title: Low toxicity and unprecedented anti-osteoclast activity of a simple sulfur-containing gem-bisphosphonate: a comparative study.
abstract: Bisphosphonates (BPs) are key drugs for the treatment of bone resorption diseases like osteoporosis, Paget's disease and some forms of tumors. Recent findings underlined the importance of lipophilic N-containing BPs to ensure high biological activity. Herein we present some unprecedented results concerning the low toxicity and good anti-osteoclast activity of low molecular weight hydrophilic S-containing BPs. A series of S and N-containing BPs bearing aromatic and aliphatic substitution were prepared through Michael addition reaction between vinylidenebisphosphonate tetraethyl ester and the proper nucleophile under basic catalysis. S-containing BPs showed a generally low toxicity, determined with the neutral-red assay using the L929 cell line, and, in particular for an aliphatic one, a good biological activity assessed on primary cultures of human osteoclasts.
authors.affiliation: Laboratorio di Fisiopatologia Ortopedica e Medicina Rigenerativa, Istituto Ortopedico Rizzoli, via di Barbiano 1/10, I-40136 Bologna, Italy. donatella.granchi@ior.it
authors.forename: Donatella
authors.initials: D
authors.lastname: Granchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Scarso
authors.forename: Giulio
authors.initials: G
authors.lastname: Bianchini
authors.forename: Andrea
authors.initials: A
authors.lastname: Chiminazzo
authors.forename: Alberto
authors.initials: A
authors.lastname: Minto
authors.forename: Paolo
authors.initials: P
authors.lastname: Sgarbossa
authors.forename: Rino A
authors.initials: RA
authors.lastname: Michelin
authors.forename: Gemma
authors.initials: G
authors.lastname: Di Pompo
authors.forename: Sofia
authors.initials: S
authors.lastname: Avnet
authors.forename: Giorgio
authors.initials: G
authors.lastname: Strukul
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism; D004164:Diphosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D015394:Molecular Structure; D008970:Molecular Weight; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry*
chemical_list: D004164:Diphosphonates; D013455:Sulfur; D003094:Collagen
keywords: Apoptosis; Bisphosphonates; Cytotoxicity; Osteoclast; S-containing drugs