ABSTRACT
A series of novel tetrandrine (Tet) derivatives were synthesized through Suzuki -Miyaura reaction and evaluated for their cytotoxicity against human non-small cell lung carcinoma (NSCLC) A549 cells. Interestingly, most of derivatives showed similar cytotoxicity to Tet against NSCLC A549 cells, and particularly, compounds Y5, Y6, Y9 and Y11 showed the most significant cytotoxic effects with IC50 values ranging from 3.87 to 4.66 mM. The present study is expected to contribute to the future design of more effective anticancer agents in lung cancer chemotherapy.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Benzylisoquinolines/chemistry , Benzylisoquinolines/pharmacology , A549 Cells , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Carcinoma, Non-Small-Cell Lung , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Molecular StructureABSTRACT
Astragali Radix (AR) is one of the most popular herbal medicines in traditional Chinese medicine (TCM). Wild AR is believed to be of high quality, and substitution with cultivated AR is frequently encountered in the market. In the present study, two types of ARs (wild and cultivated) from Astragalus membranaceus (Fisch.) Bge. and A. membranaceus var. mongholicus (Bge.) Hsiao, growing in different regions of China, were analyzed by NMR profiling coupled with multivariate analysis. Results showed that both could be differentiated successfully and cultivation patterns or growing years might have greater impact on the metabolite compositions than the variety; the metabolites responsible for the separation were identified. In addition, three extraction methods were compared and the method (M1) was used for further analysis. In M1, the extraction solvent composed of water, methanol, and chloroform in the ratio of 1 : 1 : 2 was used to obtain the aqueous methanol (upper layer) and chloroform (lower layer) fractions, respectively, showing the best separation. The differential metabolites among different methods were also revealed. Moreover, the sucrose/glucose ratio could be used as a simple index to differentiate wild and cultivated AR. Meanwhile, the changes of correlation pattern among the differential metabolites of the two varieties were found. The work demonstrated that NMR-based non-targeted profiling approach, combined with multivariate statistical analysis, can be used as a powerful tool for differentiating AR of different cultivation types or growing years.
Subject(s)
Astragalus propinquus/chemistry , Magnetic Resonance Spectroscopy/methods , Plant Extracts/chemistry , Astragalus propinquus/classification , Astragalus propinquus/metabolism , China , Metabolomics , Plant Extracts/metabolism , Plant Roots/chemistry , Plant Roots/classification , Plant Roots/growth & development , Plants, Medicinal/chemistry , Plants, Medicinal/growth & development , Plants, Medicinal/metabolismABSTRACT
A series of tetrandrine derivatives were designed and synthesized using Suzuki coupling reaction. Eleven targeted compounds with over 50% inhibition against HL60 and A549 human cancer cell lines at 10 µM were further evaluated for the in vitro antitumor activities by MTT or SRB assay. The biological results revealed that some compounds exhibited potent antitumor activities. Thiophene derivative 6 and acetylphenyl derivative 5 were the most active ones against HL60 and A549 cell lines, with IC50 values less than 5 µM, which thus could be considered as useful candidate for further development of new antitumor agents.
Subject(s)
Antineoplastic Agents/chemical synthesis , Benzylisoquinolines/chemical synthesis , Benzylisoquinolines/pharmacology , Drug Design , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Benzylisoquinolines/chemistry , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Molecular Structure , Structure-Activity RelationshipABSTRACT
The study established the 1H NMR-based fingerprinting and analyzed 8 batches of Huangqi injection solution.1H NMR-based fingerprinting of both primary and secondary metabolites of Huangqi injection were established, and the 1H-1H chemical shift correlation spectroscopy (COSY) and 1H-13C chemical shift correlation spectroscopy (HSQC) were used to identify the chemical components in Huangqi injection solution. Coupled with similarity analysis and relative content determination,8 batches of Huangqi injection solution were analyzed. Twenty-five metabolites (both primary and secondary) were identified, and the significant differences were found in the chemical composition among these Huangqi samples. The content and content variation of the primary metabolites were much higher than those of the secondary metabolites, which was the major cause of the uniformity of the Huangqi injections. The results on the quality variations of Huangqi injections in this study will serve as a basis for improving the quality control.
