Phenyl-substituted aminomethylene-bisphosphonates inhibit human P5C reductase and show antiproliferative activity against proline-hyperproducing tumour cells.

Journal of Enzyme Inhibition and Medicinal Chemistry
Giuseppe ForlaniMonica Borgatti

Abstract

In certain cancers, such as breast, prostate and some lung and skin cancers, the gene for the enzyme catalysing the second and last step in proline synthesis, δ1-pyrroline-5-carboxylate (P5C) reductase, has been found upregulated. This leads to a higher proline content that exacerbates the effects of the so-called proline-P5C cycle, with tumour cells effectively using this method to increase cell survival. If a method of reducing or inhibiting P5C reductase could be discovered, it would provide new means of treating cancer. To address this point, the effect of some phenyl-substituted derivatives of aminomethylene-bisphosphonic acid, previously found to interfere with the catalytic activity of plant and bacterial P5C reductases, was evaluated in vitro on the human isoform 1 (PYCR1), expressed in E. coli and affinity purified. The 3.5-dibromophenyl- and 3.5-dichlorophenyl-derivatives showed a remarkable effectiveness, with IC50 values lower than 1 µM and a mechanism of competitive type against both P5C and NADPH. The actual occurrence in vivo of enzyme inhibition was assessed on myelogenous erythroleukemic K562 and epithelial breast cancer MDA-MB-231 cell lines, whose growth was progressively impaired by concentrations of the dib...Continue Reading

References

Oct 15, 1976·International Journal of Cancer. Journal International Du Cancer·E KleinF Vánky
Jan 1, 1985·Current Topics in Cellular Regulation·J M Phang
Apr 1, 1981·The Journal of Clinical Investigation·G C YehJ M Phang
May 27, 2004·Journal of Agricultural and Food Chemistry·Agnieszka ObojskaGiuseppe Forlani
Apr 8, 2006·Protein Expression and Purification·Zhaohui MengZihe Rao
Jul 29, 2006·Molecular and Cellular Biochemistry·Chien-an A HuJames M Phang
May 4, 2007·Journal of Agricultural and Food Chemistry·Giuseppe ForlaniPaweł Kafarski
Apr 11, 2008·Journal of Agricultural and Food Chemistry·Giuseppe ForlaniPaweł Kafarski
Sep 23, 2008·The Journal of Nutrition·James M PhangYongmin Liu
Aug 22, 2009·Pest Management Science·Andrea OcchipintiGiuseppe Forlani
Aug 14, 2012·BioFactors·Wei Liu, James M Phang
Jun 25, 2013·Journal of Agricultural and Food Chemistry·Giuseppe ForlaniPaweł Kafarski
Aug 4, 2015·Journal of Enzyme Inhibition and Medicinal Chemistry·Paulina KosikowskaŁukasz Berlicki
Aug 19, 2015·Frontiers in Plant Science·Gudrun WinterDietmar Funck
Jul 3, 2016·Cold Spring Harbor Protocols·Lisa C CrowleyNigel J Waterhouse
Mar 5, 2017·The Journal of Biological Chemistry·Emily M ChristensenJohn J Tanner
Sep 25, 2017·Cell Chemical Biology·Alba LuengoMatthew G Vander Heiden
Oct 11, 2017·Antioxidants & Redox Signaling·James M Phang
Apr 13, 2018·Biochemistry·John J TannerDonald F Becker
Aug 1, 2019·Bioorganic & Medicinal Chemistry Letters·Kirsty MilneReuven Agami
Aug 21, 2019·Open Medicine·Qiu-Li Wang, Ling Liu
Sep 11, 2019·Journal of Experimental Botany·Alban LaunayArnould Savouré
Jun 6, 2020·Frontiers in Oncology·Cristina D'AnielloGabriella Minchiotti
Nov 17, 2020·Frontiers in Plant Science·Giuseppe Forlani, Dietmar Funck

❮ Previous
Next ❯

Citations

Aug 31, 2021·Frontiers in Cell and Developmental Biology·Eduardo J PatriarcaGabriella Minchiotti

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.