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. 2021 Jun 17;10(6):732. doi: 10.3390/antibiotics10060732

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Molecular structure and empirical formula of antibiotics and conjugates: (1) HBCS, (2) BCS, (3) Sitafloxacin hydrate, (4) HPHBP, (5) PHBP, (6) HBCT, (7) BCT, (8) BET, (9) Tedizolid, (10) APHBP, (11) APBP, (12) CPBP were synthesized according to procedures reported by Sun et al. and Sedghizadeh et al. [28,31]. All compounds were characterized by NMR, mass spec, elemental analyses and HPLC demonstrating high purity. On cleavage of the carbamate linkage of (1), (2), (6), (7), the released bisphosphonates (4), (5), (10), (11) and CO₂ are pharmacologically inactive components. Since cleavage of the linker and release of antibiotic occurs mainly at sites of higher bone resorption caused by osteoclastic or bacterial osteolysis, extremely high local concentrations of antibiotic are generated beneath or in the proximity of infections on bone surfaces. Conjugate (8) utilizes an ester linkage which appears to cleave more readily than carbamate comparators in vitro and will be compared for efficacy in vivo.