[From the practice of monitoring SARS-CoV-2 test sites in the city of Cologne]. / Aus der Praxis der Überwachung der SARS-CoV-2-Teststellen im Stadtgebiet Köln.

In spring 2021, a law for the nationwide opening of test centers in Germany was passed. The local health department fulfilled the task of monitoring the test centers that subsequently opened throughout Cologne regarding the infectious and hygienic risks. Inspections were carried out using structured checklists. A retrospect evaluation of the identified deficiencies was run for the period between March 15 and July 31, 2021. In 84% of the cases, hygienic deficiencies were found when the test sites were inspected for the first time. 35% of the test sites were closed immediately, most of them temporarily. These first results provide information on frequent and important hygienic problems of the rapid set up of test sites and important advice for avoiding those and thus protecting employees and test persons.

Chemical hybridization of sulfasalazine and dihydroartemisinin promotes brain tumor cell death.

Gliomas are primary brain tumors with still poor prognosis for the patients despite a combination of cytoreduction via surgery followed by a radio-chemotherapy. One strategy to find effective treatment is to combine two different compounds in one hybrid molecule via linker to add to or at best potentiate their impact on malignant cells. Here, we report on the effects of a newly synthesized hybrid of sulfasalazine (SAS) and dihydroartemisinin (DHA), called AC254. In previous studies, both SAS and DHA have already proved to have anti-tumor properties themselves and to have sensitizing respectively potentiating effects on other treatments against malignant tumors. We investigated the impact of individual drugs SAS and DHA, their 1:1 combination and a novel SAS-DHA hybrid compound (AC254) on rodent and human glioma cells. In our study SAS alone showed no or only a mild effect on glioma, whereas DHA led to a significant reduction of cell viability in a dose-dependent manner. Next we compared the efficacy of the hybrid AC254 to the combinational treatment of its parent compounds SAS and DHA. The hybrid was highly efficient in combating glioma cells compared to single treatment strategies regarding cell viability and cell death. Interestingly, AC254 showed a remarkable advantage over the combinational treatment with both parent compounds in most used concentrations. In addition to its reduction of tumor cell viability and induction of cell death, the hybrid AC254 displayed changes in cell cycle and reduction of cell migration. Taken together, these results demonstrate that clinically established compounds such as SAS and DHA can be potentiated in their anti-cancer effects by chemical hybridization. Thus, this concept provides the opportunity to devise new effective chemotherapeutic agents.

Cytotoxic profiling of artesunic and betulinic acids and their synthetic hybrid compound on neurons and gliomas.

Gliomas are brain-born tumors with devastating impact on their brain microenvironment. Novel approaches employ multiple combinations of chemical compounds in synthetic hybrid molecules to target malignant tumors. Here, we report on the chemical hybridization approach exemplified by artesunic acid (ARTA) and naturally occurring triterpene betulinic acid (BETA). Artemisinin derived semisynthetic compound artesunic acid (ARTA) and naturally occurring triterpene BETA were used to synthetically couple to the hybrid compound termed 212A. We investigated the impact of 212A and its parent compounds on glioma cells, astrocytes and neurons. ARTA and BETA showed cytotoxic effects on glioma cells at micromolar concentrations. ARTA was more effective on rodent glioma cells compared to BETA, whereas BETA exhibited higher toxic effects on human glioma cells compared to ARTA. We investigated these compounds on non-transformed glial cells and neurons as well. Noteworthy, ARTA showed almost no toxic effects on astrocytes and neurons, whereas BETA as well as 212A displayed neurotoxicity at higher concentrations. Hence we compared the efficacy of the hybrid 212A with the combinational treatment of its parent compounds ARTA and BETA. The hybrid 212A was efficient in killing glioma cells compared to single compound treatment strategies. Moreover, ARTA and the hybrid 212A displayed a significant cytotoxic impact on glioma cell migration. Taken together, these results demonstrate that both plant derived compounds ARTA and BETA operate gliomatoxic with minor neurotoxic side effects. Altogether, our proof-of-principle study demonstrates that the chemical hybrid synthesis is a valid approach for generating efficacious anti-cancer drugs out of virtually any given structure. Thus, synthetic hybrid therapeutics emerge as an innovative field for new chemotherapeutic developments with low neurotoxic profile.