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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/168258

Cyclopalladated Benzophenone Imines: Synthesis, Antitumor Activity, Cell Accumulation, DNA Interaction, and Cathepsin B Inhibition.

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The synthesis of the endo five-membered cyclo-ortho-palladated benzophenone imines [Pd{C6H4(Ph)C═NR}]2(μ-X)2 [1 (X = OAc), 2 (X = Cl), a (R = phenyl), b (R = 1-naphthyl), c (R = benzyl), d (R = α-methylbenzyl)], and trans-N,P-[Pd{C6H4(Ph)C═NR}X(PPh3)] [3 (X = OAc), 4 (X = Cl), a (R = phenyl), b (R = 1-naphthyl), c (R = benzyl), d (R = α-methylbenzyl)] and the X-ray molecular structure of 1a, 1c, 1d, 4a, 4b, and 4c are reported. The antitumor activity, DNA interaction, and cathepsin B inhibition of palladium compounds a-d were studied and compared with those previously reported for palladium compounds e with R = H and compound 4f analogous to 4e but with a platinum(II) center. The IC50 values against a panel of human cancer cell lines allowed the establishment of a qualitative relationship between their structure and antitumor activity. Compounds 3e, 4e, and 4f were the most active ones in relation to their in vitro anticancer activity. Compounds 3e and 4e were about 4 times more active than cisplatin against the MDA-MB-231 and MCF-7 breast human cancer lines, and compound 4f was about 4 times more active than cisplatin against the cisplatin-resistant HCT-116 colon human cancer cell line. In addition, compound 3e was 3 times less cytotoxic than cisplatin toward the quiescent HUVEC cells. Accumulation of palladium compounds e and b in the MDA-MB-231 cell line was considerably greater than that of cisplatin in the same cell line, but palladium compounds b were noncytotoxic. Some of these complexes altered the DNA tertiary structure in a similar way to cisplatin but at higher concentration, and most cytotoxic ones did not present a high efficiency as cathepsin B inhibitors.

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ALBERT MACH, Joan, et al. Cyclopalladated Benzophenone Imines: Synthesis, Antitumor Activity, Cell Accumulation, DNA Interaction, and Cathepsin B Inhibition. Organometallics. 2014. Vol. 33, num. 24, pags. 7284-7292. ISSN 0276-7333. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/168258

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