A library of thirty two 3,4-diphenylfuranones related to both combretastatin A-4 and antifungal 5-(acyloxymethyl)-3-(halophenyl)-2,5-dihydrofuran-2-ones was prepared. Cytotoxic effects on a panel of cancer and normal cell lines and antiinfective activity were evaluated, and the data were complemented with tests for the activation of caspase 3 and 7. High cytotoxicity was observed in some of the halogenated analogues, eg. 3-(3,4-dichlorophenyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one with IC50 0.12-0.23 μM, but the compounds were also highly toxic against non-malignant control cells. More importantly, notable antibacterial activity indicating G+ selectivity has been found in the 3,4-diarylfuranone class of compounds for the first time. Hydroxymethylation of furanone C5 knocked out cytotoxic effects (up to 40 μM) while maintaining significant activity against Staphylococcus strains in some derivatives. MIC95 of the most promising compound, 3-(4-bromophenyl)-5,5-bis(hydroxymethyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one against S. aureus strain ATCC 6538 was 0.98 μM (0.38 μg/mL) and 3.9 μM (1.52 μg/mL) after 24 and 48 h, respectively.

• Keywords
• Antibacterial, Combretafuranone, Combretastatin analogue, Cytotoxic, Furanone, Synthesis,
• MeSH
• Anti-Bacterial Agents chemical synthesis   chemistry   pharmacology   MeSH
• Antifungal Agents chemical synthesis   chemistry   pharmacology   MeSH
• Apoptosis drug effects   MeSH
• Bacteria drug effects   MeSH
• Furans chemical synthesis   chemistry   pharmacology   MeSH
• Fungi drug effects   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Molecular Structure MeSH
• Cell Proliferation drug effects   MeSH
• Cell Survival drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Antifungal Agents MeSH
• Furans MeSH

Abstract Reactive oxygen species (ROS) and reactive nitrogen species have generally been considered as being highly reactive and cytotoxic molecules. Besides their noxious effects, ROS participate in physiological processes in a carefully regulated manner. By way of example, microbicidal ROS are produced in professional phagocytes, ROS function as short-lived messengers having a role in signal transduction and, among other processes, participate in the synthesis of the iodothyronine hormones, reproduction, apoptosis and necrosis. Because of their ability to mediate a crosstalk between key molecules, their role might be dual (at least in some cases). The levels of ROS increase from a certain age, being associated with various diseases typical of senescence. The aim of this review is to summarize the recent findings on the physiological role of ROS. Other issues addressed are an increase in ROS levels during ageing, and the possibility of the physiological nature of this process.

• MeSH
• Humans MeSH
• Reactive Nitrogen Species physiology   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Signal Transduction physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Reactive Nitrogen Species MeSH
• Reactive Oxygen Species MeSH