title: Novel hybrids of natural oridonin-bearing nitrogen mustards as potential anticancer drug candidates.
abstract: A series of novel hybrids from natural product oridonin and nitrogen mustards were designed and synthesized to obtain more efficacious and less toxic antitumor agents. The antiproliferative evaluation showed that most conjugates were more potent than their parent compounds oridonin and clinically used nitrogen mustards against four human cancer cell lines (K562, MCF-7, Bel-7402, and MGC-803). Furthermore, the representative compounds 16a-c exhibited antiproliferative activities against the multidrug resistant cell lines (SW620/AD300 and NCI-H460/MX20). It was shown that the most effective compound 16b possesses a strong inhibitory activity with an IC50 value 21-fold lower than that of oridonin in MCF-7 cells and also exhibits selective cytotoxicity toward the cancer cells. Intriguingly, compound 16b has been demonstrated to significantly induce apoptosis and affect cell cycle progression in human hepatoma Bel-7402 cells.
authors: State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, China.
authors: Shengtao
authors: S
authors: Xu
authors: State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, China.
authors: Lingling
authors: L
authors: Pei
authors: State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, China.
authors: Chengqian
authors: C
authors: Wang
authors: College of Pharmacy and Health Sciences, St. John's University , 8000 Utopia Parkway, Queens, New York 11439, United States.
authors: Yun-Kai
authors: YK
authors: Zhang
authors: State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, China ; Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University , 103 Wen Hua Road, Shenyang 110016, China.
authors: Dahong
authors: D
authors: Li
authors: State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, China.
authors: Hequan
authors: H
authors: Yao
authors: State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, China.
authors: Xiaoming
authors: X
authors: Wu
authors: College of Pharmacy and Health Sciences, St. John's University , 8000 Utopia Parkway, Queens, New York 11439, United States.
authors: Zhe-Sheng
authors: ZS
authors: Chen
authors: Drug Screening Center, Nanjing Key Gen Biotech. Co., Ltd. , Nanjing 210012, China.
authors: Yijun
authors: Y
authors: Sun
authors: State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, China.
authors: Jinyi
authors: J
authors: Xu
keywords: Oridonin; antiproliferative activities; apoptosis; combination principle; drug-resistant; nitrogen mustards