title: Synthesis of novel strobilurin-pyrimidine derivatives and their antiproliferative activity against human cancer cell lines.
abstract: A series of new strobilurin-pyrimidine analogs were designed and synthesized based on the structures of our previously discovered antiproliferative compounds I and II. Biological evaluation with two human cancer cell lines (A549 and HL60) showed that most of these compounds possessed moderate to potent antiproliferative activity. Two potent candidates (8f, IC50=2.2 nM and 11d, IC50=3.4 nM) were identified with nanomolar activity against leukemia cancer cell line HL60 for further development. This activity represents a 1000- to 2500-fold improvement compared to the parent compounds I and II and is 20- to 30-fold better than the chemotherapy drug, doxorubicin. The present work provides strong incentive for further development of these strobilurin-pyrimidine analogs as potential antitumor agents for the treatment of leukemia.
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China.
authors.forename: Baoshan
authors.initials: B
authors.lastname: Chai
authors.forename: Shuyang
authors.initials: S
authors.lastname: Wang
authors.forename: Wenquan
authors.initials: W
authors.lastname: Yu
authors.forename: Huichao
authors.initials: H
authors.lastname: Li
authors.forename: Chuanjun
authors.initials: C
authors.lastname: Song
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Changling
authors.initials: C
authors.lastname: Liu
authors.forename: Junbiao
authors.initials: J
authors.lastname: Chang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D005231:Fatty Acids, Unsaturated; D008689:Methacrylates; D011743:Pyrimidines