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

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 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.

Recent biological applications of heterocyclic hybrids containings-triazine scaffold

“…In search of novel and potential antiproliferation agents, fused ring derivatives (50) of s -triazine and benzimidazole along with an appended oxazole ring linked via an amide bond were synthesized in high yield. 57 In vitro analysis against adenocarcinoma cell-lines and endothelial cell-line and IC 50 value was quite good for instance, Caco-2 = 19.36 ± 3.71 μM, HT-29 = 19.29 ± 2.62 μM, and HMVEC-d = 10.86 ± 0.08 μM. Further studies were done to insight into the mechanism of action of these drug candidates and it was investigated that the microtubule skeleton was targeted by these conjugates ( Table 1 ).…”