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- Title
Guanidines: Synthesis of Novel Histamine H 3 R Antagonists with Additional Breast Anticancer Activity and Cholinesterases Inhibitory Effect.
- Authors
Staszewski, Marek; Iwan, Magdalena; Werner, Tobias; Bajda, Marek; Godyń, Justyna; Latacz, Gniewomir; Korga-Plewko, Agnieszka; Kubik, Joanna; Szałaj, Natalia; Stark, Holger; Malawska, Barbara; Więckowska, Anna; Walczyński, Krzysztof
- 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.
- Subjects
GUANIDINES; BREAST; CHOLINESTERASES; ANTINEOPLASTIC agents; HISTAMINE; ALTERNATIVE treatment for cancer; ALZHEIMER'S disease
- Publication
Pharmaceuticals (14248247), 2023, Vol 16, Issue 5, p675
- ISSN
1424-8247
- Publication type
Article
- DOI
10.3390/ph16050675