Design, Synthesis and Labeling of Tripeptide Derivatives with 99mTc as Hypoxia Imaging Agents
نویسندگان
چکیده مقاله:
Background: Many diseases, including cancer, ischemia and tumors show degrees of tissue hypoxia.Therefore, it is useful to detect tissue hypoxia with compounds that can penetrate and remain in hypoxic cells in order to diagnose cancer at early stages. Peptides with low molecular weight, susceptible to redox environment, with easier penetration into tissues and low antigenic characteristics are good candidates,as compared to antibodies and proteins. Therefore, radiolabeling small lipophilic peptides containing a nitro group with 99mTc to enter and remain in the hypoxic cell for imaging hypoxic tissue is a good strategy for earlier detection of tumors, which leads to more effective and satisfactory treatment. Materials and Methods: In this study, some tripeptides were synthesized with added para nitro benzoic acid (PNBA) group at their N-terminal using solid phase peptide synthesis (SPPS) method with Fmocstrategy using Wang resin. The peptides were labeled with 99mTc and their characterizations were determined using chromatographic techniques and partition coefficient experiments. A hypoxia Jar system was used to examine cellular uptake of the labeled peptides exposed to MCF-7 cells in normal and hypoxic conditions for 30 to 120 min. Results: Synthesis of the peptides resulted in good yields (70% to 78%). The synthesized peptides andradiopeptides were stable in normal saline and human plasma for at least 4 h and 6 h, respectively.Radiochemical purity (RCP) of the synthesized labeled peptides was 94% with lipophilicity (Log P) -0.006. Furthermore, labeled peptides exposed to MCF-7 cells could remain in hypoxic cells longer than those in normal cells. Conclusion: Considering the results obtained in this study, the peptide derivatives labeled with 99mTc,appear to be appropriate agents for the detection and imaging of hypoxic tissues.
منابع مشابه
Design and Synthesis of 2-Methyl and 2-Methyl-4-Nitro Imidazole Derivatives as Antifungal Agents
Two series (a and b) of N- substituted heteroaromatic compounds related to clotrimazole were synthesized. Imidazole ring of the clotrimazole was replaced by 2-methylimidazole in series a, and by 2-methyl-4-nitroimidazole in series b. O-cholortrityl moiety of clotrimazole was also replaced by trityl, mono or dimethoxy trityl. Chemical structures...
متن کاملDesign and Synthesis of Pyrrolo[2,1-a]Isoquinoline-Based Derivatives as New Cytotoxic Agents
A new series of anti-cancer agents based on 1,2-diaryl-5,6-dihydropyrrolo[2,1-a]isoquinoline scaffold containing N,N-diethylaminoethoxy, piperidinylethoxy or morpholinylethoxy group at the para position of the C-2 phenyl ring were synthesized and their cytotoxic activities were assessed against several human cancer cell lines including MCF-7 (ER positive breast cancer cell), MDA-MB231 (ER-ne...
متن کاملDesign and Synthesis of Pyrrolo[2,1-a]Isoquinoline-Based Derivatives as New Cytotoxic Agents
A new series of anti-cancer agents based on 1,2-diaryl-5,6-dihydropyrrolo[2,1-a]isoquinoline scaffold containing N,N-diethylaminoethoxy, piperidinylethoxy or morpholinylethoxy group at the para position of the C-2 phenyl ring were synthesized and their cytotoxic activities were assessed against several human cancer cell lines including MCF-7 (ER positive breast cancer cell), MDA-MB231 (ER-ne...
متن کاملDesign and Synthesis of 4-flurophthalimides as potential anticonvulsant agents
Objective(s): Anticonvulsant activity of phthalimide was discovered in 2000 by molecular hybridization of thalidomide and ameltolide. In our previous research we have reported some new 4-substituted derivatives of phthalimide with good activity against the tonic and clonic seizures Material and Methods: A series of novel 4-flurophthalimides that designed using bioisosteric replacement were synt...
متن کاملDesign and Synthesis of 4-flurophthalimides as potential anticonvulsant agents
Objective(s): Anticonvulsant activity of phthalimide was discovered in 2000 by molecular hybridization of thalidomide and ameltolide. In our previous research we have reported some new 4-substituted derivatives of phthalimide with good activity against the tonic and clonic seizures Material and Methods: A series of novel 4-flurophthalimides that designed using bioisosteric replacement were synt...
متن کاملمنابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ذخیره در منابع من قبلا به منابع من ذحیره شده{@ msg_add @}
عنوان ژورنال
دوره 22 شماره 3
صفحات 160- 173
تاریخ انتشار 2019-08
با دنبال کردن یک ژورنال هنگامی که شماره جدید این ژورنال منتشر می شود به شما از طریق ایمیل اطلاع داده می شود.
کلمات کلیدی برای این مقاله ارائه نشده است
میزبانی شده توسط پلتفرم ابری doprax.com
copyright © 2015-2023