Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery
نویسندگان
چکیده
Pyrazolo[3,4-d]pyrimidines are a class of compounds with a good activity against several cancer cell lines. Despite the promising anticancer activity, these molecules showed a poor aqueous solubility. This issue could threat the future development of pyrazolo[3,4-d]pyrimidines as clinical drug candidates. With the aim of improving their solubility profile and consequently their pharmacokinetic properties, we have chosen four compounds (1-4) on the base of their anti-neuroblastoma activity and we have developed albumin nanoparticles and liposomes for the selected candidates. Albumin nanoparticles and liposomes were prepared and characterized regarding size and ζ-potential distribution, polidispersity index, entrapment efficiency and activity against SH-SY5Y human neuroblastoma cell line. The most promising nanosystem, namely LP-2, was chosen to perform further studies: confocal microscopy, stability and drug release in physiological conditions, and biodistribution. Altogether, the obtained data strongly indicate that the encapsulation of pyrazolo[3,4-d]pyrimidines in liposomes represent an effective method to overcome the poor water solubility.
منابع مشابه
The Metabolism of Pyrazolo(3,4-Ã-/)pyrimidines by the Rat't
The recent development of a new series of carcinostatic purine analogs, the pyrazolo(3,4-d)pyrimidines (5), has led to their study as substrates and inhibitors of certain purine oxidation systems in vitro (1,4). In the course of these studies, it was observed that purified xanthine oxidase incubated in vitro with 4-aminopyrazolo(3,4-d)pyrimidine (pyrazoloadenine) resulted in its oxidation to 4a...
متن کاملRegioselectivity of 1,3-dipolar cycloadditions and antimicrobial activity of isoxazoline, pyrrolo[3,4-d]isoxazole-4,6-diones, pyrazolo[3,4-d]pyridazines and pyrazolo[1,5-a]pyrimidines.
BACKGROUND Isoxazoles exhibit interesting biological activities, and the 1,3-dipolar cycloaddition(13DC) reactions play an important role in both mechanistic and synthetic organic chemistry. Pyrazoles and annulated pyrazoles exhibit some diverse biological activities. They are used as antipyretic, analgesic drugs, tranquilizing, and herbicidal agents. Pyrazoles are also used extensively as usef...
متن کاملA major mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) is the lowering of prostaglandin (PG) production through inhibition of the cyclooxygenase
Accepted September 28, 2012 In the present study, a series of benzothiazol derivatives 3a-l containing pyrazolo[3,4-d]pyrimidine moiety at the second position were synthesized and characterized by analytical and spectral data. The compounds were tested for their in vitro antimicrobial activity. Compounds 1-(1,3-benzothiazol-2yl)-3-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidine (3a), 1(1,3-benzoth...
متن کاملSynthesis and biological evaluation of some novel pyrazolopyrimidines incorporating a benzothiazole ring system.
In the present study, a series of benzothiazol derivatives 3a-l containing pyrazolo[3,4-d]pyrimidine moiety at the second position were synthesized and characterized by analytical and spectral data. The compounds were tested for their in vitro antimicrobial activity. Compounds 1-(1,3-benzothiazol-2- yl)-3-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidine (3a), 1- (1,3-benzothiazol-2-yl)-4-(4-chlorop...
متن کاملThe metabolism of pyrazolo (3,4-d) pyrimidines by the rat.
The recent development of a new series of carcinostatic purine analogs, the pyrazolo(3,4-d)pyrimidines (5), has led to their study as substrates and inhibitors of certain purine oxidation systems in vitro (1,4). In the course of these studies, it was observed that purified xanthine oxidase incubated in vitro with 4-aminopyrazolo(3,4-d)pyrimidine (pyrazoloadenine) resulted in its oxidation to 4a...
متن کامل