Synthesis, structure elucidation, Hirshfeld surface analysis, DFT, and molecular docking of new 6-bromo-imidazo[4,5-b]pyridine derivatives as potential tyrosyl-tRNA synthetase inhibitors.

Novel 6-bromo-imidazo[4,5-b]pyridine derivatives (2-4, 5a-13a, and 6b, 8b-13b) have been synthesized based on a developed systematic approach involving the condensation of 5-Bromo-2,3-diaminopyridine with a suitable aromatic aldehyde in the presence of molecular iodine in water, followed by alkylation reactions using different alkyl dibromide agents. The synthesized compounds were characterized by the NMR spectroscopy technique. The structures of 8a, 9a, 12a, and 11b were confirmed using monocrystalline X-ray crystallography. Theoretical calculations have been carried out using DFT and TD-DFT methods at the B3LYP/6-31G++(d,p) level of theory. Intermolecular contacts between units of 8a, 9a, 12a, and 11b were determined through the Hirshfeld surface analysis. The molecular docking study has been performed to determine the binding affinity of 8a, 9a, 12a, and 11b into the binding site of S. aureus tyrosyl-tRNA synthetase as a target enzyme, and the results revealed that 9a is the most potent compound among the selected compounds with a binding affinity of -8.74 Kcal/mol.Communicated by Ramaswamy H. Sarma.

The influence of wearing a mask on the projected first impressions and attractiveness levels of smiling individuals.

OBJECTIVE: To evaluate the effect of mask wearing on facial attractiveness and projected first impressions during the COVID-19 pandemic. METHODS: A total of eight models were evaluated by 200 live raters and 750 online raters both with and without masks while smiling maximally. Both live and online raters looked at the models for 15 s, then completed a first impressions questionnaire. RESULTS: Overall ratings for attractiveness were higher for both masked and unmasked conditions in-person versus online. Males were perceived more favorably both in impressions and attractiveness online when masked, whereas in person they were more favorable when unmasked. Females were perceived more favorably in impressions when unmasked both online and in person, but their attractiveness rating was higher when masked both online and in person. Regardless of gender and masking state, all first impressions were more favorable in person versus online. The differences were statistically significant (all p < 0.05). CONCLUSIONS: Face masks have different effects for males versus females in both an online and in-person setting. Men are perceived more positively in-person when they smile unmasked while they are better ranked online when they smile masked. Females are better perceived in all domains other than attractiveness when smiling unmasked both online and in person. To optimize first impressions, individuals should seek to meet in person whenever possible when forming new relationships.

Crystal structure, Hirshfeld surface analysis and DFT study of 6-bromo-3-(5-bromo-hex-yl)-2-[4-(di-methyl-amino)-phen-yl]-3H-imidazo[4,5-b]pyridine.

In the title mol-ecule, C20H24Br2N4, the imidazo-pyridine moiety is not planar as indicated by the dihedral angle of 2.0 (2)° between the constituent rings; the 4-di-methyl-amino-phenyl ring is inclined to the mean plane of the imidazole ring by 27.4 (1)°. In the crystal, two sets of C-H⋯π(ring) inter-actions form stacks of mol-ecules extending parallel to the a-axis direction. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯H (42.2%), H⋯C/C⋯H (23.1%) and H⋯Br/Br⋯H (22.3%) inter-actions. The optimized structure calculated using density functional theory (DFT) at the B3LYP/ 6-311 G(d,p) level is compared with the experimentally determined structure in the solid state. The calculated HOMO-LUMO energy gap is 2.3591 eV.

Crystal structure, Hirshfeld surface analysis and DFT studies of 6-bromo-3-(12-bromo-dodec-yl)-2-(4-nitro-phen-yl)-4H-imidazo[4,5-b]pyridine.

The title compound, C24H30Br2N4O2, consists of a 2-(4-nitro-phen-yl)-4H-imidazo[4,5-b]pyridine entity with a 12-bromo-dodecyl substituent attached to the pyridine N atom. The middle eight-carbon portion of the side chain is planar to within 0.09 (1) Šand makes a dihedral angle of 21.9 (8)° with the mean plane of the imidazolo-pyridine moiety, giving the mol-ecule a V-shape. In the crystal, the imidazolo-pyridine units are associated through slipped π-π stacking inter-actions together with weak C-HPyr⋯ONtr and C-HBrmdc-yl⋯ONtr (Pyr = pyridine, Ntr = nitro and Brmdcyl = bromo-dodec-yl) hydrogen bonds. The 12-bromo-dodecyl chains overlap with each other between the stacks. The terminal -CH2Br group of the side chain shows disorder over two resolved sites in a 0.902 (3):0.098 (3) ratio. Hirshfeld surface analysis indicates that the most important contributions for the crystal packing are from H⋯H (48.1%), H⋯Br/Br⋯H (15.0%) and H⋯O/O⋯H (12.8%) inter-actions. The optimized mol-ecular structure, using density functional theory at the B3LYP/ 6-311 G(d,p) level, is compared with the experimentally determined structure in the solid state. The HOMO-LUMO behaviour was elucidated to determine the energy gap.

Trends and Outcomes of Non-Small-Cell Lung Cancer in Omani Patients: Experience at a university hospital.

OBJECTIVES: The incidence of lung cancer in Oman has shown a gradual but definitive increase since 2002. This study aimed to evaluate the demographic and epidemiological characteristics and survival outcomes of patients with non-small-cell lung cancer (NSCLC) at a university hospital in Oman. METHODS: This study was conducted from January to June 2016. A retrospective analysis was performed of consecutive patients diagnosed with NSCLC presenting to the Sultan Qaboos University Hospital (SQUH) in Muscat, Oman, between March 2000 and December 2015. Clinical features at presentation and prognostic and predictive markers were reviewed. Kaplan-Meir estimates were used to determine relapse-free survival, progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 104 patients presented to SQUH during the study period. The median age at diagnosis was 64 years. Overall, 62 patients (59.6%) had adenocarcinomas. Only 12 patients (11.5%) presented in the early stages (I or II) of the disease and the majority of patients had an Eastern Cooperative Oncology Group performance status of 1 (27.9%) or 2 (26.0%). The prevalence of epidermal growth factor receptor mutations was 27.9%. The median PFS for patients with advanced disease (stages III or IV) was five months and the median OS for all patients was seven months. After five years, 50.0%, 60.0%, 10.0% and 8.0% of patients with disease stages I, II, III and IV, respectively, were alive. CONCLUSION: Patients with NSCLC in Oman were found to present at an advanced stage. However, patient outcomes were similar to those reported in the USA.