News Column

Studies from National University Yield New Data on Medicinal Chemistry (Synthesis and cholinesterase inhibition of cativic acid derivatives)

September 5, 2014

By a News Reporter-Staff News Editor at Health & Medicine Week -- Investigators publish new report on Health and Medicine. According to news reporting originating in Buenos Aires, Argentina, by NewsRx journalists, research stated, "Alzheimer's disease (AD) is a neurodegenerative disorder associated with memory impairment and cognitive deficit. Most of the drugs currently available for the treatment of AD are acetylcholinesterase (AChE) inhibitors."

The news reporters obtained a quote from the research from National University, "In a preliminary study, significant AChE inhibition was observed for the ethanolic extract of Grindelia ventanensis (IC50 = 0.79 mg/mL). This result prompted us to isolate the active constituent, a normal labdane diterpenoid identified as 17-hydroxycativic acid (1), through a bioassay guided fractionation. Taking into account that 1 showed moderate inhibition of AChE (IC50 = 21.1 mu M), selectivity over butyrylcholinesterase (BChE) (IC50 = 171.1 mu M) and that it was easily obtained from the plant extract in a very good yield (0.15% w/w), we decided to prepare semisynthetic derivatives of this natural diterpenoid through simple structural modifications. A set of twenty new cativic acid derivatives (3-6) was prepared from 1 through transformations on the carboxylic group at C-15, introducing a C2-C6 linker and a tertiary amine group. They were tested for their inhibitory activity against AChE and BChE and some structure activity relationships were outlined. The most active derivative was compound 3c, with an IC50 value of 3.2 mu M for AChE. Enzyme kinetic studies and docking modeling revealed that this inhibitor targeted both the catalytic active site and the peripheral anionic site of this enzyme."

According to the news reporters, the research concluded: "Furthermore, 3c showed significant inhibition of AChE activity in SH-SY5Y human neuroblastoma cells, and was non-cytotoxic."

For more information on this research see: Synthesis and cholinesterase inhibition of cativic acid derivatives. Bioorganic & Medicinal Chemistry, 2014;22(15):3838-3849. Bioorganic & Medicinal Chemistry can be contacted at: Pergamon-Elsevier Science Ltd, The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, England. (Elsevier -; Bioorganic & Medicinal Chemistry -

Our news correspondents report that additional information may be obtained by contacting N.P. Alza, Univ Nacl Gen San Martin, Escuela Ciencia & Tecnol, RA-1650 Buenos Aires, DF, Argentina. Additional authors for this research include V. Richmond, C.J. Baier, E. Freire, R. Baggio and A.P. Murray (see also Health and Medicine).

Keywords for this news article include: Argentina, Buenos Aires, South America, Health and Medicine

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Source: Health & Medicine Week

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