2. Academic Validation
  3. Novel hybrids of natural oridonin-bearing nitrogen mustards as potential anticancer drug candidates

Novel hybrids of natural oridonin-bearing nitrogen mustards as potential anticancer drug candidates

  • ACS Med Chem Lett. 2014 May 28;5(7):797-802. doi: 10.1021/ml500141f.
Shengtao Xu 1,  Lingling Pei 1,  Chengqian Wang 1,  Yun-Kai Zhang 2,  Dahong Li 3,  Hequan Yao 1,  Xiaoming Wu 1,  Zhe-Sheng Chen 2,  Yijun Sun 4,  Jinyi Xu 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, China.
  • 2 College of Pharmacy and Health Sciences, St. John's University , 8000 Utopia Parkway, Queens, New York 11439, United States.
  • 3 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.
  • 4 Drug Screening Center, Nanjing Key Gen Biotech. Co., Ltd. , Nanjing 210012, China.
PMID: 25050168 DOI: 10.1021/ml500141f
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.

Keywords

Oridonin; antiproliferative activities; apoptosis; combination principle; drug-resistant; nitrogen mustards.

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