Copper-free click-chemistry platform to functionalize cisplatin prodrugs.
The ability to rationally design and construct a platform technology to develop new platinum(IV) [Pt(IV)] prodrugs with functionalities for installation of targeting moieties, delivery systems, fluorescent reporters from a single precursor with the ability to release biologically active cisplatin by using well-defined chemistry is critical for discovering new platinum-based therapeutics. With limited numbers of possibilities considering the sensitivity of Pt(IV) centers, we used a strain-promoted azide-alkyne cycloaddition approach to provide a platform, in which new functionalities can easily be installed on cisplatin prodrugs from a single Pt(IV) precursor. The ability of this platform to be incorporated in nanodelivery vehicle and conjugation to fluorescent reporters were also investigated.
NanoTherapeutics Research Laboratory, Department of Chemistry, University of Georgia, Athens, GA 30602 (USA), Fax: (+1) 706-542-9454 http://shanta.chem.uga.edu.
Rakesh K
RK
Pathak
Christopher D
CD
McNitt
Vladimir V
VV
Popik
Shanta
S
Dhar
D000480:Alkynes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology; D001386:Azides / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry* / Q000494:pharmacology; D057930:Click Chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D061565:Cycloaddition Reaction; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D049329:Nanostructures / Q000737:chemistry; D010084:Oxidation-Reduction; D010984:Platinum / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology
D000480:Alkynes; D000970:Antineoplastic Agents; D001386:Azides; D056831:Coordination Complexes; D004337:Drug Carriers; D011355:Prodrugs; D010984:Platinum; D003300:Copper; D002945:Cisplatin
cancer; cisplatin; click chemistry; nanoparticles; prodrugs