Sesquiterpene Lactones with Anti-Hepatitis C Virus Activity Using Molecular Descriptors

Hepatitis C is a worldwide public health problem. The available therapies are limited by their partial effectiveness and with meaningful side-effects. Sesquiterpene lactones (SLs) are a group of natural products with a wide variety of chemical structures and biological activities associated. There are few studies about the influence of the molecular structure of SLs for the anti-hepatitis C virus activity. In the present work, SLs are investigated in a subgenomic RNA replicon assay system and were analyzed using multiple linear regression along with self-organizing maps with DRAGON descriptors in order to identify the structural requirements for their biological activity and to predict the inhibitory potency of SLs. Characteristics such as stereochemistry and electronic effects demonstrated to be important for their anti-HCV activity, and the SOM produced a clear separation betwenn active and inactive compounds. Therefore, it is possible to use this map as a filter for virtual screening to predict the anti-HCV activity of SLs.

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of kappa group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female reproduction