Ningbo Gong

Identification of Less Lipophilic Riminophenazine Derivatives for the Treatment of Drug-Resistant Tuberculosis

Clofazimine (CFZ), a member of the riminophenazine class, has been studied in clinical trials for the treatment of multidrug-resistant tuberculosis (MDR-TB). CFZ has several side effects which can be attributed to its extremely high lipophilicity. A series of novel riminophenazine analogues bearing a C-2 pyridyl substituent was designed and synthesized with the goal of maintaining potent activity against Mycobacterium tuberculosis (M. tuberculosis) while improving upon its safety profile by lowering the lipophilicity. All compounds were evaluated for their in vitro activity and cytotoxicity. The results demonstrated that many new compounds had potent activity against M. tuberculosis with MICs of less than 0.03 μg/mL and low cytotoxicity with IC(50) values greater than 64 μg/mL. Some compounds were tested for in vivo efficacy against MDR-TB in an experimental mouse infection model. Two compounds demonstrated equivalent or better efficacy than CFZ in this model with significantly reduced skin discoloration potential.

Studies on Solvatomorphism of Betulinic Acid

Five solvates of betulinic acid with dimethyl sulfoxide (I), methanol (II), ethanol (III), isopropyl alcohol (IV), and 2-butanol (V) have been described in this work. Methods of X-ray crystallography, thermal analysis, and Fourier transform infrared spectroscopy were introduced for solvatomorphic identifications and characterizations. The orientation of isopropenyl and carboxylic groups might differ because of single-bonding rotations. The incorporation of solvents resulted in changes of the crystal symmetry, intermolecular arrangements, stoichiometry, hydrogen bonding interactions, and so on. Adducted solvents contributed most to the stability of crystal lattices and led to the formation of crystalline forms. Solvates II-V with their single-crystal structures determined have been reported for the first time.

Purity assessment of luteolin reference material candidates by coulometric titration method

A reliable, sensitive, and rapid coulometric titration (CT) method was developed for the purity determination of luteolin reference material candidates. The results obtained from the proposed CT method were compared with those obtained from differential scanning calorimetry (DSC) and mass balance method. The performance of the CT method was comparable, and the quantitative results of the proposed methods were in good agreement with those of DSC and mass balance methods. CT has the advantages of minimal sample requirement, rapid measurement, high accuracy, good reproducibility, and no corresponding reference standard requirement. This method can be used for luteolin purity assays and related production quality control.

Fimbriatols A-J, Highly Oxidized ent-Kaurane Diterpenoids from Traditional Chinese Plant Flickingeria fimbriata (B1.) Hawkes.

Fimbriatols A–J (1–10), ten new ent-kaurane diterpenoids possessing differently highly oxidized sites, were isolated from Flickingeria fimbriata (B1.) Hawkes. The structures of these new compounds were determined by HRESI-MS, NMR, CD spectra and X-ray diffraction analysis. Compound 1 displayed moderately inhibitory ratio (48.5%) compared with the positive compound NSC-87877 (81.6%) at the concentration of 0.022 μg/mL. Compounds 7–10 possess 3, 4-seco-ent-kaurane skeleton containing a disaccharide moiety with an unusual linkage at C-2′ to C-1′′ instead of the common linkage at C-6′ to C-1′′, and this is the first report in 600 more ent-kauranes found in nature, which might be originated from ent-kaurane diterpenoids through post-modified reactions of Baeyer-Villiger oxygenation and glycosylation.

Isostructurality Among 5 Solvatomorphs of Betulin: X-Ray Structure and Characterization

Betulin (BE), a triterpene found in many plant species, has recently attracted the attention of researchers because of its important physiological and pharmacological properties, such as anti-HIV and anticancer activities. Studies have revealed the solvatomorphism of BE (I with dimethyl sulfoxide and III with ethanol, named by author), which means more solvatomorphs may be obtained when different solvents are used during crystallization. After solid-form screening tests, 3 new solvatomorphs of BE with methanol (II), n-propanol (IV), and isopropanol (V) were obtained. In this work, 5 BE solvatomorphs were characterized by X-ray powder diffractometric, thermogravimetric, and Fourier transform infrared spectroscopic analyses. Single-crystal X-ray diffraction was used to analyze the X-ray structures of the compounds, and all 5 solvatomorphs were proven to be isostructral. Change in the crystal symmetry, intermolecular arrangements, stoichiometry, and hydrogen bonding interactions of the solvatomorphs resulted from solvent incorporation to the solvates. Solvatomorphs II, IV, and V, along with their single-crystal structures, were reported for the first time.

Polymorphs and Versatile Solvates of 7-Hydroxyisoflavone.

7-hydroxyisoflavone has been crystallized, identified, and characterized as 2 solvent-free conformational polymorphs and 5 solvates, which differ from each other in the mode of packing and in molecular conformation. All the 7 crystal structures were previously unreported. The conformational polymorphs and solvates were compared by Hirshfeld surface and fingerprint plot analysis and were spectroscopically characterized by powder X-ray diffraction, differential scanning calorimetry, and thermal gravimetric analysis. Hydrogen bond played an important role in the formation of polymorphs. From this study, we can predict that more solvates could be cultivated in other polarity solvents such as isopropanol or 2-butanol at appropriate conditions.

Characterization and uncertainty evaluation of a new certified reference material of baicalein

A new certified reference material (CRM) of baicalein was developed aiming to control the quality of baicalein and relative pharmaceuticals. Sample preparation, homogeneity, stability, value assignment, and uncertainty of a new certified reference material (CRM) of baicalein were presented in this paper. Characterization of the material relied on three different methods, which were differential scanning calorimetry (DSC), coulometric titration method (CT) and mass balance method. DSC and CT were used for purity determination of baicalein firstly. The certified value of baicalein CRM is 99.72% with an expanded uncertainty of 0.25% (k=2). The new CRM of baicalein can be used to validate analytical methods, improve the accuracy of measurement data as well as establish meteorological traceability of analytical results.

Development of a new ferulic acid certified reference material for use in clinical chemistry and pharmaceutical analysis

This study compares the results of three certified methods, namely differential scanning calorimetry (DSC), the mass balance (MB) method and coulometric titrimetry (CT), in the purity assessment of ferulic acid certified reference material (CRM). Purity and expanded uncertainty as determined by the three methods were respectively 99.81%, 0.16%; 99.79%, 0.16%; and 99.81%, 0.26% with, in all cases, a coverage factor (k) of 2 (P=95%). The purity results are consistent indicating that the combination of DSC, the MB method and CT provides a confident assessment of the purity of suitable CRMs like ferulic acid.

Development of a new certified reference material of diosgenin using mass balance approach and Coulometric titration method

Certified reference materials (CRMs) can be used as a valuable tool to validate the trueness of measurement methods and to establish metrological traceability of analytical results. Diosgenin has been selected as a candidate reference material. Characterization of the material relied on two different methods, mass balance method and Coulometric titration method (CT). The certified value of diosgenin CRM is 99.80% with an expanded uncertainty of 0.37% (k=2). The new CRM of diosgenin can be used to validate analytical methods, improve the accuracy of measurement data and control the quality of diosgenin in relevant pharmaceutical formulations.

Preparation and characterization a new certified reference material of puerarin (GBW09511)

Sample preparation, homogeneity study, stability study, value characterization, and evaluation of uncertainty of a new certified reference material (CRM) of puerarin are presented in this paper. The homogeneity was checked by a differential scanning calorimetry method. The stability was tested under different storage conditions. The CRM described above was homogeneous and stable at 25 °C for at least one year. The certified value of puerarin CRM is 99.66% with an extended uncertainty of 0.48% (k = 2). Coulometric titration and differential scanning calorimetry methods are used for purity determination of puerarin for the first time in this paper. The new CRM of puerarin can be used to validate analytical methods, improve the accuracy and comparability of measurement data, establish meteorological traceability of analytical results as well as control the quality of puerarin in relevant food and pharmaceutical formulations.