Abstract
A series of spiroisoxazoline analogues of artemisinin was synthesized by employing 1,3-dipolar cycloaddition between various in situ generated nitrile oxides and artemisitene. All the synthesized compounds were tested for their anti-proliferative and anti-malarial activities. Among the compounds tested, compound 11a was found to be potent against the HCT-15 cancer cell line with IC 50 = 4.04 μM when compared to 5-fluorouracil (IC 50 = 35.53 μM). DNA cell cycle analysis shows that 11a was inhibiting cell proliferation at the G2/M phase. Compound 11b was found to be most active against Plasmodium falciparum with IC 50 = 0.1 μM and also blocked host hemoglobin hydrolysis by the falcipain-3 receptor. It was demonstrated to have better dynamics of parasite killing efficiency than artemisinin. Molecular docking studies revealed that these compounds interacted with falcipain-3 receptor sites.
Original language | English (US) |
---|---|
Article number | 1800192 |
Journal | Archiv der Pharmazie |
Volume | 352 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2019 |
Externally published | Yes |
Keywords
- 1,3-dipolar cycloaddition
- anti-malarial activity
- anti-proliferative
- artemisitene
- spiroisoxazoline
ASJC Scopus subject areas
- Pharmaceutical Science
- Drug Discovery