Novel tetranuclear Pd-II and Pt-II anticancer complexes derived from pyrene thiosemicarbazones

Autor(es)

Oliveira, Carolina G. ^{[1, 2, 3]} ; Romero-Canelon, Isolda ^[4] ; Coverdale, James P. C. ^[2] ; Maia, Pedro Ivo S. ^[5] ; Clarkson, Guy J. ^[2] ; Deflon, Victor M. ^[3] ; Sadler, Peter J. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Uberlandia, Inst Chem, BR-38400902 Uberlandia, MG - Brazil

^[2] Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands - England

^[3] Univ Sao Paulo, Sao Carlos Inst Chem, BR-13560970 Sao Carlos - Brazil

^[4] Univ Birmingham, Sch Pharm, Birmingham B15 2TT, W Midlands - England

^[5] Univ Fed Triangulo Mineiro, Dept Chem, BR-38025440 Uberaba - Brazil

• Tipo de documento: Artigo Científico
• Fonte: DALTON TRANSACTIONS; v. 49, n. 28, p. 9595-9604, JUL 28 2020.
• Citações Web of Science: 1

Resumo

Cyclometallated palladium(II) and platinum(II) pyrenyl-derived thiosemicarbazone (H2PrR) complexes of the type {[}M-4(mu-S-PrR-kappa(3)-C,N,S)(4)] (M = Pd-II, Pt-II; R = ethyl, cyclohexyl) have been synthesised in good yields and fully characterised. X-ray crystallography showed that the tetranuclear complex {[}Pt-4(mu-S-PrCh-kappa(3)-C,N,S)(4)](CH3)(2)COCHCl3 contains an eight-membered ring of alternating M-S atoms. The ethyl derivatives {[}M-4(mu-S-PrEt-kappa(3)-C,N,S)(4)] exhibit potent antiproliferative activity towards A2780 human ovarian cancer cells, with IC50 values of 1.27 mu M (for M = Pd-II) and 0.37 mu M ( for M = Pt-II), the latter being an order of magnitude more potent than the anticancer drug cisplatin (IC50 1.20 mu M). These promising complexes had low toxicity towards non-cancerous human MRC5 cells, which points towards an early indication of differential toxicity between cancer and normal cells. Experiments that investigated the effects of these tetranuclear complexes on the cell cycle, integrity of the cell membrane, and induction of apoptosis, suggested that their mechanism of action of does not involve DNA targeting, unlike cisplatin, and therefore could be promising for combatting cisplatin resistance. (AU)

• Processo FAPESP: 09/54011-8 - EMU: aquisição de difratômetro de raios X de monocristal para análise estrutural de moléculas pequenas e proteínas
• Beneficiário: Victor Marcelo Deflon
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários