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 immuno fluorescence 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.

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

Silvia Salerno
Secondo
;
Elisabetta Barresi;Francesca Vaglini;Francesca Simorini;Valeria Poggetti;Sabrina Taliani
;
Federico Da Settimo
Penultimo
;
Guido Bocci
Ultimo
2022-01-01

Abstract

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 immuno fluorescence 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
Robello, Marco; Salerno, Silvia; Barresi, Elisabetta; Orlandi, Paola; Vaglini, Francesca; Banchi, Marta; Simorini, Francesca; Baglini, Emma; Poggetti, Valeria; Taliani, Sabrina; DA SETTIMO PASSETTI, Federico; Bocci, Guido
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1149543
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