[1,2,4]triazolo[4,3-a]quinoxaline as Novel Scaffold in the Imiqualines Family: Candidates with Cytotoxic Activities on Melanoma Cell Lines.

Cutaneous melanoma is one of the most aggressive human cancers and is the deadliest form of skin cancer, essentially due to metastases. Novel therapies are always required, since cutaneous melanoma develop resistance to oncogenic pathway inhibition treatment. The Imiqualine family is composed of heterocycles diversely substituted around imidazo[1,2-a]quinoxaline, imidazo[1,2-a]pyrazine, imidazo[1,5-a]quinoxaline, and pyrazolo[1,5-a]quinoxaline scaffolds, which display interesting activities on a panel of cancer cell lines, especially melanoma cell lines. We have designed and prepared novel compounds based on the [1,2,4]triazolo[4,3-a]quinoxaline scaffold through a common synthetic route, using 1-chloro-2-hydrazinoquinoxaline and an appropriate aldehyde. Cyclization is ensured by an oxidation-reduction mechanism using chloranil. The substituents on positions 1 and 8 were chosen based on previous structure-activity relationship (SAR) studies conducted within our heterocyclic Imiqualine family. Physicochemical parameters of all compounds have also been predicted. A375 melanoma cell line viability has been evaluated for 16 compounds. Among them, three novel [1,2,4]triazolo[4,3-a]quinoxalines display cytotoxic activities. Compounds 16a and 16b demonstrate relative activities in the micromolar range (respectively, 3158 nM and 3527 nM). Compound 17a shows the best EC50 of the novel series (365 nM), even if EAPB02303 remains the lead of the entire Imiqualine family (3 nM).

How social inequalities impact the course of treatment and care for patients with type 2 diabetes mellitus: study protocol for a qualitative cross-sectional study from the patient's perspective.

INTRODUCTION: Studies from various scientific disciplines have demonstrated that socioeconomic inequalities in type 2 diabetes mellitus negatively affect groups with a low socioeconomic status. Furthermore, socioeconomic inequalities also exist in terms of access to, and utilisation and perceived quality of, diabetological care. The aim of this qualitative study, which focuses on the patient's perspective, is to provide insights into the ways socioeconomic inequalities impact the course of treatment and care of patients with type 2 diabetes mellitus. The study aims to develop an understanding of how socioeconomic inequalities in care arise. METHODS AND ANALYSIS: A cross-sectional qualitative study will be conducted using a sample of about 20 patients with type 2 diabetes mellitus aged 18 and older. Patients will be recruited successively from the University Hospital in Halle/Saale, Germany, a general practitioner's office, and in a specialised diabetological practice. The patients will be interviewed personally once, using semistructured qualitative interviews. All interviews will be recorded, transcribed, and analysed based on Grounded Theory. ETHICS AND DISSEMINATION: All interviewees will receive comprehensive written information about the study and sign a declaration of consent prior to the interview. The study will comply rigorously with data protection legislation. The research team has obtained the approval of the Ethical Review Committee at the MLU Halle-Wittenberg, Germany. The results of the study will be published in high-quality, peer-reviewed international journals, presented at several congresses and used for developing follow-up research projects. TRIAL REGISTRATION NUMBER: This study has been registered with the German Clinical Trials Register and assigned DRKS00007847.