Determination of bisphosphonate properties in terms of bioavailability, bone affinity, and cytotoxicity

The study aimed to evaluate the therapeutic potential of fourteen newly synthesized bisphosphonates by assessing their bioavailability, bone affinity, and cytotoxicity. These bisphosphonates included a series of aminomethylenebisphosphonates and standard compounds such as risedronate and tiludronate.

Drug permeability was determined using Parallel Artificial Membrane Permeability Assays (PAMPA), while bone affinity was assessed by sorption on hydroxyapatite. Bacterial cell response to the bisphosphonates was also examined using Lactobacillus paracasei cells as a model.

Several tested compounds, including BP3 to BP8 and BP11, which feature substituents in the pyridine ring such as methyl groups, iodine, bromine, chlorine, or hydroxyl groups, demonstrated potentially more beneficial therapeutic properties than commercially used bisphosphonates. These compounds showed stronger bone affinity and higher gastrointestinal absorption with comparable or lower cytotoxic effects. Specifically, BP11 exhibited the highest bone affinity, while BP8 and BP11 showed the greatest permeability.

The findings suggest that BP3 BP8, and BP11 are promising candidates for further research. These results highlight the importance of comprehensively evaluating bisphosphonates' therapeutic properties to identify effective treatments for osteoporosis and other bone diseases.