title: Multiobjective optimization on antiplatelet effects of three components combination by quantitative composition-activity relationship modeling and weighted-sum method.
abstract: Multicomponent therapeutic has become an increasingly favored strategy for treating complex diseases in recent years. In this study, a multiple objective optimization approach was proposed to design the optimal combination of three components for antiplatelet activity. The platelet aggregation assays induced by three different ways, adenosine diphosphate, arachidonic acid, and collagen, were applied to evaluate the in vitro antiplatelet activities of three active components derived from a traditional Chinese medicine. After analyzing this dataset by quantitative composition-activity relationship modeling, a weighted-sum optimization method was adopted to calculate the optimal ratio between three components for antiplatelet effects. Further experiments validated our method and showed that better antiplatelet activity was exerted by the optimized combination than the individual component or other combinations. Our findings suggested that the proposed multiobjective optimization approach is a novel method for multicomponent drug design.
authors.affiliation: Pharmaceutical Informatics Institute, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D011817:Rabbits; D015203:Reproducibility of Results
chemical_list: D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen
keywords: Xue-Fu-Zhu-Yu Tang; antiplatelet aggregation; quantitative composition-activity relationship; traditional Chinese medicine; weighted-sum method