Asymmetric imidazole-4,5-dicarboxamide derivatives as SARS-CoV-2 main protease inhibitors: design, synthesis and biological evaluation.

The SARS-CoV-2 main protease, a vital enzyme for virus replication, is a potential target for developing drugs in COVID-19 treatment. Until now, three SARS-CoV-2 main protease inhibitors have been approved for COVID-19 treatment. This study explored the inhibitory potency of asymmetric imidazole-4,5-dicarboxamide derivatives against the SARS-CoV-2 main protease. Fourteen derivatives were designed based on the structure of the SARS-CoV-2 main protease active site, the hydrolysis mechanism, and the experience gained from the reported inhibitor structures. They were synthesized through a four-step procedure from benzimidazole and 2-methylbenzimidazole. SARS-CoV-2 main protease inhibition was evaluated in vitro by fluorogenic assay with lopinavir, ritonavir, and ebselen as positive references. N-(4-Chlorophenyl)-2-methyl-4-(morpholine-4-carbonyl)-1H-imidazole-5-carboxamide (5a2) exhibited the highest potency against the SARS-CoV-2 main protease with an IC50 of 4.79 ± 1.37 µM relative to ebselen with an IC50 of 0.04 ± 0.013 µM. Enzyme kinetic and molecular docking studies were carried out to clarify the inhibitory mechanism and to prove that the compound interacts at the active site. We also performed cytotoxicity assay to confirm that these compounds are not toxic to human cells.

Discovery of novel flavonoid derivatives as potential dual inhibitors against α-glucosidase and α-amylase: virtual screening, synthesis, and biological evaluation.

Diabetes mellitus is one of the top ten causes of death worldwide, accounting for 6.7 million deaths in 2021, and is one of the most rapidly growing global health emergencies of this century. Although several classes of therapeutic drugs have been invented and applied in clinical practice, diabetes continues to pose a serious and growing threat to public health and places a tremendous burden on those affected and their families. The strategy of reducing carbohydrate digestibility by inhibiting the activities of α-glucosidase and α-amylase is regarded as a promising preventative treatment for type 2 diabetes. In this study, we investigated the dual inhibitory effect against two polysaccharide hydrolytic enzymes of flavonoid derivatives from an in-house chemical database. By combining molecular docking and structure-activity relationship analysis, twelve compounds with docking energies less than or equal to - 8.0 kcal mol-1 and containing required structural features for dual inhibition of the two enzymes were identified and subjected to chemical synthesis and in vitro evaluation. The obtained results showed that five compounds exhibited dual inhibitory effects on the target enzymes with better IC50 values than the approved positive control acarbose. Molecular dynamics simulations were performed to elucidate the binding of these flavonoids to the enzymes. The predicted pharmacokinetic and toxicological properties suggest that these compounds are viable for further development as type 2 diabetes drugs.

Hepatitis B Birth Dose among Children in District 2 Hospital, Ho Chi Minh City, Vietnam: Prevalence and Associated Factors.

BACKGROUND: A birth dose of the hepatitis B vaccine will prevent most perinatally acquired infections and offers early protection from horizontal transmission. This article assessed the prevalence of the hepatitis B birth dose and associated factors among children in the District 2 Hospital. METHODS: A prospective cross-sectional study between June and December 2017 recruited parents/caregivers of children aged 12-59 months who were randomly selected at the vaccination department in the District 2 Hospital. The structured questionnaire applied was to collect the characteristics of participants and check the vaccination schedule. The birth dose was defined as the hepatitis B vaccine, which was given to children within 24 hours after birth. Additionally, a semistructured questionnaire was used for interviews and focus group discussions (FGDs) to assess the risk perceptions and barriers to vaccination. RESULTS: A total of 292 parents/caregivers had a mean age of 32.7 ± 6.8 years; among them, 88.7% were females. Their children had a mean age of 30.3 ± 13.9 months and 71.6% of these children received the hepatitis B birth dose, which correlated with the age of gestation (P < 0.05). In-depth interviews and FGDs found that most participants did not know that hepatitis B could be transmitted through childbirth, and barriers that affected the birth dose vaccine included children being sick, premature infants, or reason relating to physicians. CONCLUSIONS: The rate of hepatitis B birth dose was low, which resulted from associated factors such as premature birth, likely to be linked with false contraindications and beliefs that, potentially, the 2013 incident is still fresh in people's minds. Therefore, strategies to implement policies around the hepatitis B birth dose should be in line with current World Health Organization recommendations and strategies to modify current beliefs about vaccination.