Theoretical and experimental cocrystal screening of temozolomide with a series of phenolic acids, promising cocrystal coformers

The virtual cocrystal screening approach based on molecular electrostatic potential surface(MEPS)maps is a fast and feasible computational method to estimate the probability of cocrystal formation by calculating the difference in the interaction site pairing energies of monomers and that of their assemblies prior to experimental screening.In this paper,we report 12 cocrystal forms of temozolomide with mono-,di-,and trihydroxy benzoic acids,namely,3-hydroxy-,2,4-dihydroxy-,2,5-dihydroxy-,2,6-dihydroxy-,3,4-dihydroxy-,and 3,4,5-trihydroxy-benzoic acids,as well as benzoic acid,as pharmaceutical coformers for the first time.10 single crystals out of the 12 cocrystal forms were obtained and unequivocally determined by single-crystal X-ray diffraction,which clarified spatial arrangements,molecular conformations,and supramolecular synthons.MEPS further gains some insights into the sites of hydrogen bonding interactions for exploring combination patterns in these assemblies.Modulated stability of TMZ was successfully achieved by cocrystallization with these acids.

EETs mediate cardioprotection of salvianolic acids through MAPK signaling pathway

Salvianolic acids,including salvianolic acid A(SAA)and salvianolic acid B(SAB),are.the main water-soluble bioactive compounds isolated from the Chinese medicinal herb Danshen and have been shown to exert in vitro and in vivo cardiovascular protection.Recent studies suggest that epoxyeicosatrienoic acids(EETs),the primary cytochrome P4502J(CYP2J)epoxygenase metabolites of arachidonic acid,are involved in the progression of ischemic injury in diverse organs.Here,we investigated the relation between the protective effects of salvianolic acids and EETs/sEH as well as MAPK signaling pathway.In the present study,the rat acute myocardial infarction(AMI)model was established by the left anterior descending coronary artery occlusion.Our results showed that salvianolic acids significantly reduced ST-segment elevation and serum levels of CK-MB,LDH,and ALT in AMI rats,and significantly attenuated the caspase 3 expression and reduced the ratio of Bax/Bcl-2.ELISA measurement showed that salvianolic acids significantly increased the 14,15-EET levels in blood and heart,and attenuated hydrolase activity of sEH in heart of AMI rat.Western blotting analysis suggested that salvianolic acids significantly attenuated the phosphorylation of JNK and p38,and increased phosphorylation of ERK in heart.In conclusion,these results indicate that EETs/sEH and MAPK signaling pathways are important processes in cardioprotection of salvianolic acids.