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Updated: Jul 29, 2025

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products
Published on: September 9, 2016
Guanidines: Synthesis of Novel Histamine H3R Antagonists with Additional Breast Anticancer Activity and
Marek Staszewski1, Magdalena Iwan2, Tobias Werner3
1Department of Synthesis and Technology of Drugs, Medical University of Lodz, Muszyńskiego 1, 90-151 Łódź, Poland.
Abstract:
This study examines the properties of novel guanidines, designed and synthesized as histamine H3R antagonists/inverse agonists with additional pharmacological targets. We evaluated their potential against two targets viz., inhibition of MDA-MB-231, and MCF-7 breast cancer cells viability and inhibition of AChE/BuChE. ADS10310 showed micromolar cytotoxicity against breast cancer cells, combined with nanomolar affinity at hH3R, and may represent a promising target for the development of an alternative method of cancer therapy. Some of the newly synthesized compounds showed moderate inhibition of BuChE in the single-digit micromolar concentration ranges. H3R antagonist with additional AChE/BuChE inhibitory effect might improve cognitive functions in Alzheimer's disease. For ADS10310, several in vitro ADME-Tox parameters were evaluated and indicated that it is a metabolically stable compound with weak hepatotoxic activity and can be accepted for further studies.
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