Cytotoxicity of the traditional chinese medicine (TCM) plumbagin in its copper chemistry

Abstract

The anticancer traditional Chinese medicine (TCM), plumbagin (PLN), was isolated from Plumbago Zeylanica. Reaction of plumbagin with Cu(II) salt, afforded [Cu(PLN)(2)].2H(2)O (1). With 2,2'-bipyridine (bipy) as a co-ligand, PLN reacts with Cu(II) to give [Cu(PLN)(bipy)(H(2)O)](2)(NO(3))(2).4H(2)O (2). 1 and 2 were characterized by elemental analysis, IR, ESI-MS spectra. Their crystal structures were determined by single crystal X-ray diffraction methods. The in vitro cytotoxicity of PLN, 1 and 2 against seven human tumour cell lines was assayed. The metal-based compounds exhibit enhanced cytotoxicity vs. that of free PLN, suggesting that these compounds display synergy in the combination of metal ions with PLN. The binding properties of PLN, 1 and 2 to DNA were investigated through UV-vis, fluorescence, CD spectra, and gel mobility shift assay, which indicated that 1 and 2 were non-covalent binding and mainly intercalated the neighboring base pairs of DNA. PLN, 1 and 2 exhibit inhibition activity to topoisomerase I (TOPO I), but 1 and 2 were more effective than PLN.

Isoquinoline derivatives Zn(II)/Ni(II) complexes: Crystal structures, cytotoxicity, and their action mechanism

“…Especially those complexes that one metal centre chelates two same planar aromatic ligands in trans mode. They induced apoptosis of the tumour cells through damaging DNA [27][28][29]. To continue our work on the antitumor metal complexes with 4,5-methylenedioxy-1-pyridinedihydroiso -quinoline (MPDQ) and 5-pyridin-2-yl- [1,3]dioxolo [4,5-g] isoquinoline (PYP), herein, we reported the synthesis, characterization, in vitro cytotoxicity of two isoquinoline-zinc(II) and one nickel(II) complexes, and the possible anticancer mechanisms.…”

Synthesis, characterization and preliminary cytotoxicity evaluation of five Lanthanide(III)–Plumbagin complexes

“…Among them, new coordination compounds based on the traditional Chinese medicines (TCMs) provide a novel approach to potential (pro-)drugs [16][17][18][19][20][21][22][23], which have been recently reviewed by Chen and Liang [24].…”

Investigação de reatividade de miméticos de tirosinase na viabilidade celular de melanomas

“…Além disso, esses complexos podem ter como alvo a mitocôndria [56], atuando como agentes desacopladores, isto é, diminuindo o potencial da membrana interna da mitocôndria e interrompendo a síntese do ATP [57]. Compostos deste tipo podem ainda atuar como inibidores de proteínas envolvidas no controle do ciclo celular, como as kinases, por exemplo a AMPK [58], ou envolvidas em mecanismos de reparo aos ácidos nucléicos, como as topoisomerases [59]. Dessa forma, busca-se aprofundar e desvendar o verdadeiro modo de ação destes complexos, que desencadeia a cascata de eventos que levam células tumorais à apoptose.…”

“…Um hipocromismo, caracterizado por uma diminuição na intensidade de absorção em 260 nm poderia ser observado, devido às intercalações π-π de tunelamento dos grupos aromáticos dos ligantes com DNA, um hipercromismo com pontos isosbésticos e até um batocromismo também poderia ocorrer [59], havendo interação eficiente entre os complexos estudados e o DNA.…”

“…Estes estudos mostraram que compostos podem interagir com o DNA de várias formas, muitas vezes moduladas pelo ligante do complexo, assim, estudos espectroscópicos podem nos dar indícios dos possíveis mecanismos de ação dos complexos, bem como seu modo de interação com o DNA [133]. [59]. Figura 54.…”