Sulfoglycolipids : new molecule for tumor treatment

Large number of glycoglycerolipids have been found in green, red and brown algae, which have been attracting a surge of interest due to the increased understanding of their wide spectrum of biological and pharmacological activities, including antitumor, anti-HIV, anti-inflammatory etc. The sulfoglycolipids are abundant sulfur-containing glycerolipids in the biotic world, sulfoquinovosylacylglycerols (SQAGs), occur in higher plants, other photosynthetic organisms and most of the marine water algae2, a sulfonic acid head group, 6-deoxy-6-sulfo-glucose, referred to as sulfoquinovose3 is major characteristic feature of SQAGs. Recent records of SQAGs biological activities, includes inhibitory effects on HIV-reverse transcriptase4, eukaryotic DNA polymerase5, proliferation of some cancer cell lines5, angiogenesis (especially when coupled with tumor radiotherapy)6 and also apoptosis induction5, make these compounds very attractive for their potential in cancer therapy. Also, extractive SQAG mixtures are known to inhibit in vitro TPA induced tumor promotion stage7. All of these above mentioned biological activities motivate us to synthesize new active compounds for cancer therapy by structural modifications of natural SQAGs. SQAG analogues (SQDG & SQMG) has been synthesized in which the sulfoquinovose moiety is β-linked to the 2 position of glycerol carrying acyl chains of different length with chemoenzymetic approach as well. Similar compounds, carrying a hydroxyl group instead of the sulfonate group (namely some glycoglycerolipid analogues), are known to be active as anti-tumor-promoters in TPA promoted carcinogenesis in vitro and in vivo experiments8,9. A synthetic strategy has been used to selectively insert the proper chemical functionalities (i.e. sulfonate and acyl chains) at the desired positions of the previously prepared glucosylglycerol skeleton to obtain the target compounds. LPS enzyme played an important role regarding selectivity at glycerol moiety. Biological evaluation of anti-tumor activities has been done including the anti-tumor-promoting properties of the obtained compounds. Compared this data of SQDG with the reported activities for glycoglycerolipid analogues8,9 it was possible to ascertain the influence of the sulfonate group on the anti-tumor-promoting activity.