Computationally designed prodrugs of statins based on Kirby’s enzyme model

DFT calculations at B3LYP/6-31G(d,p) for intramolecular proton transfer in Kirby’s enzyme models 1–7 demonstrated that the reaction rate is dependent on the distance between the two reacting centers, r_GM, and the hydrogen bonding angle, α, and the rate of the reaction is linearly correlated with r_GM and α. Based on these calculation results three simvastatin prodrugs were designed with the potential to provide simvastatin with higher bioavailability. For example, based on the calculated log EM for the three proposed prodrugs, the interconversion of simvastatin prodrug ProD 3 to simvastatin is predicted to be about 10 times faster than that of either simvastatin prodrug ProD 1 or simvastatin ProD 2. Hence, the rate by which the prodrug releases the statin drug can be determined according to the structural features of the promoiety (Kirby’s enzyme model).

Crowding does not affect monarch butterflies’ resistance to a protozoan parasite

Host density is an important factor when it comes to parasite transmission and host resistance. Increased host density can increase contact rate between individuals and thus parasite transmission. Host density can also cause physiological changes in the host, which can affect host resistance. Yet, the direction in which host density affects host resistance remains unresolved. It is also unclear whether food limitation plays a role in this effect. We investigated the effect of larval density in monarch butterflies, Danaus plexippus, on the resistance to their natural protozoan parasite Ophryocystis elektroscirrha under both unlimited and limited food conditions. We exposed monarchs to various density treatments as larvae to mimic high densities observed in sedentary populations. Data on infection and parasite spore load were collected as well as development time, survival, wing size, and melanization. Disease susceptibility under either food condition or across density treatments was similar. However, we found high larval density impacted development time, adult survival, and wing morphology when food was limited. This study aids our understanding of the dynamics of environmental parasite transmission in monarch populations, which can help explain the increased prevalence of parasites in sedentary monarch populations compared to migratory populations.