New antiproliferative agents derived from tricyclic 3,4-dihydrobenzo[4,5]imidazo[1,2-a][1,3,5]triazine scaffold: Synthesis and pharmacological effects.

Autor: Robello M; Synthetic Bioactive Molecules Section, LBC, NIDDK, NIH, Bethesda, Maryland, USA., Salerno S; Department of Pharmacy, University of Pisa, Pisa, Italy.; Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Pisa, Italy., Barresi E; Department of Pharmacy, University of Pisa, Pisa, Italy.; Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Pisa, Italy., Orlandi P; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Vaglini F; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy., Banchi M; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Simorini F; Department of Pharmacy, University of Pisa, Pisa, Italy., Baglini E; Department of Pharmacy, University of Pisa, Pisa, Italy., Poggetti V; Department of Pharmacy, University of Pisa, Pisa, Italy., Taliani S; Department of Pharmacy, University of Pisa, Pisa, Italy.; Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Pisa, Italy., Da Settimo F; Department of Pharmacy, University of Pisa, Pisa, Italy.; Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Pisa, Italy., Bocci G; Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Pisa, Italy.; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2022 Nov; Vol. 355 (11), pp. e2200295. Date of Electronic Publication: 2022 Jul 29.
DOI: 10.1002/ardp.202200295
Abstrakt: A series of novel 3,4-dihydrobenzo[4,5]imidazo[1,2-a][1,3,5]triazine (BIT) derivatives were designed and synthesized. In vitro antiproliferative activity was detected toward two human colorectal adenocarcinoma cell lines (CaCo-2 and HT-29) and one human dermal microvascular endothelial cell line (HMVEC-d). The most active compounds, namely 2-4 and 8, were further investigated to clarify the mechanism behind their biological activity. Through immunofluorescence assay, we identified the target of these molecules to be the microtubule cytoskeleton with subsequent formation of dense microtubule accumulation, particularly at the periphery of the cancer cells, as observed in paclitaxel-treated cells. Overall, these results highlight BIT derivatives as robust and feasible candidates deserving to be further developed in the search for novel potent antiproliferative microtubule-targeting agents.
(© 2022 The Authors. Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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