Design, synthesis, and biological evaluation of a new class of benzo[b]furan derivatives as antiproliferative agents, with in silico predicted antitubulin activity

Synthesis and Biological Studies of Benzo[b]furan Derivatives: A Review from 2011 to 2022

“…Furthermore, some benzo[ b ]furan derivatives demonstrated anti-vascular properties [ 40 , 51 ], a significant aspect in tumoral angiogenesis. Several researchers have confirmed the predominant cell cycle arrest in the G2/M phase [ 37 , 41 , 44 , 46 , 48 , 49 , 51 ]. Notably, effects on the PI3K/Akt/mTOR signaling pathway have been observed [ 41 ], along with the inhibition of Top 1 DNA relaxation activity [ 52 ], suppression of SIRT3 histone deacetylase [ 53 ], mitigation of tumor cell metastasis as demonstrated in in vivo mouse assays [ 42 ], facilitation of the tumor resection process via bioluminescence monitoring [ 42 , 51 , 52 , 53 ], and anti-metastatic effects underscored by interleukin-25 secretion from tumor-associated fibroblasts (TAF) [ 42 ].…”

“…Similarly, Lauria et al conducted the synthesis of a novel series of 3-benzoylamino-5-(1 H -imidazol-4-yl)methylaminobenzo[ b ]furans 51 – 53 and subsequently evaluated their potential as antitumor agents [ 44 ]. The synthetic route involved a sequence of steps ( Scheme 9 ).…”

“…The biological studies focused on the antiproliferative activity in HeLa and MCF-7 cell lines using the MTT assay, cell cycle analysis, and in silico assessment [ 44 ]. Table 13 shows the GI 50 values of compounds 51a – f and 52a – f .…”

“…In the in silico studies, the researchers assessed the binding modes of each derivative at the colchicine binding site on tubulin, considering the involved amino acid residues [ 44 ]. To facilitate this analysis, they obtained the crystal structure of tubulin bound to colchicine from the PDB database (PDB ID code: 4O2B) and extracted the tubulin dimer with colchicine (chains A and B) from the protein model.…”

Synthesis and biological evaluation of quinoxaline derivatives as tubulin polymerization inhibitors that elevate intracellular ROS and triggers apoptosis via mitochondrial pathway

“…However, the clinical efficacy of the drugs is often limited by occurrence and evolution of resistance mechanisms that is further compounded by a narrow therapeutic index (Du et al., ; Gigant et al., ; Kavallaris, ; Perez, ; Wang, Chen, Miller, & Li, ; Wang et al., ). Recently, some colchicine binding tubulin inhibitors exhibit significant ability to overcome multidrug resistance (Bacher et al., ; Banerjee et al., ; Bueno et al., ; Cui et al., ; Dohle et al., ; Gangjee et al., ; Lauria et al., ; Li et al., ; Ohsumi et al., ; Pang et al., ; Suman et al., ). Even some drug candidates have already entered the clinical trial stage (Figure ).…”