Molecular Modeling and Chemical Synthesis of New Safrol Oxime Ether Derivatives

Leishmaniasis, a neglected tropical disease with a high worldwide incidence, is considered a public health issue in Minas Gerais and Brazil, with a high degree of morbidity, not to mention the lack of therapeutic arsenal. The cysteine protease (rCPB2.8) and cyclin dependent kinase (CRK3), important enzymes for the parasite’s feasibility, were the targets chosen for investigation of the new drugs. The following study aimed to analyze several oximic derivatives starting from safrol, which can present an affinity profile for selected molecular targets using tools from molecular modeling and bioinformatics, planning and synthesis of brand new substances being tested for leishmanicidal drugs. The study allowed to verify that three oximic derivatives (5a, 5f and 5h) presented high affinity for the CRK3 enzyme, and that the compounds 5c and 5g presented good interaction by the amino acids of the catalytic site of the rCPB2.8 enzyme with atomic distances capable of generating covalent bonds, which are essential for enzyme inhibitory activity.

Urinary incontinence and diarrhoea associated with the switch from oral to injectable risperidone

ObjectiveUrgency, urinary incontinence and bowel disturbances are distressing side effects that have been observed during treatment with risperidone and other antipsychotics probably due to the receptor affinity profile. This occurrence can lead to poor compliance and therefore impair clinical outcome.MethodWe report the case of a 50 year‐old lady, who experienced urinary incontinence and diarrhoea, when switching from oral to injectable risperidone, which ceased when discontinuing the drug.Results and conclusionsIt should be taken into account that some side effects can be revealed when switching from oral to depot formulations due to non‐compliance to orals; nevertheless dose‐dependent mechanisms and individual metabolic variability must be considered when observing idiosyncratic reactions to drugs.