Synthesis and antitumor activity of benzils related to combretastatin A-4

Abstract

A series of benzil derivatives related to combretastatin A-4 (CA-4) have been synthesized by oxidation of diarylalkynes promoted by PdI(2) in DMSO. Using this new protocol, 14 benzils were prepared in good to excellent yields and their biological activity has been delineated. Several benzils exhibited excellent antiproliferative activity: for example, 4j and 4k bearing the greatest resemblance to CA-4 and AVE-8062, respectively, were found to inhibit cell growth at the nanomolar level (20-50nM) on four human tumor cell lines. Flow cytometric analysis indicates that these compounds act as antimitotics and arrest the cell cycle in G(2)/M phase. A cell-based assay indicated that compounds 4j and 4k displayed a similar inhibition of tubulin assembly with an IC(50) value similar to CA-4. These results clearly demonstrated that the Z-double bond of CA-4 can be replaced by a 1,2-diketone unit without significant loss of cytotoxicity and inhibition of tubulin assembly potency.

Discovery of Isoerianin Analogues as Promising Anticancer Agents

“…[7] Despite the remarkable anticancer activity of these stilbenes, the Z-configured double bond is prone to isomerization to the more thermally stable E isomer during storage and administration, resulting in a dramatic loss of cytotoxicity. As a part of our search for novel tubulin polymerization inhibitors, [9,10] we recently synthesized and evaluated the biological properties of a new series of 1,1-diarylethylene derivatives with general structure 2 ( Figure 1). Several compounds exhibited excellent antiproliferative activity at nanomolar concentrations against a panel of human cancer cell lines.…”

“…This reinforces the bioisosteric replacement approach in the combretastatin series previously reported by our research group. As a part of our search for novel tubulin polymerization inhibitors, [9,10] we recently synthesized and evaluated the biological properties of a new series of 1,1-diarylethylene derivatives with general structure 2 ( Figure 1). [11] We demonstrated that bioisosteric replacement of the (Z)-1,2-ethylene portion with a 1,1-ethylene bridge resulted in retention of biological activities.…”

Tuning the Emission Colour of Triphenylamine‐Capped Cyclometallated Platinum(II) Complexes and Their Application in Luminescent Oxygen Sensing and Organic Light‐Emitting Diodes

“…This is probably due to Pt-catalysed oxidation of the -CϵC-bonds. [40,41] All the intermediates and the final Pt complexes were obtained in satisfactory yields.…”

Nanosized Mn(acac)3 Anchored on Amino Functionalized Silica for the Selective Oxidative Synthesis of 2-arylbenzimidazoles, 2-arylbenzothiazoles and Aerobic Oxidation of Benzoins in Water

“…In many of the methods for the synthesis of benzimidazoles or benzothiazoles, stoichiometric amounts of oxidizing agents such as amino-acid based prolinium nitrate ionic liquid [42], K 3 Fe(CN) 6 at 90°C under basic conditions [43]; excess of Mn(OAc) 3 [46] have reported environmentally benign method for the synthesis of 2-arylbenzothiazoles in water at 110°C. The oxidation of benzoins to benzils is an important synthetic transformation in organic synthesis because of their applications as photosensitive and synthetic agents in organic and pharmaceutical chemistry [47][48][49][50][51][52]. The most straight forward method for the synthesis of benzils is the oxidation of benzoins.…”