Solen Josse

Controlled release of bisphosphonate from a calcium phosphate biomaterial inhibits osteoclastic resorption in vitro

Calcium phosphate biomaterials such as calcium deficient apatite (CDA) have been contemplated as carrier for delivery of bisphosphonate in bone tissues. In the present work, we have investigated the in vitro biological properties of Zoledronate-loaded CDA. CDA was loaded with zoledronate according to a previously described coating process. 31P MAS NMR spectra demonstrated the effective loading of zoledronate onto CDA. Using 14C labeled zoledronate, we then demonstrated the in vitro release of zoledronate from CDA. In a first set of experiments, we confirmed that Zoledronate reduced the number of TRAP-, vitronectin receptor-, and F-actin ring-positive cells as well as the resorption activity of osteoclasts obtained from a total rabbit bone cell culture. Interestingly, Zoledronate-loaded CDA and its extractive solutions decreased the osteoclastic resorption. Finally, zoledronate-loaded CDA did not affect the viability and alkaline phosphatase activity of primary osteoblastic cells. These data demonstrate that CDA is effective for loading and release of zoledronate. The released zoledronate inhibited osteoclastic resorption without affecting osteoblasts. Our findings therefore suggest that such a drug delivery system would allow an increase in the efficiency of bisphosphonates by being locally available. Further experiments are now required to evaluate the in vivo antiresorptive activity of this concept.

Preparation of Spiro[4.4]oxaphospholene and -azaphospholene Systems from Carbohydrate Templates

Introduction of a spiro-phosphorus cycle in position 3 of monosaccharidic derivatives was studied starting from cyanohydrin or aminonitrile A. A two-step procedure involving (i) phosphonylation and (ii) carbanion-mediated phosphonate intramolecular cyclization (denoted CPIC) was used. The necessity of having an electron-withdrawing group α to the phosphorus atom in order to avoid undesired reactions was demonstrated.

Synthesis of nucleoside analogs and new Tat protein inhibitors

Two studies, concerning the synthesis of original nucleoside analogs regarded as an application of heterochemistry on thiaazaheterocycle systems from thiaazabutadienes are discussed. The preparation of new N- and C-nucleosides is presented. In the second part, the discovery of aromatic polycyclic derivatives as inhibitors of Tat protein is exposed. The work presented takes into account the participation of African partners in further synthetic research programs carried out in collaboration with the laboratory of Nantes.

Rearrangement of 1-O-(thio-p-nitrobenzoyl)thiocarbonyl galactoside: a novel access to α-thioglycoside derivatives

The synthesis of galactosides thiolate and thioester is described by direct S-glycosylation process from 1-O-(thio-p-nitrobenzoyl)thiocarbonyl galactoside. Three novel anomeric groups are presented as potent glycoside activators: O-(thio-p-nitrobenzoyl)thiocarbonyl, O-(imidazolyl)thiocarbonyl and S-thio-p-nitrobenzoyl.

SYNTHESIS OF THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES

ABSTRACT The syntheses of thiazinone, thiazinedione and thiazolinone base modified nucleoside analogues have been discussed in both the deoxy- and ribosyl series. Both inter- and intramolecular N-glycosylations were evaluated.

Reactivity of 1,1'-thiocarbonyldiimidazole with glycosides: a novel and efficient glycosidic activation

Abstract The synthesis of monoglycosyl imidazoles and 1,1′-di- O -glycosides is described by direct glycosylation process from reducing sugar in the presence of 1,1′-thiocarbonyldiimidazole. Novel anomeric groups as 1- O -(imidazolyl)thiocarbonyl and 1- O -(imidazolyl)carbonyl are presented as potent glycosidic activators.