Embarek Bentouhami

Natural products have historically been a mainstay source of anticancer drugs, but in the 90's they fell out of favor in pharmaceutical companies with the emergence of targeted therapies, which rely on antibodies or small synthetic molecules identified by high throughput screening. Although targeted therapies greatly improved the treatment of a few cancers, the benefit has remained disappointing for many solid tumors, which revitalized the interest in natural products. With the approval of rapamycin in 2007, 12 novel natural product derivatives have been brought to market. The present review describes the discovery and development of these new anticancer drugs and highlights the peculiarities of natural product and new trends in this exciting field of drug discovery.

The clinical success of cisplatin has stimulated the quest for novel anticancer metallodrugs during the last two decades. A major emphasis has been put on copper due to its selective cytotoxicity toward malignant cells. This selectivity stems from the hypoxic environment of cancer cells that promotes the reduction of Cu(II) to Cu(I), leading a pro-apoptotic oxidative stress. At the current time, two copper complexes have reached clinical assay, which paves the road to the first copper-based anticancer therapeutics.

The present work reports the hydrolysis of ions of the series of lanthanides (III) and actinide (IV) elements in dilute aqueous solutions. It has been systematically examined in the presence of sodium perchlorate, which has been used for maintaining the solution at constant ionic strength. The number, the nature of the species in solution and their hydrolysis constants log β 10i for all ions at I = 0.1 mol dm –3 and at 25 °C were determined by different softwares: Superquad and Sirko_P. A pH-potentiometric method was used with glass electrodes to determine the equilibrium constants K i : <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" mode="display"> <mml:mrow> <mml:msup> <mml:mi>M</mml:mi> <mml:mi>n</mml:mi> </mml:msup> <mml:mo>+</mml:mo> <mml:msub> <mml:mi mathvariant="normal">H</mml:mi> <mml:mn>2</mml:mn> </mml:msub> <mml:mi mathvariant="normal">O</mml:mi> <mml:mo>⇌</mml:mo> <mml:mi mathvariant="normal">M</mml:mi> <mml:msup> <mml:mrow> <mml:mo>(</mml:mo> <mml:mi>OH</mml:mi> <mml:mo>)</mml:mo> </mml:mrow> <mml:mrow> <mml:mo>(</mml:mo> <mml:mi mathvariant="normal">n</mml:mi> <mml:mo>-</mml:mo> <mml:mn>1</mml:mn> <mml:mo>)</mml:mo> <mml:mo>+</mml:mo> </mml:mrow> </mml:msup> <mml:mo>+</mml:mo> <mml:msup> <mml:mi mathvariant="normal">H</mml:mi> <mml:mo>+</mml:mo> </mml:msup> </mml:mrow> </mml:math> where M n + represents Ce 3+ , Pr 3+ , Nd 3+ , Eu 3+ , Sm 3+ and Th 4+ ions. For the lanthanides, hydrolysis increases with the increase of the atomic number and the contraction of the ionic radius. The Th 4+ ion undergoes significant hydrolysis.