ABSTRACT
We report microwave synthesis of seven unique pyrimidine anchored derivatives (1-7) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1-7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1-7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC50 values of 89.24 ± 1.36 µM and 89.37 ± 1.17 µM, respectively. Molecular docking was performed for derivatives (1-7) on main protease for SARS-CoV-2 (PDB ID: 6LU7). Results revealed that most of the derivatives had superior or equivalent affinity for the 3CLpro, as determined by docking and binding energy scores. 6 topped the rest with highest binding energy score of -8.12 kcal/mol with inhibition constant reported as 1.11 µM. ADME, drug-likeness, and pharmacokinetics properties of 1-7 were tested using Swiss ADME tool. Toxicity analysis was done with pkCSM online server. All derivatives showed high GI absorption. Except 1 and 3, all derivatives showed blood brain barrier permeability. Most derivatives showed negative logKp values suggesting derivatives are less skin permeable and bioavailability score of all derivatives was 0.55. The toxicity analysis demonstrated that all derivatives have no skin sensitization properties. 6 and 7 showed maximum tolerated dose (Human) values of -0.03 and -0.018, respectively and absence of AMES toxicity.
ABSTRACT
We report microwave synthesis of seven unique pyrimidine anchored derivatives (1-7) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1-7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1-7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC50 values of 89.24±1.36 µM and 89.37±1.17 µM, respectively. Molecular docking was performed for derivatives (1-7) on main protease for SARS-CoV-2 (PDB ID: 6LU7). Results revealed that most of the derivatives had superior or equivalent affinity for the 3CLpro, as determined by docking and binding energy scores. 6 topped the rest with highest binding energy score of -8.12 kcal/mol with inhibition constant reported as 1.11 µM. ADME, drug-likeness, and pharmacokinetics properties of 1-7 were tested using Swiss ADME tool. Toxicity analysis was done with pkCSM online server. All derivatives showed high GI absorption. Except 1 and 3, all derivatives showed blood brain barrier permeability. Most derivatives showed negative logKp values suggesting derivatives are less skin permeable and bioavailability score of all derivatives was 0.55. The toxicity analysis demonstrated that all derivatives have no skin sensitization properties. 6 and 7 showed maximum tolerated dose (Human) values of -0.03 and -0.018, respectively and absence of AMES toxicity.
ABSTRACT
BACKGROUND: The outbreak of the coronavirus disease 2019 (COVID-19) pandemic was associated with the provision of multiple guidelines for the dental profession. All elective procedures were restricted, and only emergency procedures were performed. There was fear and anxiety among dentists while performing aerosol-generating procedures (AGPs), as they were considered to pose a high risk of COVID-19 transmission. OBJECTIVES: The aim of this study was to assess the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during AGPs, and to examine the association between risk severity and the number of AGPs performed per day. The efficacy of personal protective equipment (PPE) was also assessed. MATERIAL AND METHODS: This cross-sectional cohort study was based on an online questionnaire form completed by 629 general and specialized dentists between January 1 and February 28, 2021. The collected data referred to the sources of COVID-19 infection, the type of PPE used and the number of AGPs performed each day by dental healthcare professionals (DHCPs). For each question, the absolute numbers of responses as well as percentages were calculated. RESULTS: Among the 629 DHCPs, 113 (17.97%) contracted COVID-19. The risk of contracting COVID-19 during AGPs was the same as in the case of non-AGPs, and the infection risk was not associated with the number of AGPs performed per day. The efficacy of a surgical mask with a face shield/eye goggles was higher in comparison with all other types of PPE. Differences in the infection risk across the different types of PPE used were statistically significant (p < 0.001). CONCLUSIONS: The risk of COVID-19 transmission during AGPs is the same as in the case of non-AGPs. Thus, restrictions on the performance of elective AGPs should be lifted. On the other hand, the best protection during AGPs is provided by a surgical mask with a face shield/eye goggles.