title: Design and synthesis of novel pyrazolo[1,5-a]pyrimidine derivatives bearing nitrogen mustard moiety and evaluation of their antitumor activity in vitro and in vivo.
abstract: A series of novel pyrazolo[1,5-a]pyrimidine derivatives bearing nitrogen mustard moiety were designed, synthesized and evaluated for their antiproliferative activities against five human cancer cell lines (A549, SH-SY5Y, HepG2, MCF-7 and DU145) in vitro. Among these compounds, 13b exhibited potent inhibitory effect on the proliferation of the five tumor cells and was able to inhibit cell cycle arrest at G1 phase and induce cell apoptosis. In HepG2 HCC xenograft compound 13b was selected for evaluating the antitumor activity in vivo which exhibited significant cancer growth inhibition with low host toxicity in vivo.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Ren
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Diqin
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Yating
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China; Experimental Chemistry Center, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China. Electronic address: qicmin@sohu.com.
authors.forename: Chuanmin
authors.initials: C
authors.lastname: Qi
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Huabei
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008466:Mechlorethamine / Q000737:chemistry*; D051379:Mice; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D008466:Mechlorethamine
keywords: Anti-tumor; Apoptosis; Cell cycle; Nitrogen mustard derivatives; Pyrazolo[1,5-a]pyrimidine; Xenograft mice model