Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

W.H.O. predicts that there will be some 438 million diabetic patients in 2030, most of them living in developing countries. The IFD estimates that the prevalence of diabetes will rise by 98% in Africa during the next 20 years, with dramatic implications for public health and national budgets of the poorest countries. Type 2 diabetes is the most common form in Africa; type 1 is rarer than in western countries and tends to occur later. Two other forms seem specific to black Africans: ketosis-prone atypical diabetes, and tropical malnutrition-related diabetes. An increasing prevalence of obesity, diabetes and impaired glucose tolerance is observed in all parts of Africa. Several factors contribute to this situation, including aging, dietary transitions and lack of physical activity, all of which are related to rapid urbanization. In Africa, diabetes is associated with a high mortality rate, especially among insulin-dependent patients. Poor metabolic control can lead to severe ketosis and hypoglycemic accidents that carry a poor prognosis. Microvascular complications include retinopathy and nephropathy, and most patients cannot afford hemodialysis. Foot ulcers are frequent, due to trauma and neuropathies. Macrovascular complications are also increasing, with a high prevalence of hypertension. The poor prognosis of diabetes in Africa is related to late diagnosis, poor education, inadequate access to insulin, antidiabetic drugs and glycemia self-monitoring devices, absence of controlled diets, and difficult access to medical care in rural areas. Patient empowerment, knowledge and self-care must be improved. African governments must develop national prevention programs. Special attention must be paid to the prevention of obesity and diabetes. The urban environment, infrastructure, education, exercise and safe nutrition must be part of an overall policy designed to reduce the burden of chronic non transmissible diseases.
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PMID:[The burden of diabetes in Africa: a major public health problem]. 2253 May 17

Angiotensin II receptor type 1 (AT1) antagonists are the most recent drug class against hypertension. Recently first crystal structure of AT1 receptor is deposited to the protein data bank (PDB ID: 4YAY). In this work, several molecular screening methods such as molecular docking and de novo design studies were performed and it is found that oxazolone and imidazolone derivatives reveal similar/better interaction energy profiles compared to the FDA approved sartan molecules at the binding site of the AT1 receptor. A database consisting of 3500-fragments were used to enumerate de novo designed imidazolone and oxazolone derivatives and hereby more than 50000 novel small molecules were generated. These derivatives were then used in high throughput virtual screening simulations (Glide/HTVS) to find potent hit molecules. In addition, virtual screening of around 18 million small drug-like compounds from ZINC database were screened at the binding pocket of the AT1 receptor via Glide/HTVS method. Filtered structures were then used in more sophisticated molecular docking simulations protocols (i.e., Glide/SP; Glide/XP; Glide/IFD; Glide/QPLD, and GOLD). However, the K+ ion channel/drug interactions should also be considered in studies implemented in molecular level against their cardiovascular risks. Thus, selected compounds with high docking scores via all diverse docking algorithms are also screened at the pore domain regions of human ether-a-go-go-related gene (hERG1) K+ channel to remove the high affinity hERG1 blocking compounds. High docking scored compounds at the AT1 with low hERG1 affinity is considered for long molecular dynamics (MD) simulations. Post-processing analysis of MD simulations assisted for better understanding of molecular mechanism of studied compounds at the binding cavity of AT1 receptor. Results of this study can be useful for designing of novel and safe AT1 inhibitors.
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PMID:Structure-based design of hERG-neutral antihypertensive oxazalone and imidazolone derivatives. 2895 53

Angiotensin II receptor type 1 (AT1) antagonists are the most recent drug class against hypertension. Recently first crystal structure of AT1 receptor is deposited to the protein data bank (PDB ID: 4YAY). In this work, several molecular screening methods such as molecular docking and de novo design studies were performed and it is found that oxazolone and imidazolone derivatives reveal similar/better interaction energy profiles compared to the FDA approved sartan molecules at the binding site of the AT1 receptor. A database consisting of 3500-fragments were used to enumerate de novo designed imidazolone and oxazolone derivatives and hereby more than 50000 novel small molecules were generated. These derivatives were then used in high throughput virtual screening simulations (Glide/HTVS) to find potent hit molecules. In addition, virtual screening of around 18 million small drug-like compounds from ZINC database were screened at the binding pocket of the AT1 receptor via Glide/HTVS method. Filtered structures were then used in more sophisticated molecular docking simulations protocols (i.e., Glide/SP; Glide/XP; Glide/IFD; Glide/QPLD, and GOLD). However, the K+ ion channel/drug interactions should also be considered in studies implemented in molecular level against their cardiovascular risks. Thus, selected compounds with high docking scores via all diverse docking algorithms are also screened at the pore domain regions of human ether-a-go-go-related gene (hERG1) K+ channel to remove the high affinity hERG1 blocking compounds. High docking scored compounds at the AT1 with low hERG1 affinity is considered for long molecular dynamics (MD) simulations. Post-processing analysis of MD simulations assisted for better understanding of molecular mechanism of studied compounds at the binding cavity of AT1 receptor. Results of this study can be useful for designing of novel and safe AT1 inhibitors.
 ...
PMID:Structure-based design of hERG-neutral antihypertensive oxazalone and imidazolone derivatives. 2915 80