Teaching the molecular aspects of drug–target interactions and selectivity is not always an easy task. In this context, the use of alternative and engaging approaches could help pharmacy and chemistry students better understand this important topic of medicinal chemistry. Herein a 4 h practical exercise that uses freely available software as a tool to teach the drug–target interaction process is described. This exercise is designed as a comparative approach based on the distinct cyclooxygenase 2 (COX2) affinities of ibuprofen and celecoxib. Students learn how to find crystallographic structures in free protein databases online and how to treat the raw crystallographic data. Thus, students learn how to analyze the drug arrangement on the active site, looking for areas that are related to the molecular recognition process. At the end of the class, students summarize all of the molecular requirements related to drug–target interactions and selectivity. Additionally, students visualize three-dimensionally the structure–activity relationship of ibuprofen and celecoxib.

Sulfonyl hydrazones were synthesized by one-pot reaction using sulfonyl chlorides, hydrazine hydrate and aldehydes under mild, cheap and environmental safe conditions. The optimized reaction afforded nine products with yields higher than 94% and four products with yields between 34% and 83%. Also, this paper reports, for the first time, the reduction of hydrazine amount (1.2 equiv) in sulfonyl hydrazones synthesis, presenting an excellent perspective to the sustainable production of new drug candidates.

high concentration can be an important risk factor for coronary diseases and atherosclerotic lesions. This lipid presents an endogenous biosynthesis that involves several steps; one of them is modulated by the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase). HMG-CoA reductase is inhibited by statins, such as simvastatin, in order to reduce seric become active. The structure of simvastatin has a lactone ring that undergoes enzymatic hydrolysis giving the 3,5-dihydroxy-heptanoate metabolite. This group is essential for simvastatin antilipemic activity, but significantly increases their water solubility. Make students understand the influence of chemical groups and organic functions on physicochemical properties and pharmacokinetic profiles of drugs, as simvastatin, is not an easy task. In this context, combine practical strategies and theoretical presentations of the concepts involved on drug biotransformation certainly could improve the teaching learning process. This manuscript correlates organic strategies and in silico techniques throught simvastatin hydrolysis followed by comparative ClogP measurement. This approach intends to allow students to have contact with a cross-platform and multidisciplinary learning, making it ludic, easier and more interesting than theoretical classes.Keywords: medicinal chemistry; simvastatin; prodrug; experimental class; antilipemics. INTRODUÇÃOAs lipoproteínas são necessárias para o transporte de lipídeos pelo plasma, sendo que os lipídeos mais comumente encontrados na corrente sanguínea são: o colesterol e seus ésteres, os triglicerídeos e os fosfolipídios.1 A concentração elevada de lipoproteínas complexadas a lipídeos no plasma constitui fator de risco importante para lesões ateroscleróticas e doenças coronarianas, sendo estas, o conjunto de doenças que mais geram vítimas fatais em todo o mundo. 2O colesterol consiste em um dos componentes de membranas celulares, além de ser um precursor essencial para a biossíntese de hormônios gonadotróficos (i.e. estradiol e testosterona), glicocorticóides (cortisol) e mineralocorticóides (aldosterona).3,4 Este pode ser obtido pelo indivíduo a partir de sua dieta, e também pode ser biossintetizado. A síntese endógena do colesterol é complexa e envolve diversas etapas, sendo uma das etapas iniciais, modulada pela enzima 3-hidroxi-3-metilglutaril coenzima A redutase (HMG-CoA redutase). Esta é fundamental à biossíntese do colesterol, originando o ácido mevalônico (Figura 1A), o qual dá prosseguimento à via catalítica, por redução da função tioéster do substrato endógeno (HMG-CoA). Dessa forma, ao inibir a HMG-CoA redutase, reduz-se a concentração de moléculas de colesterol sintetizadas pelo organismo. 5Os inibidores da HMG-CoA redutase, comumente conhecidos como estatinas, até o final da década de 2000 figuraram entre os medicamentos mais lucrativos utilizados na terapêutica, sendo prescritos com o intuito de reduzir os níveis séricos de colesterol.3,6 Estatinas são inibidoras competitivas da enzima HMG-CoA redutase...