Trilobolide and its analogues belong to the guaianolide type of sesquiterpene lactones, which are characteristic and widely distributed within the families Asteraceae and Apiaceae. Certain guaianolides are receiving continuously increasing attention for their promising sarco-endoplasmic reticulum Ca2+-ATPase (SERCA)-inhibitory activity. However, because of their alkylation capabilities, they are generally toxic. Therefore, the search for compounds with significant immunobiological properties but with decreased cytotoxicities suitable for use in immune-based pharmacotherapy is ongoing. Therefore, we extended our previous investigation of the immunobiological effects of trilobolide to a series of structurally related guaianolides and germacranolides. To evaluate the relationship, we tested a series of selected derivatives containing α-methyl lactone or exomethylene lactone ring. For a wider comparison, we also included some of their glycosidic derivatives. We assessed the in vitro immunobiological effects of the tested compounds on nitric oxide (NO) production, cytokine secretion, and prostaglandin E2 (PGE2) release by mouse peritoneal cells, activated primarily by lipopolysaccharide (LPS), and evaluated their viability. The inhibitory effects of the apparently most active substance, 8-deoxylactucin, seem to be the most promising.

• Keywords
• 8-deoxylactucin, 8-epiisoamberboin, germacranolides, guaianolides, immune-modulatory effects,
• MeSH
• Butyrates MeSH
• Cytokines metabolism   MeSH
• Dinoprostone metabolism   biosynthesis   MeSH
• Furans MeSH
• Lactones * pharmacology   chemistry   MeSH
• Lipopolysaccharides pharmacology   MeSH
• Mice MeSH
• Nitric Oxide * metabolism   MeSH
• Macrophages, Peritoneal drug effects   metabolism   MeSH
• Sesquiterpenes, Germacrane * pharmacology   chemistry   MeSH
• Sesquiterpenes, Guaiane * pharmacology   chemistry   MeSH
• Sesquiterpenes pharmacology   chemistry   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Butyrates MeSH
• Cytokines MeSH
• Dinoprostone MeSH
• Furans MeSH
• germacranolide MeSH Browser
• Lactones * MeSH
• Lipopolysaccharides MeSH
• Nitric Oxide * MeSH
• Sesquiterpenes, Germacrane * MeSH
• Sesquiterpenes, Guaiane * MeSH
• Sesquiterpenes MeSH
• trilobolide MeSH Browser

Purpurin 18 derivatives with a polyethylene glycol (PEG) linker were synthesized as novel photosensitizers (PSs) with the goal of using them in photodynamic therapy (PDT) for cancer. These compounds, derived from a second-generation PS, exhibit absorption at long wavelengths; considerable singlet oxygen generation and, in contrast to purpurin 18, have higher hydrophilicity due to decreased logP. Together, these properties make them potentially ideal PSs. To verify this, we screened the developed compounds for cell uptake, intracellular localization, antitumor activity and induced cell death type. All of the tested compounds were taken up into cancer cells of various origin and localized in organelles known to be important PDT targets, specifically, mitochondria and the endoplasmic reticulum. The incorporation of a zinc ion and PEGylation significantly enhanced the photosensitizing efficacy, decreasing IC50 (half maximal inhibitory compound concentration) in HeLa cells by up to 170 times compared with the parental purpurin 18. At effective PDT concentrations, the predominant type of induced cell death was apoptosis. Overall, our results show that the PEGylated derivatives presented have significant potential as novel PSs with substantially augmented phototoxicity for application in the PDT of cervical, prostate, pancreatic and breast cancer.

• Keywords
• PEGylated purpurin 18, apoptosis, cancer cells, cytotoxicity, flow cytometry, live-cell fluorescence microscopy, photodynamic therapy, photosensitizer, phototoxicity, singlet oxygen,
• MeSH
• Microscopy, Fluorescence MeSH
• Photochemotherapy methods   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Porphyrins chemistry   MeSH
• Flow Cytometry MeSH
• Solubility MeSH
• Singlet Oxygen chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Porphyrins MeSH
• purpurin 18 MeSH Browser
• Singlet Oxygen MeSH