New imidazole-2-thiones linked to acenaphythylenone as dual DNA intercalators and topoisomerase II inhibitors: structural optimization, docking, and apoptosis studies.

In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2H)-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that integrated key structural elements essential for DNA damage via direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles 5b and 5e in addition to 4-(4-chlorophenyl)imidazoles 5h and 5j would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds 5b and 5h against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than doxorubicin, respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors.

Postextubation Noninvasive Ventilation in Respiratory Distress Syndrome: A Randomized Controlled Trial.

OBJECTIVE: Successful extubation and prevention of reintubation remain primary goals in neonatal ventilation. Our aim was to compare three modalities of postextubation respiratory support-noninvasive positive pressure ventilation (NIPPV), nasal bilevel positive airway pressure (N-BiPAP), and nasal continuous positive airway pressure (NCPAP)-using the RAM cannula in preterm neonates with respiratory distress syndrome (RDS). Our secondary aim was to define the predictors of successful extubation. STUDY DESIGN: A total of 120 preterm neonates (gestational age ≤35 weeks) with RDS who had undergone primary invasive ventilation were randomized to receive either NIPPV, N-BiPAP, or NCPAP. The incidence of respiratory failure in the first 48 hours postextubation, total days of invasive and noninvasive ventilation, duration of hospitalization, and mortality were measured and compared among the three different noninvasive support modalities. RESULTS: There were no significant differences in the postextubation respiratory failure rates and the number of days of invasive as well as noninvasive ventilation among the three different support modalities (p > 0.05). The total number of days of mechanical ventilation and the duration of hospitalization were significantly higher in the N-BiPAP group than those in the NCPAP or NIPPV groups (p < 0.05). A gestational age of at least 29 weeks and a birth weight of at least 1.4 kg were predictive of successful extubation with a sensitivity of 98.2 and 85.3% and a specificity of 63.6 and 90.9%, respectively. CONCLUSION: Longer durations of mechanical ventilation and hospitalization were observed with N-BiPAP as a noninvasive mode of ventilation, but there was no significant difference in the extubation failure rates among the three modalities. Gestational age and birth weight were shown to be independent predictors of successful extubation of preterm neonates with RDS. KEY POINTS: · Successful extubation and reintubation prevention of preterms are primary goals in neonatal ventilation.. · NIPPV, N-BiPAP, and NCPAP could be used as postextubation noninvasive modes in preterm neonates.. · Gestational age and birth weight are independent predictors of successful extubation of preterms..