title: Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin.
abstract: Three series of novel sulfonylurea podophyllotoxin derivatives were designed, synthesized, and evaluated for in vitro cytotoxicity against four tumor cell lines (A-549, DU-145, KB and KBvin). Compounds 14c (IC₅₀: 1.41-1.76 μM) and 14e (IC₅₀: 1.72-2.01 μM) showed superior cytotoxic activity compared with etoposide (IC₅₀: 2.03 to >20 μM), a clinically available anticancer drug. Significantly, most of the compounds exhibited comparable cytotoxicity against the drug-resistant tumor cell line KBvin, while etoposide lost activity completely. Preliminary structure-activity relationship (SAR) correlations indicated that the 4'-O-methyl functionality in podophyllotoxin analogues may be essential to maintain cytotoxic activity, while an arylsulfonylurea side chain at podophyllotoxin's 4β position can significantly improve cytotoxic activity.
authors: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors: Zhi-Jun
authors: ZJ
authors: Zhang
authors: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors: Jing
authors: J
authors: Tian
authors: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
authors: Li-Ting
authors: LT
authors: Wang
authors: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors: Mei-Juan
authors: MJ
authors: Wang
authors: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors: Xiang
authors: X
authors: Nan
authors: Environmental and Municipal Engineering School, Lanzhou Jiaotong University, Lanzhou 730000, PR China.
authors: Liu
authors: L
authors: Yang
authors: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China. Electronic address: yqliu@lzu.edu.cn.
authors: Ying-Qian
authors: YQ
authors: Liu
authors: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
authors: Susan L
authors: SL
authors: Morris-Natschke
authors: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States; Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan. Electronic address: khlee@email.unc.edu.
authors: Kuo-Hsiung
authors: KH
authors: Lee
mesh_terms: D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D006801:Humans; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D013453:Sulfonylurea Compounds; D011034:Podophyllotoxin
keywords: Cytotoxic activity; Podophyllotoxin; Sulfonylurea; Synthesis