The inhibitory effects of novel prodrugs, inclusion complexes of 3‐(4′‐geranyloxy‐3′‐methoxyphenyl)‐2‐trans propenoic acid (GOFA) and auraptene (AUR) with β‐cyclodextrin (CD), on colon carcinogenesis were investigated using an azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Male CD‐1 (ICR) mice initiated with a single intraperitoneal injection of AOM (10 mg/kg body weight) were promoted by the addition of 1.5% (w/v) DSS to their drinking water for 7 days. They were then given a basal diet containing 2 dose levels (100 and 500 ppm) of GOFA/β‐CD or AUR/β‐CD for 15 weeks. At Week 18, the development of colonic adenocarcinoma was significantly inhibited by feeding with GOFA/β‐CD at dose levels of 100 ppm (63% reduction in multiplicity, p < 0.05) and 500 ppm (83% reduction in the multiplicity, p < 0.001), when compared with the AOM/DSS group (multiplicity: 3.36 ± 3.34). In addition, feeding with 100 and 500 ppm (p < 0.01) of AUR/β‐CD suppressed the development of colonic adenocarcinomas. The dietary administration with GOFA/β‐CD and AUR/β‐CD inhibited colonic inflammation and also modulated proliferation, apoptosis and the expression of several proinflammatory cytokines, such as nuclear factor‐kappaB, tumor necrosis factor‐α, Stat3, NF‐E2‐related factor 2, interleukin (IL)‐6 and IL‐1β, which were induced in the adenocarcinomas. Our findings indicate that GOFA/β‐CD and AUR/β‐CD, especially GOFA/β‐CD, are therefore able to inhibit colitis‐related colon carcinogenesis by modulating inflammation, proliferation and the expression of proinflammatory cytokines in mice.

Complexation between acyclovir (ACV), an antiviral drug used for the treatment of herpes simplex virus infection, and beta-cyclodextrin (beta-CD) was studied in solution and in solid states. Complexation in solution was evaluated using solubility studies and nuclear magnetic resonance spectroscopy (¹H-NMR). In the solid state, X-ray diffraction, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and dissolution studies were used. Solubility studies suggested the existence of a 1:1 complex between ACV and beta-CD. ¹H-NMR spectroscopy studies showed that the complex formed occurs with a stoichiometry ratio of 1:1. Powder X-ray diffraction indicated that ACV exists in a semicrystalline state in the complexed form with beta-CD. DSC studies showed the existence of a complex of ACV with beta-CD. The TGA studies confirmed the DSC results of the complex. Solubility of ACV in solid complexes was studied by the dissolution method and it was found to be much more soluble than the uncomplexed drug

The synthesis of novel Schiff's bases incorporating the five-membered 1,3,4-thiadiazole (series 7, 9) and 1,3,4-oxadiazole (series 8, 10) rings have been prepared and their liquid crystalline properties studied. All compounds of series 7 exhibit an enantiotropic smectic C phase. No liquid crystalline properties were observed for the compounds of series 8-10. A study of the structure/mesomorphic activity relationship is also described.

High-risk strains of human papillomavirus (HPV) have been identified as the etiologic agent of some anogenital tract, head, and neck cancers. Although prophylactic HPV vaccines have been approved; it is still necessary a drug-based treatment against the infection and its oncogenic effects. The E6 oncoprotein is one of the most studied therapeutic targets of HPV, it has been identified as a key factor in cell immortalization and tumor progression in HPV-positive cells. E6 can promote the degradation of p53, a tumor suppressor protein, through the interaction with the cellular ubiquitin ligase E6AP. Therefore, preventing the formation of the E6-E6AP complex is one of the main strategies to inhibit the viability and proliferation of infected cells. Herein, we propose an in silico pipeline to identify small-molecule inhibitors of the E6-E6AP interaction. Virtual screening was carried out by predicting the ADME properties of the molecules and performing ensemble-based docking simulations to E6 protein followed by binding free energy estimation through MM/PB(GB)SA methods. Finally, the top-three compounds were selected, and their stability in the E6 docked complex and their effect in the inhibition of the E6-E6AP interaction was corroborated by molecular dynamics simulation. Therefore, this pipeline and the identified molecules represent a new starting point in the development of anti-HPV drugs.