A novel approach to active compounds identification based on support vector regression model and mean impact value.
Traditionally, active compounds were discovered from natural product extracts by bioassay-guided fractionation, which was with high cost and low efficiency. A well-trained support vector regression model based on mean impact value was used to identify lead active compounds on inhibiting the proliferation of the HeLa cells in curcuminoids from Curcuma longa L. Eight constituents possessing the high absolute mean impact value were identified to have significant cytotoxicity, and the cytotoxic effect of these constituents was partly confirmed by subsequent MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and previous reports. In the dosage range of 0.2-211.2, 0.1-140.2, 0.2-149.9 μm, 50% inhibiting concentrations (IC50 ) of curcumin, demethoxycurcumin, and bisdemethoxycurcumin were 26.99 ± 1.11, 19.90 ± 1.22, and 35.51 ± 7.29 μm, respectively. It was demonstrated that our method could successfully identify lead active compounds in curcuminoids from Curcuma longa L. prior to bioassay-guided separation. The use of a support vector regression model combined with mean impact value analysis could provide an efficient and economical approach for drug discovery from natural products.
Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin Key Laboratory of Biological and Pharmaceutical Engineering, Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China. jljiang@tju.edu.cn
Jian-Lan
JL
Jiang
Xin
X
Su
Huan
H
Zhang
Xiao-Hang
XH
Zhang
Ying-Jin
YJ
Yuan
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001681:Biological Assay / Q000379:methods; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D036381:Diarylheptanoids; D055808:Drug Discovery / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D060388:Support Vector Machine
D000970:Antineoplastic Agents; D003603:Cytotoxins; D036381:Diarylheptanoids; C034786:bisdemethoxycurcumin; D003474:Curcumin; C050229:demethoxycurcumin