133081-25-1Relevant articles and documents
Facile synthesis of rapamycin-peptide conjugates as mTOR and Akt inhibitors
Singh, Shalini,Ali, Rafat,Miyan, Javed,Singh, Varsha,Meena, Sanjeev,Hasanain, Mohammad,Bhadauria, Smrati,Datta, Dipak,Sarkar, Jayanta,Haq, Wahajul
, p. 4352 - 4358 (2021)
A simple and straightforward process for the synthesis of rapamycin peptide conjugates in a regio and chemoselective manner was developed. The methodology comprises the tagging of chemoselective functionalities to rapamycin and peptides which enables the conjugation of free peptides, without protecting the functionality of the side chain amino acids, in high yield and purity. From this methodology, we successfully conjugate free peptides containing up to 15 amino acids. Rapamycin is also conjugated to the peptides known for inhibiting the kinase activity of Akt protein. These conjugates act as dual target inhibitors and inhibit the kinase activity of both mTOR and Akt. This journal is
Synthesis, physicochemical and biological evaluation of tacrine derivative labeled with technetium-99m and gallium-68 as a prospective diagnostic tool for early diagnosis of Alzheimer's disease
Gniazdowska, Ewa,Ko?miński, Przemys?aw,Halik, Pawe?,Bajda,Czarnecka, Kamila,Mikiciuk-Olasik, El?bieta,Mas?owska, Katarzyna,Rogulski, Zbigniew,Cheda, ?ukasz,Kilian, Krzysztof,Szymański, Pawe?
, (2019)
Design, physicochemical and biological studies of novel radioconjugates for the early diagnosis of Alzheimer's disease, based on the newly synthesized tacrine derivatives were performed. Novel tacrine analogues were labeled with technetium-99m and gallium-68. For all obtained radioconjugates ([99mTc]Tc-Hynic-(tricine)2NH(CH2)ntacrine and [68Ga]Ga-DOTA-NH(CH2)9tacrine, where n = 2–9 denotes the number of methylene groups CH2) the studies of physicochemical properties (lipophilicity, stability in the presence of an excess of standard amino acids cysteine or histidine, human serum and in cerebrospinal fluid) were performed. For two selected radioconjugates [99mTc]Tc-Hynic-(tricine)2NH(CH2)9Tac and [68Ga]Ga-DOTA-NH(CH2)9tacrine (characterized with the highest lipophilicity values) the biological tests (inhibition of cholinesterases action, molecular docking and biodistribution studies) have been performed. All novel radioconjugates showed high stability in biological solutions used. Both selected radioconjugates proved to be good inhibitors of cholinesterases and be able to cross the blood-brain barrier. Radioconjugates [99mTc]Tc-Hynic-(tricine)2NH(CH2)9tacrine and [68Ga]Ga-DOTA-NH(CH2)9tacrine fulfil the conditions for application in nuclear medicine. Radiopharmaceutical [68Ga]Ga-DOTA-NH(CH2)9tacrine, due to increased accuracy and improved sensitivity in PET imaging, may be better potential diagnostic tool for early diagnosis of Alzheimer's disease.
Synthesis and biological activity of derivatives of tetrahydroacridine as acetylcholinesterase inhibitors
Szymanski, Pawel,Markowicz, Magdalena,Mikiciuk-Olasik, Elbieta
, p. 138 - 142 (2011)
Current state of medical sciences does not allow to treatment neurodegenerative diseases such as Alzheimer's disease (AD). At present treatment of AD is severely restricted. The main class of medicines which are applied in AD is acetylcholinesterase inhibitors (AChEIs) like tacrine, donepezil, galantamine and rivastigmine that do not contribute to significant and long-term improvement in cognitive and behavioural functions. In this work, we report synthesis and biological evaluation of new hybrids of tacrine-6-hydrazinonicotinamide. The synthesis was based on the condensation reaction between tacrine derivatives and the hydrazine nicotinate moiety (HYNIC). All obtained compounds present affinity for both cholinesterases and are characterized by high selectivity in relation to butyrylcholinesterase (BChE).
PSMA inhibitor, application thereof and PSMA-targeting nuclide imaging reagent
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Paragraph 0045; 0049, (2020/06/20)
The invention belongs to the technical field of biological medicines, and particularly relates to a PSMA inhibitor, an application thereof and a PSMA-targeting nuclide imaging reagent. The PSMA inhibitor has a structure as shown in a formula I. The PSMA-targeting nuclide imaging reagent prepared by adopting EDDA as a co-ligand has good PSMA targeting property and affinity; high stability is realized in normal saline and mouse serum; meanwhile, the cell uptake amount is relatively high, and the metabolic performance is good. Therefore, the inhibitor has a good clinical application prospect in tumor imaging of targeted PSMA.