Anti-cancer activity of novel dibenzo[b,f]azepine tethered isoxazoline derivatives

BMC Chem Biol. 2012 Oct 3:12:5. doi: 10.1186/1472-6769-12-5.

Abstract

Background: Dibenzoazepine (DB) derivatives are important and valuable compounds in medicinal chemistry. The synthesis and chemotherapeutic properties of naturally occurring DBs and different heterocyclic moiety tethered DBs are reported. Herein, we report the DB-fused hybrid structure that containing isoxazolines (DBIs) and their anti-cancer activity, which could throw light on the structural and functional features of new molecules.

Results and conclusion: The synthesis and characterization of novel ring DB tethered isoxazoline derivatives (DBIs) were carried out. After the detailed structural characterization using 2D-NMR experiments, the compounds were identified as 5-substituted isoxazolines. The effect of newly synthesized DBIs against the invasion of murine osteosarcoma (LM8G7) cells was studied. Among the tested molecules, compound 4g (5-[-3-(4-chlorophenyl)-4,5-dihydroisoxazol-5-yl-methyl]-5 H-dibenzo[b,f]azepine), was found to inhibit the invasion of LM8G7 cells strongly, when compared to other structurally related compounds. Cumulatively, the compound 4g inhibited the invasion MDA-MB-231 cells completely at 10 μM. In addition to anti-invasion property the compound 4g also inhibited the migration of LM8G7 and human ovarian cancer cells (OVSAHO) dose-dependently. Compound 4g inhibited the proliferation of LM8G7, OVSAHO, human breast cancer cells (MCF-7) and human melphalan-resistant multiple myeloma (RPMI8226-LR5) cells that are comparable to cisplatin and suramin.