Background: Resveratrol (RES), an estrogen analog, is considered as a potential cancer chemopreventive agent. However, it remains unclear how RES is transported into cells. In this study, we observed that Caveolin-1(CAV1) expression can increase the cytotoxic and pro-apoptotic activity of RES in a dose-and time-dependent manner both in vitro and in vivo in a Hepatocellular Carcinoma animal model.

BCR-ABL is a gene produced by the fusion of the bcr gene and the c-abl protooncogene and is considered to be the main cause of chronic myelogenous leukemia (CML) production. Therefore, the development of selective Bcr-Abl kinase inhibitors is an attractive strategy for the treatment of CML. However, in the treatment of CML with a Bcr-Abl kinase inhibitor, the T315I gatekeeper mutant disrupts the important contact interaction between the inhibitor and the enzyme, resistant to the first-and second-generation drugs currently approved, such as imatinib, bosutinib, nilotinib, and dasatinib. In order to overcome this special resistance, several different strategies have been explored, and many molecules have been studied to effectively inhibit Bcr-Abl T315I. Some of these molecules are still under development, and some are being studied preclinically, and still others are in clinical research. Herein, this review reports some of the major examples of third-generation Bcr-Abl inhibitors against the T315I mutation.

A series of chrysin benzimidazole derivatives were synthesised and evaluated for their anticancer activity in the search for potential anticancer agents. Among them, compound 18 displayed the most potent anti-proliferative activity against MFC cells with IC values of 25.72 ± 3.95 μM. The flow cytometry results displayed that compound 18 induced apoptosis of MFC cells in a dose-dependent manner and caused the cell cycle to be arrested in the G0/G1 phase. Furthermore, the preliminary anticancer activity in vivo was also studied in tumour-bearing mice, and the compound 18 exerted good inhibition effect on tumour growth. These results suggested that compound 18 had good anticancer activity, which could be a potential anticancer agent after further optimisation and evaluation.

E‐DRS is a novel salvianolic acid A (SAA) analog, which was synthesized from resveratrol (RES) and methyldopate. Its structure is similar to that of SAA, but the 3′,4′‐dihydroxy‐trans‐stilbene group and the ester structure in SAA were replaced by the RES structure and an amine group, respectively. E‐DRS scavenged free oxygen radicals effectively, including superoxide anion (ascorbic acid > E‐DRS > SAA ≥ rutin > RES) and DPPH radical (rutin > E‐DRS ≥ ascorbic acid > SAA > RES), and exhibited powerful total antioxidant capacity (ascorbic acid > E‐DRS > SAA ≥ rutin > RES) in vitro. Furthermore, oral administration of E‐DRS dose‐dependently and significantly decreased CCl4‐induced oxidative stress in mice as indicated by the decreased content of hepatic malondialdehyde (MDA). In addition, oral administration of E‐DRS also increased the content of nonenzymatic antioxidant glutathione (GSH) and the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) in the liver of mice. All these results demonstrated that E‐DRS had good antioxidant activities both in vitro and in vivo, and could be a potential antioxidant agent after further optimization and evaluation.

With the development of exploration for disease‐related proteins or receptors, more and more novel structural lead compounds are required to designed and synthesized. The benzimidazole is an effective structural unit in which the benzene ring is fused at the 4 and 5 positions of the imidazole ring and wildly used in drug design. Here, we introduce some recent progress of research for anti‐tumor agents which was target to various target proteins such as DNA topoisomerase, angiogenesis, serine/threonine protein kinase, and tyrosine protein kinase. These anti‐tumor agents are all introduced benzimidazole as the structure unit. Further docking study showed that the benzimidazole group was not only act as a skeleton to expand the structure of molecule but also as an excellent ligand unit to form hydrogen bond or π–π conjugation and hydrophobic interaction with target proteins or receptors. We expect that introducing benzimidazole in the chemical structure could be a reasonable and priority strategy in novel anti‐tumor agents' design.

A series of 3',4',5'-trimethoxy flavonoids with benzimidazole linked by different chain alkanes have been designed and synthesized. The potential activity of these compounds as anti-tumor agents was evaluated by cytotoxicity assay in MGC-803 (human gastric cancer), MCF-7 (human breast cancer), HepG-2 (human hepatoma) and MFC (mouse gastric cancer) tumor cell lines. Among them, compound 7-(3-(2-chloro-1-benzo[]imidazol-1-yl)propoxy)-2-(3,4,5-trimethoxyphenyl)-4-chromen-4-one displayed the most potent antiproliferative activity, with IC values of 20.47 ± 2.07, 43.42 ± 3.56, 35.45 ± 2.03 μM and 23.47 ± 3.59 μM, respectively. The flow cytometry (FCM) results showed that compound caused the cell cycle to be arrested in G1 phase and induced apoptosis of MFC cells in a dose-dependent manner. In addition, compound exhibited a significant inhibitory effect on tumor growth . All the results outlined the great potential of compound for further exploitation as anti-tumor agent.

A series of flavonoid salicylate derivatives containing trimethoxybenzene and a series of chrysin salicylate derivatives were synthesized for use as anti-tumor agents, and evaluated for antiproliferative activity.

Although 1H‐benzo[d]imidazole‐4‐carboxamide derivatives have been explored for a long time, the structure–activity relationship of the substituents in the hydrophobic pocket (AD binding sites) has not thoroughly discovered. Here in, a series of 2‐(4‐[4‐acetylpiperazine‐1‐carbonyl]phenyl)‐1H‐benzo[d]imidazole‐4‐carboxamide derivatives have been designed, synthesized, and successful characterization as novel and effective poly ADP‐ribose polymerases (PARP)‐1 inhibitors to improve the structure–activity relationships about the substituents in the hydrophobic pocket. These derivatives were evaluated for their PARP‐1 inhibitory activity and cellular inhibitory against BRCA‐1 deficient cells (MDA‐MB‐436) and wild cells (MCF‐7) using PARP kit assay and MTT method. The results indicated that compared with other heterocyclic compounds, furan ring‐substituted derivatives 14n‐14q showed better PARP‐1 inhibitory activity. Among this derivatives, compound 14p displayed the strongest inhibitory effects on PARP‐1 enzyme (IC50 = 0.023 μM), which was close to that of Olaparib. 14p (IC50 = 43.56 ± 0.69 μM) and 14q (IC50 = 36.69 ± 0.83 μM) displayed good antiproliferation activity on MDA‐MB‐436 cells and inactivity on MCF‐7 cells, indicating that 14p and 14q have high selectivity and targeting. The molecular docking method was used to explore the binding mode of compound 14p and PARP‐1, and implied that the formation of hydrogen bond was essential for PARP‐1 inhibition activities. This study also showed that in the hydrophobic pocket (AD binding sites), the introduction of strong electronegative groups (furan ring, e.g.) or halogen atoms in the side chain of benzimidazole might improve its inhibitory activity and this strategy could be applied in further research.