title: Design of new arylamino-2-ethane-1,1-diyl- and benzoxazole-2-methylene-bisphosphonates vs cytotoxicity and chronic inflammation diseases. From hydrophobicity prediction to synthesis and biological evaluation.
abstract: A general synthetic approach to two new series of methylenebisphosphonates: arylamino-2-ethane-1,1-diyl- and benzoxazole-2-methylenebisphosphonates is presented. Acid hydrolysis of selected BPs was undertaken to give the corresponding bisphosphonic acid (BP-acid). Next, the prediction of the permeability (hydrophobicity) of the target compounds was measured, by a combination of RP-HPLC and computational techniques, to study the capacity of transporting the molecule through cellular membranes. Cytotoxicity/growth inhibition of 50% (GI(50), mg/L) and antichronic inflammation properties of the products were evaluated. Later on, a comparison of the pharmacological results with water-octanol partition coefficients (log K(OW)) of the compounds was also reported.
authors.affiliation: Chemical Industries Division, National Research Centre, Elbohouth St., D-12311 Dokki, Cairo, Egypt. wabdou@link.net
authors.forename: Wafaa M
authors.initials: WM
authors.lastname: Abdou
authors.forename: Reham F
authors.initials: RF
authors.lastname: Barghash
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Sediek
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000494:pharmacology; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D006801:Humans; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000188:drug therapy*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D000442:Octanols; D010539:Permeability; D012710:Serum Albumin, Bovine; D012995:Solubility; D014867:Water
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D001583:Benzoxazoles; D003603:Cytotoxins; D004164:Diphosphonates; D000442:Octanols; C029180:methylated bovine serum albumin; D014867:Water; D012710:Serum Albumin, Bovine