Back to Search
Start Over
Lasiokaurin derivatives: synthesis, antimicrobial and antitumor biological evaluation, and apoptosis-inducing effects
- Source :
- Archives of Pharmacal Research. 40:796-806
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Herein, a series of lasiokaurin derivatives were designed and synthesized. All the derivatives together with lasiokaurin and oridonin were tested for their antimicrobial and antiproliferative activity. Compound 16 showed the most promising antimicrobial activity with MICs of 2.0 and 1.0 μg/mL against Gram-Positive bacteria S. aureus and B. subtilis, respectively. All the synthetic lasiokaurin derivatives showed better antiproliferative activity than parent compound lasiokaurin 1. Compound 10 exhibited the strongest cytotoxicity with IC50 values of 0.47 and 0.20 μM against MGC-803 and CaEs-17 cells, accordingly. Moreover, it was shown to have potent antitumor activity in vivo in a murine model of MGC-803 gastric cancer. Preliminary SARs were also concluded based on obtained data. The apoptosis-inducing effects of 10 were further investigated using CaEs-17 cells. The results showed that lasiokaurin derivative 10 could induce apoptosis via mitochondria related pathway and arrest CaEs-17 cell cycle at S phase. Compound 10 could also affect apoptosis-related proteins that was up-regulation of CDK2 and down-regulation of ATM and cyclin A1.
- Subjects :
- 0301 basic medicine
Down-Regulation
Antineoplastic Agents
Apoptosis
Microbial Sensitivity Tests
Mitochondrion
Biology
Pharmacology
Inhibitory Concentration 50
Mice
03 medical and health sciences
Anti-Infective Agents
Stomach Neoplasms
In vivo
Drug Discovery
Animals
Humans
Cytotoxicity
Cell Proliferation
Mice, Inbred BALB C
Organic Chemistry
Cyclin-dependent kinase 2
Cell cycle
Antimicrobial
Up-Regulation
030104 developmental biology
S Phase Cell Cycle Checkpoints
biology.protein
Molecular Medicine
Female
Diterpenes
Drug Screening Assays, Antitumor
Diterpenes, Kaurane
Cyclin A1
Subjects
Details
- ISSN :
- 19763786 and 02536269
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Archives of Pharmacal Research
- Accession number :
- edsair.doi.dedup.....654cbd8f651800fdadbf1a430abf9ca0