Fourteen diterpenes were isolated from methanol extracts of the aerial parts ofColeus comosus,Coleus forsteri "Marginatus", and Plectranthus ciliatus. The compounds belong to the abietane (1-4, 9-11, and 13), ent-clerodane (5-8), and ent-kaurane (14, 15) classes. Three new compounds were isolated from C. comosus, including 3-O-acetylornatin G (2), 3,12-di-O-acetylornatin G (3), ornatin B methyl ester (5), and ornatin F (4), for which we proposed a revised structure. The structures of the compounds were determined by comprehensive spectroscopic data analysis. The isolated diterpenes were examined in silico for their physicochemical and early ADME properties. Their antiproliferative effects were determined in vitro using human breast (MDA-MB-231 and MCF-7), cervical (HeLa), and glioblastoma (U-87 MG) cancer cell lines. The royleanone- and hydroquinone-type abietane diterpenes (9-13)exhibited the most potent antiproliferative activity against all cancer cell lines tested, particularly against glioblastoma cells, with IC50 values ranging from 1.1 to 15.6 μM.

• Publication type
• Journal Article MeSH

Cancer cells generally possess higher levels of reactive oxygen species than normal cells, and this can serve as a possible therapeutic target. In this proof-of-concept study, an antioxidant-inspired drug discovery strategy was evaluated using a hydroxycinnamic acid derivative. The processing of oxidized mixtures of p-coumaric acid methyl ester (pcm) revealed a new antitumor lead, graviquinone. Graviquinone bypassed ABCB1-mediated resistance, induced DNA damage in lung carcinoma cells but exerted DNA protective activity in normal keratinocytes, and modulated DNA damage response in MCF-7 cells. The cytotoxic effect of pcm in MCF-7 cells was potentiated under H2O2-induced oxidative stress, and the formation of graviquinone was confirmed by Fenton's reaction on pcm. In silico density functional theory calculations suggested graviquinone as a kinetic product of pcm-scavenging •OH radicals. Our results demonstrate the pharmacological value of an in situ-formed, oxidative stress-related metabolite of an antioxidant. This might be of particular importance for designing new strategies for antioxidant-based drug discovery.

• MeSH
• Drug Resistance, Neoplasm drug effects   MeSH
• Cyclohexanones pharmacology   toxicity   MeSH
• Hydroxyl Radical chemistry   MeSH
• Coumaric Acids chemistry   metabolism   pharmacology   MeSH
• Humans MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Drug Discovery MeSH
• Oxidation-Reduction MeSH
• Computer Simulation MeSH
• DNA Damage drug effects   MeSH
• Antineoplastic Agents pharmacology   toxicity   MeSH
• Free Radical Scavengers pharmacology   toxicity   MeSH
• Signal Transduction drug effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

AIM: In out of hospital cardiac arrest (OHCA) the start of Cardiopulmonary Resuscitation (CPR) by a single rescuer may be delayed considerably if the total time (TT) to connect the telephone call to the Emergency Medical Communication Centre (EMCC) is prolonged. EUROCALL investigated the TT-EMCC and its components using different calling procedures. METHODS: This prospective, multicentre, randomised study was performed in April 2013. Telephone calls were randomly allocated to time of call, and to those connecting directly to the EMCC (1-step procedure) and those diverted before connecting to the EMCC (2-step procedure). RESULTS: Twenty-one EMCCs from 11 countries participated in the study. Time to first ringtone was similar between 1-step 3.7s (IQR 1.0-5.2) and 2-step calls 4.0s (IQR 2.4-5.2). For the 1878 1-step calls, the median TT-EMCC was 11.7s (IQR 8.7-18.5). For the 1550 2-step calls, the median time from first ringtone to first call-taker was 7s (IQR 4.6-11.9) and from first call-taker to EMCC was 18.7s (IQR 13.4-29.9). Median TT-EMCC was 33.2 s (IQR 24.7-46.1) and was significantly longer than the TT-EMCC observed with the 1-step procedure (P<0.0001). Significant differences existed among participating regions between and within different countries both for 1-step and 2-step procedures. CONCLUSION: TT-EMCC was significantly shorter in a 1-step procedure compared to a 2-step procedure. Regional differences existed between countries but also within countries. This may be relevant in cases of OHCA and other situations where patient outcome is critically time-dependent.

• MeSH
• Time Factors MeSH
• Cardiopulmonary Resuscitation MeSH
• Humans MeSH
• Prospective Studies MeSH
• Telephone * MeSH
• Emergency Medical Services * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• Europe MeSH

• MeSH
• Critical Illness therapy   MeSH
• Humans MeSH
• Resuscitation standards   MeSH
• Heart Arrest etiology   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH
• Geographicals
• Europe MeSH

• Publication type
• Meeting Abstract MeSH

• MeSH
• DNA radiation effects   MeSH
• Humans MeSH
• DNA Damage MeSH
• Ultraviolet Rays adverse effects   MeSH
• Check Tag
• Humans MeSH

• MeSH
• Unconsciousness MeSH
• Criminal Law MeSH

• Conspectus
• Trestní právo
• NML Fields
• neurologie
• právo, zákonodárství
• NML Publication type
• brožury

• Conspectus
• Psychologie
• NML Fields
• psychologie, klinická psychologie
• sociologie

• MeSH
• Biomedical Engineering MeSH
• Keratinocytes MeSH
• Tissue Culture Techniques MeSH
• Skin, Artificial MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• biomedicínské inženýrství
• dermatovenerologie
• transplantologie