title: Design, synthesis and cytotoxic activity of a novel series of steroidal phenylpyrazoles.
abstract: Thirty novel steroidal pyrazole derivatives were designed and synthesized via a highly efficient route from pregnenolone (1) as starting material. The key intermediates 3a-c were obtained under Vilsmeier conditions, and the subsequent hydrolysis, acetylation or Borch reduction afforded thirty target compounds. These compounds were mainly characterized by (1)H NMR, (13)C NMR, DEPT135°. The structure of compound 3a was also confirmed by X-ray single crystal diffraction. The cytotoxicity of these compounds was evaluated by the SRB method against four cancer cell lines, including A549, Hela, MCF-7 and HepG2, and the results indicated that compounds 5a, 6a, 7a and 8a exhibited significant cytotoxicity with IC50 values ranging from 0.91 to 5.44 μM. Most importantly, compound 5a exhibited excellent cytotoxicity against A549 with an IC50 value of 0.91 μM. On the basis of our research the structure-activity relationships (SAR) of these compounds were discussed. This work provides some important hints for further structural modification of steroids towards developing novel and highly effective anticancer drugs.
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Ximei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Longbo
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Tan
authors.affiliation: Key Laboratory of Botanical Pesticide R & D in Shaanxi Province, Yangling 712100, Shaanxi, China. Electronic address: shibaojun@nwsuaf.edu.cn.
authors.forename: Baojun
authors.initials: B
authors.lastname: Shi
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China; Key Laboratory of Botanical Pesticide R & D in Shaanxi Province, Yangling 712100, Shaanxi, China. Electronic address: nwzjw@nwsuaf.edu.cn.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Zhang
mesh_terms: D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003603:Cytotoxins; D011720:Pyrazoles; D013256:Steroids
keywords: Antiproliferative activity; Pregnenolone; Pyrazole; Steroids