No abstract

Background and Objectives: Drug design strategies to develop novel broad-spectrum antibacterial agents for the treatment of respiratory tract infections that can combat bacterial resistance are currently gaining momentum. 2,4- thiazolidinedione is a structural scaffold that contains pharmacophores similar to β-lactam and non- β-lactam antibiotics. The objective of the study was to synthesize newer 3,5-disubstituted-2,4-thiazolidinediones (DTZDs) and subject them to in-vitro antibacterial screening against bacterial pathogens. Also, we performed in-silico docking of selected compounds to penicillin-binding proteins and beta-lactamases. Methods: Intermediate Schiff bases were prepared by reaction between 2,4-thiazolidinedione and an appropriate aldehyde followed by acylation of the ring nitrogen with 3-brompropanoyl chloride resulting in DTZDs. Minimum inhibitory concentrations were determined against few bacteria infecting the respiratory tract by the broth tube dilution method. Zones of inhibitions against the bacteria were also determined using agar well diffusion technique. Molecular docking of the compounds to all types of penicillin-binding proteins (PBPs) and β-lactamases was also carried out. Results: Compounds DTZD12 and DTZD16 exhibited broad-spectrum antibacterial activity. The minimum inhibitory concentrations of the compounds were 175μg/100μL. Measurements of the zones of inhibitions indicated that compound DTZD12 was more active than DZTD16. E. Coli was the most susceptible organism. Docking results established that both the compounds were able to interact with PBPs and β-lactamases through strong hydrogen bonds, especially the unique interaction with active serine residue of the PBP for inhibition of cell wall synthesis. Conclusion: DTZD12 and DTZD16 can be developed into antibacterial drugs for respiratory tract infections to oppose bacterial resistance, or can also be used as leads for repurposing the existing 2,4-thiazolidinediones.

Objectives; to evaluate the quality of life among patients with chronic rhino sinusitis and the risk of developing depression. Design; An observation cross section study. Setting; the quality of life was assessed using 2-item sinonasal outcome test (SNOT-22) while Patient Health Questionnaire-2 (PHQ-2) used for screen of depression and Stress was analyzed using the Kessler Psychological Distress Scale (10 items representing five psychological distress traits were assessed with a five-point scale) Participants; 1072 patients with chronic rhino sinusitis. Main outcome measures; Influence of Chronic Rhino sinusitis on Quality of Life and Risk of Depression and Lost Productivity. Results; the level of quality of life affection was moderate in 159 (24.77%) and severe in 483 (75.23%) of participants with CRS. The mean score of PHQ-2 for assessing the risk of major depression was 4.17 + 1.74 in participants with CRS. 135 (21.03%) were normal (not at risk of major depression) and 507 (78.97%) were at risk of major depression. According to the Kessler Psychological Distress Scale: 759 patients (70.8%) were positive with a mean total perceived stress score of 16.92 ± 7.34, whereas 313(29.2%) were negative with a mean total perceived stress score of 6.08 ± 2.7. The difference was statistically significant Conclusions; Patients with CRS are at risk of depression, poor quality of life and bad work performance. Despite the supportive treatment that used to provide to such patients, a clinical comprehensive approach should be considered to relief the impact on patients’ quality of life.