We investigated cytotoxic effects of the anthraquinone derivatives 1'-deoxyrhodoptilometrin (SE11) and (S)-(-)-rhodoptilometrin (SE16) isolated from the marine echinoderm Comanthus sp. in two tumor cell lines (C6 glioma, Hct116 colon carcinoma). Both compounds showed cytotoxic effects, with SE11 [IC-value (MTT assay): 13.1 µM in Hct116 cells] showing a higher potency to induce apoptotic and necrotic cell death. No generation of oxidative stress was detectable (DCF assay), and also no modulation of Nrf2/ARE and NFκB signaling could be shown. Investigation of 23 protein kinases associated with cell proliferation, survival, metastasis, and angiogenesis showed that both compounds were potent inhibitors of distinct kinases, e.g., IGF1-receptor kinase, focal adhesion kinase, and EGF receptor kinase with SE11 being a more potent compound (IC values: 5, 18.4 and 4 µM, respectively). SE11 caused a decrease in ERK phosphorylation which may be a consequence of the inhibition of EGF receptor kinase by this compound. Since an inhibition of the EGF receptor/MAPK pathway is an important target for diverse cytostatic drugs, we suggest that the anthraquinone derivative 1'-deoxyrhodoptilometrin (SE11) may be an interesting lead structure for the development of new anticancer drugs.

Fifteen pyrrole alkaloids were isolated from the Red Sea marine sponge Stylissa carteri and investigated for their biological activities. Four of them were dibrominated [(+) dibromophakelline, Z-3-bromohymenialdisine, (±) ageliferin and 3,4-dibromo-1H-pyrrole-2-carbamide], nine compounds were monobrominated [(-) clathramide C, agelongine, (+) manzacidin A, (-) 3-bromomanzacidin D, Z-spongiacidin D, Z-hymenialdisine, 2-debromostevensine, 2-bromoaldisine and 4-bromo-1H-pyrrole-2-carbamide)] and finally, two compounds were non-brominated derivatives viz., E-debromohymenialdisine and aldisine. The structure elucidations of isolated compounds were based on 1D & 2D NMR spectroscopic and MS studies, as well as by comparison with literature. In-vitro, Z-spongiacidin D exhibited a moderate activity on (ARK5, CDK2-CycA, CDK4/CycD1, VEGF-R2, SAK and PDGFR-beta) protein kinases. Moreover, Z-3-bromohymenialdisine showed nearly similar pattern. Furthermore, Z-hymenialdisine displayed a moderate effect on (ARK5 & VEGF-R2) and (-) clathramide C showed a moderate activity on AURORA-A protein kinases. While, agelongine, (+) manzacidin A, E-debromohymenialdisine and 3,4-dibromo-1H-pyrrole-2-carbamide demonstrated only marginal inhibitory activities. The cytotoxicity study was evaluated in two different cell lines. The most effective secondary metabolites were (+) dibromophakelline and Z-3-bromohymenialdisine on L5178Y. Finally, Z-hymenialdisine, Z-3-bromohymenialdisine and (±) ageliferin exhibited the highest cytotoxic activity on HCT116. No report about inhibition of AURORA-A and B by hymenialdisine/hymenialdisine analogs existed and no reported toxicity of ageliferin existed in literature.

Background People who have become victims of domestic or public violence often suffer long-term physical, psychological and social impairment. Due to physical injury, the first contact with the health care system is frequently an A & E Department. Thus, physicians and especially surgeons play a key role in detecting victims of domestic or public violence. The specific needs of victims are adequate medical treatment of injuries, forensic documentation, as well as interdisciplinary medical support to prevent further morbidity and violence. To take this into account, so-called expertise centres for victims of violence have been established at several locations in Germany in recent years. In this study: I. We tried to define the characteristics of victims of domestic and public violence to ensure better identification by physicians/surgeons. II. We elucidate the acceptance and effectiveness of such an expertise centre one year after its implementation and for a period of three years (2007 – 2009) and for a follow-up period of three years (2014 – 2016) after establishment. Material and Methods Patients were prospectively classified as victims of violence by the attending physician at the A & E Department and further treatment was initiated by the expertise centre for victims of violence. Medical reports from the A & E Department were analysed anonymously and compared with the number of patients of the expertise centre for victims of violence who had been referred from A & E Department. Results Orthopaedic and trauma surgery is the main referring discipline for the expertise centre for victims of violence. 0.9% of patients (2007 – 2009) and in the follow-up period (2014 – 2016) even 1.6% of patients were identified as victims of violence. However, the acceptance of such a centre fell from 22.2% (2007 – 2009) to 17.2% (2014 – 2016). Conclusion Physicians and especially trauma surgeons are responsible for identifying victims of domestic or public violence and ensuring further treatment. Accordingly, it is crucial that the expertise centre should characterise the victims of violence and be aware of their different needs, if the expertise centre is to be accepted. The results of this study indicate that interdisciplinary training and close cooperation between traumatology and legal medicine are the main prerequisites for continuous improvement in the treatment of victims of violence.

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