500 dc Albert Mach, Joan author Bosque Pueyo, Ramón author Crespo, M. author Granell Sanvicente, Jaime Ramón author López Martínez, Ma. Concepción author Martín, Raquel author González, A. author Jayaraman, A. author Quirante Serrano, Josefina author Calvis, Carme author Badía Palacín, Josefa author Baldomà Llavinés, Laura author Font Bardia, Ma. Mercedes author Cascante i Serratosa, Marta author Messeguer i Peypoch, Ramon author 2020-06-08T18:20:00Z 2020-06-08T18:20:00Z 2015 2020-06-08T18:20:00Z The synthesis and preliminary biological evaluation of neutral and cationic platinum derivatives of chiral 1-(1-naphthyl)ethylamine are reported, namely cycloplatinated neutral complexes [PtCl{(R or S)-NH(2)CH(CH(3))C(10)H(6)}(L)] [L = SOMe(2) ( 1-R or 1-S ), L = PPh(3) (2-R or 2-S), L = P(4-FC(6)H(4))(3) (3-R), L = P(CH(2))(3)N(3)(CH(2))(3) (4-R)], cycloplatinated cationic complexes [Pt{(R)-NH(2)CH(CH(3))C(10)H(6)}{L}]Cl [L = Ph(2)PCH(2)CH(2)PPh(2) (5-R), L = (C(6)F(5))(2)PCH(2)CH(2)P(C(6)F(5))(2) (6-R)] and the Pt(ii) coordination compound trans-[PtCl(2){(R)-NH(2)CH(CH(3))C(10)H(6)}(2)] (7-R). The X-ray molecular structure of 7-R is reported. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), cell cycle arrest and apoptosis, DNA interaction, topoisomerase I and cathepsin B inhibition, and Pt cell uptake of the studied compounds are presented. Remarkable cytotoxicity was observed for most of the synthesized Pt(ii) compounds regardless of (i) the absolute configuration R or S, and (ii) the coordinated/cyclometallated (neutral or cationic) nature of the complexes. The most potent compound 2-R (IC(50) = 270 nM) showed a 148-fold increase in potency with regard to cisplatin in HCT-116 colon cancer cells. Preliminary biological results point out to different biomolecular targets for the investigated compounds. Neutral cyclometallated complexes 1-R and 2-R, modify the DNA migration as cisplatin, cationic platinacycle 5-R was able to inhibit topoisomerase I-promoted DNA supercoiling, and Pt(ii) coordination compound 7-R turned out to be the most potent inhibitor of cathepsin B. Induction of G-1 phase ( 2-R and 5-R ), and S and G-2 phases (6-R) arrests are related to the antiproliferative activity of some representative compounds upon A-549 cells. Induction of apoptosis is also observed for 2-R and 6-R. Platí Càncer Platinum Cancer Neutral and ionic platinum compounds containing a cyclometalated chiral primary amine: Synthesis, antitumor activity, DNA interaction and topoisomerase I - cathepsin B inhibition