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1.
Eur Rev Med Pharmacol Sci ; 27(15): 6972-6984, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37606107

RESUMO

OBJECTIVE: Decreased expression of the mitochondrial protein frataxin is the cause of the neurodegenerative disorder Friedreich's ataxia. In patients with cardiac disorders, the death rate of this disease is very high, up to 66%. In order to combat Friedreich ataxia, which is a potentially toxic disorder, de novo drug discovery and design have been created utilizing the approach of compound engineering with halogens. This study aimed to investigate the potential for effective treatment of Friedreich ataxia. MATERIALS AND METHODS: The screening of twenty different agonist compounds was carried out in order to find the most promising agonist compound that may be used for molecular docking prediction against the Frataxin Protein. The compound with the lowest binding energies is then optimized by halogens. The final candidate's drug-like properties are identified through Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling. Lipinski's rule of five was checked. Molecular dynamic stimulations were evaluated. RESULTS: The most potent agonist compound was identified out of twenty different compounds utilizing a docking approach against the Frataxin Protein. The compound with the lowest binding energies was next subjected to optimization by halogens. The optimized agonist 9-[1-[(1S, 5R)-8, 8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl]triazol-4-yl]fluoren-9-ol  has higher binding energy of -10.4Kcal/mol with molecular weight of 705.63 g/mol. Drug-like properties are identified through ADMET profiling, having water solubility of about -7.59, skin permeation -7.08 cm/s, bioavailability score 0.17, and high GI absorption. The candidate fulfills the Lipinski rule of five and portrays efficient molecular dynamic stimulations. CONCLUSIONS: The selected agonist is one of the most potent compounds in increasing Frataxin protein expression. Furthermore, optimization with halogens can be a productive approach to improve the candidate's drug efficacy. The development of effective medications for the treatment of Friedreich ataxia would be aided by the results of these computational investigations.


Assuntos
Ataxia de Friedreich , Humanos , Ataxia de Friedreich/tratamento farmacológico , Ataxia de Friedreich/genética , Halogênios , Simulação de Acoplamento Molecular , Proteínas de Ligação ao Ferro/genética , Frataxina
2.
Eur Rev Med Pharmacol Sci ; 27(1): 20-25, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36647848

RESUMO

OBJECTIVE: Osteoporosis is a bone disease that develops when bone mineral density and bone mass decrease, or when the quality of bone changes. It is the most common bone disease, representing a major public health problem. This study aimed to assess the knowledge of risk factors for osteoporosis among adults above 40 in the Qassim region, Saudi Arabia. SUBJECTS AND METHODS: This is a cross-sectional study conducted among adults who were above 40 years of age and living in the Qassim region, Saudi Arabia. A survey questionnaire was distributed to respondents while they attended primary health care as well as online via social media. RESULTS: 390 participants responded to our survey (65.6% females vs. 34.4% males). The most common age group was 41 to 50 years (59.7%). The prevalence of participants who were having information about osteoporosis was 59%. Overall, the knowledge of participants about osteoporosis was good (63.1%), 33.3% had moderate knowledge and only 3.6% were assumed to have a poor knowledge level. Factors associated with increased knowledge was being a female and being an employee. CONCLUSIONS: Although the knowledge of the adult population aged above 40 years old seems adequate, there is still room for improvement. Female participants who were currently employed demonstrated a better understanding of osteoporosis than other adults. Further research is warranted to establish the effect of advanced age on their level of understanding regarding osteoporosis and its risk factors.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Osteoporose , Masculino , Adulto , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Arábia Saudita/epidemiologia , Estudos Transversais , Osteoporose/epidemiologia , Fatores de Risco
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