Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents

Abstract

Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents, Bioorganic & Medicinal Chemistry (2010), doi: 10.1016/j.bmc.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. derived cell lines, whilst having no effect on 'normal' peripheral blood mononuclear cells. Such effects appear to be independent of the serotonin transporter, a high affinity target for amphetamines and independent of protein tyrosine phosphatases and tubulin dynamics both of which have been previously associated with nitrostyrene-induced cell death. We demonstrate that a number of these compounds induce caspase activation, PARP cleavage, chromatin condensation and membrane blebbing in a Burkitt's lymphoma-derived cell line, consistent with these compounds inducing apoptosis in vitro. Although no specific target has yet been identified for the action of these compounds, the cell death elicited is potent, selective and worthy of further investigation.

3’-hydroxy-4’-methoxy-β-methyl-β-nitrostyrene inhibits tumorigenesis in colorectal cancer cells through ROS-mediated DNA damage and mitochondrial dysfunction

“…Previous reports indicated that β-nitrostyrene derivatives exhibited anticancer activities via induction of apoptosis [8, 12, 32]. In agreement with these reports, our current data revealed that colorectal cancer cells treated with CYT-RX20 underwent caspase-associated apoptotic cell death.…”

The Synthetic β-Nitrostyrene Derivative CYT-Rx20 Inhibits Esophageal Tumor Growth and Metastasis via PI3K/AKT and STAT3 Pathways

“…β-nitrostyrene derivatives induced pro-apoptotic effect through inhibition of protein tyrosine phosphatases (PTPs) and phosphatases 2A (PP2A) [12,13] and inhibited the growth of cancer cells derived from stomach and immune responses of macrophages [6]. In addition, they induced the apoptosis in Burkitt's lymphoma derived cells via chromatin condensation and membrane blebbing [14]. The potent effects of β-nitrostyrene derivatives on inhibiting the TNFα-induced NF-κB survival pathway in a truncated retinoid X receptor α (tRXRα)-dependent manner resulted in a synergistic effect of β-nitrostyrene derivatives and TNFα on inducing breast cancer cell apoptosis [15].…”

Synthesis and antiproliferative action of a novel series of maprotiline analogues

“…Three of these compounds 56, 62 and 66 also displayed the ability to overcome M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT chemotherapeutic resistance due to drug efflux pumps. However, the significant antiproliferative and apoptotic effects of compound 56 on BL cell lines, together with a lack of toxicity against normal PBMCs suggests this nitrostyrene based compound as a potential lead compound in the development of new anticancer agents and warrants further investigation [43]. These results also demonstrate the importance of defining structureactivity relationships for novel compounds.…”

“…The nitrostyrene 62 compound, displayed the most potent activity for the DG-75 cell line with an EC 50 value of 1.5 µM. The potent antiproliferative effect of compound 62 on BL cell lines further suggests nitrostyrene based compounds as potential lead compounds in the development of new anticancer agents [43]. The styrene 49 was found to have no effect on the viability of DG-75 cells (>50 % cell viability at 100 µM), compared to the nitrostyrene 62, which displayed the most potent M A N U S C R I P T…”