Design, Synthesis, and Biological Evaluation of (E)-Styrylbenzylsulfones as Novel Anticancer Agents

Abstract

Cell cycle progression is regulated by cyclins and cyclin-dependent kinases, which are formed at specific stages of the cell cycle and regulate the G1/S and G2/M phase transitions, employing a series of "checkpoints" governed by phosphorylation of their substrates. Tumor development is associated with the loss of these checkpoint controls, and this provides an approach for the development of therapeutic agents that can specifically target tumor cells. Here, we describe the synthesis and SAR of a novel group of cytotoxic molecules that selectively induce growth arrest of normal cells in the G1 phase while inducing a mitotic arrest of tumor cells resulting in selective killing of tumor cell populations with little or no effect on normal cell viability. The broad spectrum of antitumor activity in vitro and xenograft models, lack of in vivo toxicity, and drug resistance suggest potential for use of these agents in cancer therapy.

Synthesis and Evaluation of Azetidinone Analogues of Combretastatin A-4 as Tubulin Targeting Agents

“…is also in clinical trials as a water soluble amino acid prodrug (3b, figure 1) 17 . In contrast to colchicine, the anti-vascular effects of 2a in vivo are apparent well below the maximum tolerated dose, offering a wide therapeutic window.…”

Synthesis and biological evaluation of benzyl styrylsulfonyl derivatives as potent anticancer mitotic inhibitors

“…This was consistent with ON 01910 mechanism of action described previously. 15,3 Compound 7 demonstrated a similar cell-cycle profile; treatment of the cells with 7 at 0.5 μM (GI 50 ) and 1.0 M (2xGI 50 ) causing 77 % and 85 % cells with G2/M DNA content respectively.…”

A Quantum Chemical and Chemometrical Study of Styrylbenzylsulfones and their Analogues with Citotoxic Activity against Prostate Cancer Cells

“…The IC 50 values estimated by Reddy 13 were used in this work and are showed in Table 1. From 34 molecule studied, 14 compounds have been observed to be inactive against prostate cancer cell lines (IC 50 > 20 M), while the remaining compounds have been considered inactive.…”

“…6-11 The present work investigated the relationship between the geometric and electronic properties and the activity of a group of 34 compounds of Styrylbenzylsulfones 12 reported in the literature as presenting a certain degree of anti-prostate cancer [13][14][15][16] by using quantum chemistry methods to calculate molecular descriptors. Multivariate statistical methods were used to analyze and classify a data set of the molecules into groups that can be correlated to their activity.…”