Identification of potential inhibitors for N-myristoyltransferase (NMT) protein of Plasmodium vivax.

Malaria is a neglected parasitic infection of global importance. It is mainly present in tropical countries and caused by a protozoa that belongs to the genus Plasmodium. The disease vectors are female Anopheles mosquitoes infected with the Plasmodium spp. According to the World Health Organization (WHO), there were 241 million malaria cases worldwide in 2020 and approximately 627 thousand malaria deaths in the same year. The increasing resistance to treatment has been a major problem since the beginning of the 21st century. New studies have been conducted to find possible drugs that can be used for the eradication of the disease. In this scenario, a protein named N-myristoyltransferase (NMT) has been studied as a potential drug target. NMT has an important role on the myristoylation of proteins and binds to the plasma membrane, contributing to the stabilization of protein-protein interactions. Thus, inhibition of NMT can lead to death of the parasite cell. Therefore, in order to predict and detect potential inhibitors against Plasmodium NMT, Computer-Aided Drug Design techniques were used in this research that involve virtual screening, molecular docking, and molecular dynamics. Three potential compounds similar to a benzofuran inhibitor were identified as stable PvNMT ligands. These compounds (EXP90, ZBC205 and ZDD968) originate from three different sources, respectively: a commercial library, a natural product library, and the FDA approved drugs dataset. These compounds may be further tested in in vitro and in vivo inhibition tests against Plasmodium vivax NMT.Communicated by Ramaswamy H. Sarma.

Peripheral arterial occlusive disease and ankle-brachial index in patients who had coronary angiography.

OBJECTIVE: To evaluate the prevalence of peripheral arterial disease (PAD) in patients with coronary arterial disease. To evaluate the relation between ankle-brachial index (ABI) and coronary arterial disease, and its correlation with cardiovascular risk factors. METHOD: ABI investigated with Doppler ultrasonic device. Clinical characteristics researched: age, gender, diabetes, hypertension, alcoholism, smoking and obesity. POPULATION: 113 patients who had coronary angiography. First analyses: 2 groups - absence and presence of coronary arterial disease. Second analyses: 3 groups - Group 1 - absence of coronary lesion; Group 2 - stenosis <70%; and Group 3 - stenosis >70%. Third analyses: 2 groups - absence and presence of PAD. RESULTS: 90.76% of patients with coronary arterial disease presented PAD. There were significant difference including age (p<0.001), hypertension (p<0.001). smoking (p<0.001), body mass index (BMI) (p<0.001), systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (DBP) (p<0.001) and pulse pressure (PP) (p<0.001) and ABI (p<0.001) between patients with and without coronary lesion. There were significant difference including age (p<0.001), diabetes (p=0.030), hypertension (p<0.001), smoking (p<0.001), BMI (p<0.001), SBP (p<0.001), DBP (p<0.001) and PP (p<0.001) and ABI (p<0.001) between patients divided as severity of coronary arterial disease. There were significant difference including age (p<0.001), hypertension (p<0.001), smoking (p<0.001), BMI (p<0.001), SBP (p<0.001), DBP (p<0.001) and PP (p<0.001) between patients with and without PAD. By Logistic Regression Analysis, old obese patients with ABI<0.90 have a risk of coronary lesion of 98.93%. CONCLUSION: ITB<0.90 might be a marker of coronary arterial disease in patients at risk of cardiovascular diseases.

Doença arterial obstrutiva periférica e índice tornozelo-braço em pacientes submetidos à angiografia coronariana / Peripheral arterial occlusive disease and ankle-brachial index in patients who had coronary angiography

OBJETIVO: Avaliar a prevalência de doença arterial obstrutiva periférica (DAOP) em coronariopatas. Avaliar a relação entre índice Tornozelo-Braço (ITB) e doença coronariana, e sua correlação com fatores de risco cardiovascular. MÉTODO: ITB investigado com ultra-sonografia Doppler. Características clínicas pesquisadas: idade, sexo, diabetes mellitus, hipertensão arterial sistêmica, etilismo, tabagismo e obesidade. População: 113 pacientes submetidos à angiografia coronariana. Primeira análise: 2 grupos - ausência e presença de coronariopatia. Segunda análise: 3 grupos - Grupo 1 - ausência de lesão coronariana; Grupo 2 - estenose < 70 por cento; e Grupo 3 - estenose > 70 por cento. Terceira análise: 2 grupos - ausência e presença de DAOP. RESULTADOS: 90,76 por cento dos coronariopatas apresentaram DAOP. Houve diferença significante quanto à faixa etária (p<0,001), hipertensão (p<0,001), tabagismo (p<0,001), IMC (p<0,001), pressão sistólica (p<0,001), diastólica (p<0,001) e de pulso (p<0,001) e ITB (p<0,001) entre indivíduos com e sem lesão coronariana. Houve diferença significante quanto à faixa etária (p<0,001), diabetes (p=0,030), hipertensão (p<0,001), tabagismo (p<0,001), IMC (p<0,001), pressão sistólica (p<0,001), diastólica (p<0,001) e de pulso (p<0,001) e ITB (p<0,001) entre os pacientes divididos quanto ao grau da coronariopatia. Houve diferença significante quanto à faixa etária (p<0,001), hipertensão (p<0,001), tabagismo (p<0,001), IMC (p<0,001), pressão sistólica (p<0,001), diastólica (p<0,001) e de pulso (p<0,001) entre pacientes com e sem DAOP. Pela Análise de Regressão Logística, pacientes idosos, obesos e com ITB < 0,90 apresentam probabilidade de lesão coronariana de 98,93 por cento. CONCLUSÃO: ITB < 0,90 constitui um possível marcador de doença arterial coronariana em pacientes com risco de doenças cardiovasculares.

OBJECTIVE: To evaluate the prevalence of peripheral arterial disease (PAD) in patients with coronary arterial disease. To evaluate the relation between ankle-brachial index (ABI) and coronary arterial disease, and its correlation with cardiovascular risk factors. METHOD: ABI investigated with Doppler ultrasonic device. Clinical characteristics researched: age, gender, diabetes, hypertension, alcoholism, smoking and obesity. Population: 113 patients who had coronary angiography. First analyses: 2 groups - absence and presence of coronary arterial disease. Second analyses: 3 groups - Group 1 - absence of coronary lesion; Group 2 - stenosis <70 percent; and Group 3 - stenosis >70 percent. Third analyses: 2 groups - absence and presence of PAD. RESULTS: 90.76 percent of patients with coronary arterial disease presented PAD. There were significant difference including age (p<0.001), hypertension (p<0.001). smoking (p<0.001), body mass index (BMI) (p<0.001), systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (DBP) (p<0.001) and pulse pressure (PP) (p<0.001) and ABI (p<0.001) between patients with and without coronary lesion. There were significant difference including age (p<0.001), diabetes (p=0.030), hypertension (p<0.001), smoking (p<0.001), BMI (p<0.001), SBP (p<0.001), DBP (p<0.001) and PP (p<0.001) and ABI (p<0.001) between patients divided as severity of coronary arterial disease. There were significant difference including age (p<0.001), hypertension (p<0.001), smoking (p<0.001), BMI (p<0.001), SBP (p<0.001), DBP (p<0.001) and PP (p<0.001) between patients with and without PAD. By Logistic Regression Analysis, old obese patients with ABI<0.90 have a risk of coronary lesion of 98.93 percent. CONCLUSION: ITB<0.90 might be a marker of coronary arterial disease in patients at risk of cardiovascular diseases.