Synthesis, Cytotoxicity and Antimicrobial Activity of New Enmein-type Kauranoid Diterpenoid Derivatives

Author(s): Dahong Li, Tong Han, Xu Hu, Kangtao Tian, Shengtao Xu, Tingting Zhou, Keguang Cheng, Zhanlin Li, Huiming Hua, Jinyi Xu*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 17 , Issue 12 , 2017

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Graphical Abstract:


Background: Recently, we devoted to disclosing the antibacterial activities of enmein-type 6,7-seco-ent-kauranoid derivatives.

Objective: Eleven new enmein-type diterpenoid derivatives with different substituents and drug-like properties were designed and synthesized.

Method: 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.

Results: 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.

Conclusion: 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.

Keywords: Antiproliferative, antimicrobial, enmein-type, diterpenoid, SAR, derivatives.

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Article Details

Year: 2017
Published on: 12 April, 2017
Page: [1679 - 1688]
Pages: 10
DOI: 10.2174/1871521409666170412114648
Price: $65

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