The known compounds cappariloside A and stachydrin, an adenosine nucleoside, and for the first time from plants of the Capparidaceae family the known compounds hypoxanthine and uracil were isolated from Capparis spinosa (Capparidaceae) fruit.Capparis spinosa (Capparidaceae) is widely distributed throughout the whole world. Information on alkaloids, flavonoids, and glycosides [1][2][3][4][5] in addition to lipids and carbohydrates [6] from this plant has been published.Herein we report a study of alkaloids from fruit of C. spinosa growing in Xinjiang Autonomy Region of China. The alcohol extract of ground and defatted ripe fruit of C. spinosa produced total extracted substances containing also water-soluble alkaloids of the betaine type. The lipophilic components were removed by washing the acidic solution of extracted substances with ether. The total alkaloids were obtained by treatment of the acidic solution with conc. ammonia to adjust the pH to 9 and extraction with n-butanol (fraction A). The dried alkaloidal fraction A was chromatographed over a silica-gel column with elution by CHCl 3 , CHCl 3 :CH 3 OH, and CH 3 OH. Work up with CH 3 OH of the CHCl 3 :CH 3 OH (12:1) fractions isolated amorphous hypoxanthine (1) and uracil (2) [7,8], which were identified using PMR and 13 C NMR spectral data and authentic samples (spectral properties are given in Experimental).Crystalline 3, mp 228-229°C, was isolated from CHCl 3 :CH 3 OH (10:1) fractions. The UV spectrum of 3 had absorption maxima at 206.4 and 259.6 nm. The IR spectrum had absorption bands for active H at 3425, 3370 (NH 2 ), 3320, and 3143 (OH) cm −1 ; lactone ring (tetrahydrofuran), 1680; ether, 1100 and 1030; and tri-and disubstituted aromatic rings, 1600, 1577, 870, 822, 795, and 765. The mass spectrum of 3 gave a peak for the molecular ion with m/z 267 and fragments with m/z 148 and 119 produced by cleavage of the tetrahydrofuran ring. Peaks for ions with m/z 134 and 133 corresponded to fragments formed by cleavage of the C-N bond between the main part of the molecule and the tetrahydrofuran ring. NMR data ( 1 H and 13 C) are given in Experimental.The spectral data (UV, IR, mass, NMR) were reminiscent of those of adenosine (3) [9]. However, the lack of an authentic sample prohibited reliable identification of 3 as adenosine. As a result, a single-crystal x-ray structure analysis (XSA) of 3 showed that the isolated base was in fact the known nucleoside adenosine (C 10 H 13 N 5 O 4 ), which is constructed from D-ribose and a purine base in which the N-9 atom of the purine base adenine is bonded to C-1 of D-ribose [10][11][12][13]. Adenosine
Bexarotene (BEX) was approved by the FDA in 1999 for the treatment of cutaneous T-cell lymphoma (CTCL). The poor aqueous solubility causes the low bioavailability of the drug and thereby limits the clinical application. In this study, we developed a GCN-based deep learning model (CocrystalGCN) for in-silico screening of the cocrystals of BEX. The results show that our model obtained high performance relative to baseline models. The top 30 of 109 coformer candidates were scored by CocrystalGCN and then validated experimentally. Finally, cocrystals of BEX-pyrazine, BEX-2,5-dimethylpyrazine, BEX-methyl isonicotinate, and BEX-ethyl isonicotinate were successfully obtained. The crystal structures were determined by single-crystal X-ray diffraction. Powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis were utilized to characterize these multi-component forms. All cocrystals present superior solubility and dissolution over the parent drug. The pharmacokinetic studies show that the plasma exposures (AUC0−8h) of BEX-pyrazine and BEX-2,5-dimethylpyrazine are 1.7 and 1.8 times that of the commercially available BEX powder, respectively. This work sets a good example for integrating virtual prediction and experimental screening to discover the new cocrystals of water-insoluble drugs.
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