Synthesis, Biological Activity, and Apoptotic Properties of NO-Donor/Enmein-Type ent-Kauranoid Hybrids

International Journal of Molecular Sciences

Xu Hu¹  Zhenzhong Wang¹  Huiming Hua¹  Shengtao Xu¹  Keguang Cheng²  Dahong Li³  Zhanlin Li³  Tong Han³  Tingting Zhou³  Jinyi Xu⁴  Wei Xiao⁵ 

[1]Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China

[2]Department of Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

[3]

[4]Key Laboratory of Structure-Based Drug Design &State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, and School of Chemistry and Pharmacy, Guangxi Normal University, Guilin 541004, China

[5]State Key Laboratory of New-Tech for Chinese Medicine Pharmaceutical Processes, and National Post-Doctoral Research Workstation, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China

关键词: NO-donor;    enmein-type;    ent-kauranoid;    antiproliferative;    apoptosis;   

DOI  :  10.3390/ijms17060747

来源: DOAJ

【 摘 要 】

Herein, we reported on a series of synthetic nitric oxide-releasing enmein-type diterpenoid hybrids (9a–i). All the target compounds showed potent antibacterial activity against selected Gram-positive bacteria S. aureus and B. subtilis. The antiproliferative activity against human tumor K562, MGC-803, CaEs-17 and Bel-7402 cells, and human normal liver cells L-02 was tested and the structure activity relationships (SARs) were also concluded. Compounds 9b and 9d showed the best activity against S. aureus and B. subtilis with the same minimal inhibitory concentrations (MICs) of 4 and 2 μg/mL, respectively. The derivative 9f displayed IC50 values of 1.68, 1.11, 3.60 and 0.72 μM against the four cancer cell lines above and 18.80 μM against normal liver cells L-02; meanwhile, 9f also released a high level of NO at the time point of 60 min of 22.24 μmol/L. Furthermore, it was also found that 9f induced apoptosis via the mitochondria-related pathway and arrested cell cycle of Bel-7402 cells at S phase. These findings might be important to explore new chemical entities for the main causes of in-hospital mortality of S. aureus infection, combined with a solid tumor.

【 授权许可】

Unknown