Bisphosphonated Benzoxazinorifamycin Prodrugs for the Prevention and Treatment of Osteomyelitis

Reddy, Ranga; Dietrich, Evelyne; Lafontaine, Yanick; Houghton, Tom J.; Bélanger, Odette; Dubois, Anik; Arhin, Francis F.; Sarmiento, Ingrid; Fadhil, Ibtihal; Laquerre, Karine; Ostiguy, Valérie; Lehoux, Dario; Moeck, Greg; Parr, Thomas; Far, Adel Rafai

doi:10.1002/cmdc.200800255

Cited by 25 publications

(25 citation statements)

References 44 publications

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“…The most common treatments are antibiotics and surgery to remove portions of bone that are infected or dead. Thus, selective targeting of antibiotics to bone seems to be profitable, and some preliminary attempts to design and obtain osteotropic systems with fluoroquinones, [113,114] vancomycin [115] and rifamycin [116] as active components have been undertaken.…”

Section: Scheme (5) Examples Of Conjugates Of Bisphosphonates With Amentioning

confidence: 99%

Physiologic Activity of Bisphosphonates – Recent Advances

Chmielewska¹,

Kafarski

2016

PHARMSCI

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Section: Scheme (5) Examples Of Conjugates Of Bisphosphonates With Amentioning

confidence: 99%

Physiologic Activity of Bisphosphonates – Recent Advances

Chmielewska¹,

Kafarski

2016

PHARMSCI

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“…These compounds target the enzyme farnesyl diphosphate synthase (14) and are used in medicine for the treatment and prevention of osteoporosis, Paget's disease, hypercalcemia, tumor bone metastases, and other bone diseases (15,16). The drugs are selective because they can bind to the bone mineral (17). By replacing the carbon atom with different side chains, it is possible to generate a large variety of bisphosphonate derivatives.…”

mentioning

confidence: 99%

“…By replacing the carbon atom with different side chains, it is possible to generate a large variety of bisphosphonate derivatives. Interestingly, bisphosphonates also have antibacterial (17) and anticancer activities (18) and are able to stimulate ␥␦ T cells (19). Several of these compounds have antiparasitic action (20)(21)(22)(23).…”

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confidence: 99%

Synergistic Activity between Statins and Bisphosphonates against Acute Experimental Toxoplasmosis

Szajnman

et al. 2017

Antimicrob Agents Chemother

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Bisphosphonates are widely used for the treatment of bone disorders. These drugs also inhibit the growth of a variety of protozoan parasites, such as Toxoplasma gondii, the etiologic agent of toxoplasmosis. The target of the most potent bisphosphonates is the isoprenoid biosynthesis pathway enzyme farnesyl diphosphate synthase (FPPS). Based on our previous work on the inhibitory effect of sulfurcontaining linear bisphosphonates against T. gondii, we investigated the potential synergistic interaction between one of these derivatives, 1-[(n-heptylthio)ethyl]-1,1-bisphosphonate (C7S), and statins, which are potent inhibitors of the host 3-hydroxy-3-methyl glutaryl-coenzyme A reductase (3-HMG-CoA reductase). C7S showed high activity against the T. gondii bifunctional farnesyl diphosphate (FPP)/geranylgeranyl diphosphate (GGPP) synthase (TgFPPS), which catalyzes the formation of FPP and GGPP (50% inhibitory concentration [IC 50 ] ϭ 31 Ϯ 0.01 nM [mean Ϯ standard deviation]), and modest effect against the human FPPS (IC 50 ϭ 1.3 Ϯ 0.5 M). We tested combinations of C7S with statins against the in vitro replication of T. gondii. We also treated mice infected with a lethal dose of T. gondii with similar combinations. We found strong synergistic activities when using low doses of C7S, which were stronger in vivo than when tested in vitro. We also investigated the synergism of several commercially available bisphosphonates with statins both in vitro and in vivo. Our results provide evidence that it is possible to develop drug combinations that act synergistically by inhibiting host and parasite enzymes in vitro and in vivo.

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“…These conjugates were synthesized as bone-specific estrogens in the hope that they will protect elderly women from bone loss resulting from osteoporosis. A derivative of raloxifene, a selective estrogen receptor or modulator, was obtained using a suitable acid chloride as substrate [137], whereas radioligands, which are selectively bound to bone tissue, have been synthesized by using DCC/HOBt (hydroxybenzotriazol) activation [138] and antibacterial bisphosphonated benzoxazinorifamycin prodrugs using EDCl (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) [139].…”

Section: Direct Acylation Of Tetraethyl Aminobisphosphonatesmentioning

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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Bisphosphonated Benzoxazinorifamycin Prodrugs for the Prevention and Treatment of Osteomyelitis

Cited by 25 publications

References 44 publications

Physiologic Activity of Bisphosphonates – Recent Advances

Physiologic Activity of Bisphosphonates – Recent Advances

Synergistic Activity between Statins and Bisphosphonates against Acute Experimental Toxoplasmosis

Synthetic Procedures Leading towards Aminobisphosphonates

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