title: Synthesis, Cytotoxicity and Antimicrobial Activity of New Enmein-type Kauranoid Diterpenoid Derivatives.
abstract: Recently, we devoted to disclosing the antibacterial activities of enmein-type 6,7-seco-ent-kauranoid derivatives.
  
  
  
  Eleven new enmein-type diterpenoid derivatives with different substituents and drug-like properties were designed and synthesized.
  
  
  
  The antimicrobial activities against E. coli, S. aureus, B. subtilis and M. albicans were disclosed. The antiproliferative activities against human cancer Bel-7402, K562, MGC-803 and CaEs-17 cells and non-cancerous L-02 cells were also measured by MTT method.
  
  
  
  The results revealed that enmein-type diterpenoids showed more promising activities against tested gram-positive bacteria than gram-negative bacterium and fungus. Compound 9 with R of 2-quinolyl group exhibited the strongest antimicrobial activities with MIC values of 7.81 µg/ml and 0.98 µg/ml against S. aureus and B. subtilis, respectively. All the target derivatives exhibited superior cytotoxic activities to compounds 1 and 2 against tumor cells, and slight selectivity between cancerous cells and normal liver cells. Compound 12 with R of 3-(2-chloropyridyl) group and IC50 values of 0.7 µM, 0.9 µM, 0.8 µM and 2.0 µM agaist four tumor cells, respectively, was selected for further mechanism study in Bel-7402 cell line.
  
  
  
  Compound 12 could induce S phase cell cycle arrest and apoptosis at low concentrations via mitochondria-related pathways. The effects of compound 12 on some apoptosis related proteins showed that CDK2 was up regulated and ATM and cyclin A1 were down-regulated which confirmed the apoptosis and cell cycle effects.
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang. China.
authors.forename: Dahong
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Han
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang. China.
authors.forename: Kangtao
authors.initials: K
authors.lastname: Tian
authors.affiliation: Department of Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing. China.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Xu
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, and School of Chemistry and Pharmacy, Guangxi Normal University, Guilin. China.
authors.forename: Keguang
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang. China.
authors.forename: Zhanlin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang. China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Hua
authors.affiliation: Department of Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing. China.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Xu
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004224:Diterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D045786:Diterpenes, Kaurane / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D016196:S Phase / Q000187:drug effects; D013057:Spectrum Analysis / Q000379:methods; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D004224:Diterpenes; D045786:Diterpenes, Kaurane; C007594:enmein
keywords: Antiproliferative; SAR; antimicrobial; derivatives; diterpenoid; enmein-type