Twelve novel quinazolinone–pyrimidine hybrids were synthesized, of which some of them showed dual functions as DPP-4 inhibitors and anti-cancer agents.

Fifteen derivatives of spirooxindole-4H-pyran (A 1 -A 15 ) were subjected to evaluate through intravenous infusion of pentylenetetrazole (PTZ) induced epilepsy mouse models. Four doses of the compounds (20, 40, 60, 80 mg/kg) were tested in comparison to diazepam as positive control. The resulted revealed that compounds A 3 and A 12 were the most active compounds and indicated signi cant anticonvulsant activity in the PTZ test. The tested compounds were prepared via a multicomponent reaction using graphene oxide (GO) based on the 1-(2-aminoethyl) piperazine as a novel heterogeneous organocatalyst. The prepared catalyst (GO-A.P.) was characterized using some diverse microscopic and spectroscopic procedures as well. The results showed high catalytic activity of the catalyst in the synthesis of spirooxindole-4H-pyran derivatives. The GO-A.P. catalyst was reusable at least for 5 times with no signi cant decrease in its catalytic action. In silico assessment of physico chemical activity of all compounds also were done which represented appropriate properties. Finally, molecular docking study was performed to achieve their binding a nities as γ-aminobutyric acid-A (GABA-A) receptor agonists as a plausible mechanism of their anticonvulsant action. Binding free energy values of the compounds represented strongly matched with biological activity.

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Thirteen novel isatin-ampyrone Schiff bases derivatives were synthesized in only two steps of 70%-90% overall yields. In vitro cytotoxic activity of these new Schiff bases against three human tumor cell lines (MCF-7, A549, and SCOV3) as well as normal breast cell line (MCF-10A) were evaluated by MTT assay. Structure-activity relationship of the tested compounds revealed that chlorine group at C-5 position of the isatin ring significantly increased the cytotoxic activity. This study generally led to introduce a highly active molecule (M 12 ) with IC 50 values of 5.12, 25.5, and 12.9 μΜ, on MCF-7, A549, and SCOV3, respectively. Furthermore, molecular docking studies of the synthesized compounds were also done to investigate their binding modes towards VEGFR-2 and JNK3-MAP kinase as the main targets for isatin-containing anticancer agents. Binding free energy values of the compounds showed positive correlation with their cytotoxic activities. To confirm the docking results, molecular docking simulations of potent compound (M 12 ) against VEGFR-2 and JNK3 MAP kinase were also performed. According to the cytotoxic results and in silico ADMET predictions together, M 12 can be considered as a potent candidate for the future anticancer studies.

OBJECT While malpractice litigation has had many negative impacts on health care delivery systems, information extracted from lawsuits could potentially guide toward venues to improve care. The authors present a comprehensive review of lawsuits within a tertiary academic neurosurgical department and report institutional and departmental strategies to mitigate liability by integrating risk management data with quality improvement initiatives. METHODS The Comprehensive Risk Intelligence Tool database was interrogated to extract claims/suits abstracts concerning neurosurgical cases that were closed from January 2008 to December 2012. Variables included demographics of the claimant, type of procedure performed (if any), claim description, insured information, case outcome, clinical summary, contributing factors and subfactors, amount incurred for indemnity and expenses, and independent expert opinion in regard to whether the standard of care was met. RESULTS During the study period, the Department of Neurosurgery received the most lawsuits of all surgical specialties (30 of 172), leading to a total incurred payment of $4,949,867. Of these lawsuits, 21 involved spinal pathologies and 9 cranial pathologies. The largest group of suits was from patients with challenging medical conditions who underwent uneventful surgeries and postoperative courses but filed lawsuits when they did not see the benefits for which they were hoping; 85% of these claims were withdrawn by the plaintiffs. The most commonly cited contributing factors included clinical judgment (20 of 30), technical skill (19 of 30), and communication (6 of 30). CONCLUSIONS While all medical and surgical subspecialties must deal with the issue of malpractice and liability, neurosurgery is most affected both in terms of the number of suits filed as well as monetary amounts awarded. To use the suits as learning tools for the faculty and residents and minimize the associated costs, quality initiatives addressing the most frequent contributing factors should be instituted in care redesign strategies, enabling strategic alignment of quality improvement and risk management efforts.

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Background: Azoles are the famous and widespread scaffold in the pharmaceutical industry through wide range of activities, high efficacy, and good tolerability and oral availability. Furthermore, azole derivatives have engrossed attentiveness as potent antimicrobial agents. Introduction: The purpose of this review is to execute an overview of the pharmacological aspects of the main scaffolds of azoles, including imidazole, benzimidazole, triazole and tetrazole which possessed antimicrobial activity from 2016 to 2020 as well as all of our publication in this field. In addition, we discussed the relationship between the structure and activity and molecular docking studies of the azole derivatives to provide key features and useful information for the synthesis of novel azole compounds with desirable biological activities. The presented structures in this review have been tested against several bacteria and fungi such that E. coli and C. albicans were common in all of these studies. Results: The comparison of reported MIC showed that fluconazole base structures were the most active ones as antifungal agents and triazole derivatives bearing nitrophenyl and coumarin moieties had the most antibacterial activity. Conclusion: Triazole and imidazole scaffolds are more important in the design of antimicrobial compounds than other azole derivatives like benzimidazole or tetrazole. All the most active compounds fulfilled the Lipinski rules.