Synthesis and in vitro evaluation of bisphosphonated glycopeptide prodrugs for the treatment of osteomyelitis

Tanaka, Kelly S.E.; Dietrich, Evelyne; Ciblat, Stéphane; Métayer, Claude; Arhin, Francis F.; Sarmiento, Ingrid; Moeck, Greg; Parr, Thomas; Far, Adel Rafai

doi:10.1016/j.bmcl.2010.01.006

Cited by 27 publications

(19 citation statements)

References 46 publications

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“…Therefore, beyond the role of bisphosphonates in carrying drugs to bone, bisphosphonates may help improve bone healing during infection. Bisphosphonates conjugated to select glycopeptide antibiotics, vancomycin and oritavancin, have been developed and have high binding to bone in vitro [87]. Despite conjugation, the compounds continue to have efficacy in vitro against microbes, presumably upon dissociation of the conjugated compounds [87].…”

Section: 0 Bodymentioning

confidence: 99%

“…Bisphosphonates conjugated to select glycopeptide antibiotics, vancomycin and oritavancin, have been developed and have high binding to bone in vitro [87]. Despite conjugation, the compounds continue to have efficacy in vitro against microbes, presumably upon dissociation of the conjugated compounds [87]. Several studies have gone on to explore the potential of bisphosphonate-conjugated antimicrobials in vivo .…”

Section: 0 Bodymentioning

confidence: 99%

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Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis

Ford

Cassat

2017

Expert Review of Anti-infective Therapy

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Structured Abstract Introduction Osteomyelitis, a common and debilitating invasive infection of bone, is a frequent complication following orthopedic surgery and causes pathologic destruction of skeletal tissues. Bone destruction during osteomyelitis results in necrotic tissue, which is poorly penetrated by antibiotics and can serve as a nidus for relapsing infection. Osteomyelitis therefore frequently necessitates surgical debridement procedures, which provide a unique opportunity for targeted delivery of antimicrobial and adjunctive therapies. Areas Covered Following surgical debridement, tissue voids require implanted materials to facilitate the healing process. Antibiotic-loaded, non-biodegradable implants have been the standard of care. However, a new generation of biodegradable, osteoconductive materials are being developed. Additionally, in the face of widespread antimicrobial resistance, alternative therapies to traditional antibiotic regimens are being investigated, including bone targeting compounds, antimicrobial surface modifications of orthopedic implants, and anti-virulence strategies. Expert Commentary Recent advances in biodegradable drug delivery scaffolds make this technology an attractive alternative to traditional techniques for orthopedic infection that require secondary operations for removal. Advances in novel treatment methods are expanding the arsenal of viable antimicrobial treatment strategies in the face of widespread drug resistance. Despite a need for large scale clinical investigations, these strategies offer hope for future treatment of this difficult invasive disease.

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Section: 0 Bodymentioning

confidence: 99%

Section: 0 Bodymentioning

confidence: 99%

Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis

Ford

Cassat

2017

Expert Review of Anti-infective Therapy

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“…Alkylation of tetraalkyl methylenebisphosphonate 45, a classical method for synthesizing variable bisphosphonic acids, has been rarely used for the synthesis of amino derivatives. Thus, its direct amination with the hydroxylamine ester of diphenylphosphinic acid, followed by its bromoacetylation (Scheme 23), provided substrate 46 for functionalization into glycopeptide antibiotics, in the hope that they will find an application as medication for osteomyelitis [117]. Another classical example is the monoalkylation of tetraisopropyl methylenebisphosphonate with 1,6-dibromohexane, followed by fluorination with Selectofluor and conversion of the remaining bromide into amine, which resulted in compound 47 (Scheme 23) [118].…”

Section: Miscellaneous Proceduresmentioning

confidence: 99%

Synthetic Procedures Leading towards Aminobisphosphonates

Chmielewska

Kafarski

2016

Molecules

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Abstract:Growing interest in the biological activity of aminobisphosphonates has stimulated the development of methods for their synthesis. Although several general procedures were previously elaborated to reach this goal, aminobisphosphonate chemistry is still developing quite substantially. Thus, innovative modifications of the existing commonly used reactions, as well as development of new procedures, are presented in this review, concentrating on recent achievements. Additionally, selected examples of aminobisphosphonate derivatization illustrate their usefulness for obtaining new diagnostic and therapeutic agents.

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“…Systemic antibiotic administration combined with surgical removal of infected and necrotic tissues is used conventionally to treat IRO [45]. Various local methods have been developed to prevent [30,44] and treat [25] IRO.…”

Section: Introductionmentioning

confidence: 99%