Numerous reports have shown that conjugated benzimidazole derivatives possess various kinds of biological activities, including anticancer properties. In this report, we designed and synthesized 24 new molecules comprising a benzimidazole ring, arene, and alkyl chain-bearing cyclic moieties. The results showed that the N-substituted benzimidazole derivatives bearing an alkyl chain and a nitrogen-containing 5- or 6-membered ring enhanced the cytotoxic effects on human breast adenocarcinoma (MCF-7) and human ovarian carcinoma (OVCAR-3) cell lines. Among the 24 synthesized compounds, (2E)-1-(1-(3-morpholinopropyl)-1H-benzimidazol-2 -yl)-3-phenyl-2-propen-1-one) (23a) reduced the proliferation of MCF-7 and OVCAR-3 cell lines demonstrating superior outcomes to those of cisplatin.

A series of new conjugated compounds with a –SCH₂– linkage were synthesized by chemical methods from imidazole and coumarin derivatives. The experimental results indicate that of the twenty newly synthesized imidazole–coumarin conjugates, three of them exhibited appealing EC₅₀ values (5.1–8.4 μM) and selective indices >20 against hepatitis C virus. Their potency and selectivity were increased substantially by modification of their structure with two factors: imidazole nucleus with a hydrogen atom at the N(1) position and coumarin nucleus with a substituent, such as Cl, F, Br, Me, and OMe. These guidelines provide valuable information for further development of conjugated compounds as anti-viral agents.

Hepatocellular carcinoma (HCC) is a common cause of cancer death worldwide. Sorafenib, a multikinase inhibitor, is the first-line drug approved by the Food and Drug Administration (FDA) for the treatment of patients with advanced HCC. However, most patients who continuously receive sorafenib may acquire resistance to this drug. Therefore, it is important to develop a new compound to treat liver cancer and sorafenib-resistant liver cancer. Barbituric acid derivatives have been used as antiasthmatic drugs in the clinic. We previously reported that a novel barbituric acid derivative inhibited carbon tetrachloride-induced liver fibrosis in mice, but its effects on liver cancer remain unknown. Thus, the purpose of this study was to investigate the antitumor effect of barbituric acid derivatives on HCC cells and sorafenib-resistant HCC cells (HCC-SRs). Our findings reveal that one of the barbituric acid derivatives, BA-5, significantly inhibited HCC and HCC-SR cell viability in a dose- and time-dependent manner. Therefore, compound BA-5 was selected for further experiments. Western blot data revealed that BA-5 treatment decreased the phosphorylation of AKT/p70s6k without affecting the MAPK pathway and increased cleaved PARP and cleaved caspase-7 in both HCC and HCC-SR cells. Since epithelial-mesenchymal transition plays a significant role in regulating cancer invasion and migration, we used the wound healing assay to evaluate the antimigratory effect of compound BA-5. The results showed that BA-5 treatment inhibited HCC and HCC-SR cell migration and reduced Vimentin protein expression. These results were confirmed by microarray analysis showing that BA-5 treatment influenced cancer cell motility and growth-related pathways. In the xenograft mouse model experiment, BA-5 administration significantly inhibited HCC cancer cell growth in mice. Furthermore, the combination of BA-5 with a low dose of regorafenib synergistically inhibited HCC-SR cell proliferation. In conclusion, our study showed that the barbituric acid derivative BA-5 is a new candidate for HCC and sorafenib-resistant HCC therapy.

This study aimed to develop a novel magnetic resonance imaging (MRI)-detectable boron (B)-containing nanoassemblies and evaluate their potential for boron neutron capture therapy (BNCT). Starting from the citrate-coated gold nanoparticles (AuNPs) (23.9 ± 10.2 nm), the diameter of poly (D, L-lactide-co-glycolide) AuNPs (PLGA-AuNPs) increased approximately 110 nm after the encapsulation of the PLGA polymer. Among various B drugs, the self-produced B cages had the highest loading efficiency. The average diameter of gadolinium (Gd)- and B-loaded NPs (PLGA-Gd/B-AuNPs) was 160.6 ± 50.6 nm with a B encapsulation efficiency of 28.7 ± 2.3%. In vitro MR images showed that the signal intensity of PLGA-Gd/B-AuNPs in T1-weighted images was proportional to its Gd concentration, and there exists a significantly positive relationship between Gd and B concentrations (R² = 0.74, p < 0.005). The hyperintensity of either 250 ± 50 mm³ (larger) or 100 ± 50 mm³ (smaller) N87 xenograft was clearly visualized at 1 h after intravenous injection of PLGA-Gd/B-AuNPs. However, PLGA-Gd/B-AuNPs stayed at the periphery of the larger xenograft while located near the center of the smaller one. The tumor-to-muscle ratios of B content, determined by inductively coupled plasma mass spectrometry, in smaller- and larger-sized tumors were 4.17 ± 1.42 and 1.99 ± 0.55, respectively. In summary, we successfully developed theranostic B- and Gd-containing AuNPs for BNCT in this study.