Bidentate ligands on osmium(VI) nitrido complexes control intracellular targeting and cell death pathways.

نویسندگان

  • Kogularamanan Suntharalingam
  • Timothy C Johnstone
  • Peter M Bruno
  • Wei Lin
  • Michael T Hemann
  • Stephen J Lippard
چکیده

The cellular response evoked by antiproliferating osmium(VI) nitrido compounds of general formula OsN(N^N)Cl3 (N^N = 2,2'-bipyridine 1, 1,10-phenanthroline 2, 3,4,7,8-tetramethyl-1,10-phenanthroline 3, or 4,7-diphenyl-1,10-phenanthroline 4) can be tuned by subtle ligand modifications. Complex 2 induces DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase, and caspase-dependent apoptotic cell death. In contrast, 4 evokes endoplasmic reticulum (ER) stress leading to the upregulation of proteins of the unfolded protein response pathway, increase in ER size, and p53-independent apoptotic cell death. To the best of our knowledge, 4 is the first osmium compound to induce ER stress in cancer cells.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Synthesis and antitumor activity of a series of osmium(VI) nitrido complexes bearing quinolinolato ligands.

A series of osmium(VI) nitrido complexes supported by quinolinolato ligands have been prepared and they exhibit promising in vitro anti-cancer activities. These results establish that Os(VI)≡N is a potentially versatile and promising platform for the design of a variety of high-valent anti-cancer drugs.

متن کامل

A Survey of Anticancer Effect of Some Five- and Six-Membered Palladium (II) Complexes (Containing Bidentate Phosphorus Ligands) on Caco-2 Colon Cancer Cell Line

Background and Objectives: Transition metal complexes possess a variety of biological and pharmacological activities, such as antitumor, antimicrobial, anti-inflammatory, anti-diabetic, and free radical scavenging. Many studies have been carried out on platinum-based chemotherapy agents, however, most attention has been paid to non-platinum metal-based agents in order to find different metal comp...

متن کامل

Osmium(vi) Complexes of Sulphonyl Amid0 Ligand. Crystal Structures Of

Interactions of [PPh4]2[0s02C14] and [Bu”,Nl[OsNCl~] with LiZL [H2L = 1,2bis(p-toluenesulphonylamido)benzene] gave binuclear osmium(V1) compounds (PPh,),[Osz 04LZ(p-OH)d (1) and OS~N~L&-OH)~ (2), respectively. The structures of both compounds have been determined by X-ray crystallography. The crystal structure of the [OsZ04LZ@0H),12anion contains two trans-0s02(L) units bridged by two OH groups...

متن کامل

(II) PREPARATION AND CHARACTERIZATION OF MN (III) COMPLEXES

We have prepared and characterized a few Mn (III) complexes by using a few bidentate and tridentate ligands. Spectra of the manganese (Abstract We have prepared and characterized a few Mn (III) complexes by using a few bidentate and tridentate ligands. Spectra of the manganese (III) ion in a variety of molecular environments are reported . On the basis of solution spectra, some of these co...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of the American Chemical Society

دوره 135 38  شماره 

صفحات  -

تاریخ انتشار 2013