Design, synthesis and biological evaluation of 2H-benzo[b][1,4] oxazine derivatives as hypoxia targeted compounds for cancer therapeutics

Abstract

A small library of 2H-benzo[b][1,4] oxazine derivative was synthesized and their biological activity was tested on HepG2 cells under normoxic and hypoxic conditions. From preliminary screening, we found compound 10 and 11 specifically inhibit hypoxic cancer cell growth IC50 87 ± 1.8 μM and IC50 10 ± 3.7 μM while sparing ‘normoxic’ cells IC50 >600 M and >1 mM (not applicable), respectively. We tested the effect of 10 on MTT, clonogenic and hypoxia induced genes. The MTT correlates with clonogenic assays and most importantly compound 10 down regulates hypoxia induces genes (HIF-1α, P21 and VEGF) appropriately. We are in the process to explore the molecular mechanism of action of oxazine derivative compounds on hypoxia tumor cells.

Infrared and NMR Spectral Hammett Correlations in 4-(2-Naphthyl)-5,6-Dihydro-6-(Substituted Phenyl)-⁴H-1,3-Oxazine-2-Amines

“…In the present study, the author have investigated the effect of substituents on the infrared νNH, C=N, C-O-C (cm -1 ) stretches, 1 H NMR δNH, 13 …”

“…The infrared spectra of all oxazine imines have been recorded in SHIMADUZ Fourier Transform IR spectrophotometer using KBr disc. The NMR spectra of all compounds were recorded in BRUKER AV 400 type spectrometer, using CDCl 3 as a solvent, 400 MHz frequency was applied for recording 1 H, 100 MHz for 13 C NMR spectra, taking TMS as standard.…”

“…The assigned νNH, C=N (cm -1 ) stretches, 1 H NMR δNH, 13 C NMR δC=N (ppm) chemical shifts of 4-(2-naphthyl)-5,6-dihydro-6(substituted phenyl)- 4 H-1,3-oxazine-2-amines were presented in Table1. These data were correlated with Hammett substituent constants, F and R parameters linear regression analysis [1][2][3][4]8,[27][28][29].…”

“…The unsaturated cyclic oxazine-2-amines are important bioactive molecules. They possess many biologically activities such as antimicrobial [9], anti-plasmodial [10], anti-cancer [11], anti-depressants [12], cytotoxicity [13], anti-osteoplastic [14], anti-tumour [15], anti-oxidant [16], anti-tuberculosis [17], anti-neoplastic [18], antagonists [19], antiinflammatory [20] anti-infectants [21], IKB kinase beta [22], PTP-1B inhibition [23] and insect antifeedant activities [24].…”

Aryl Chalcones as Efficient Precursors for Deriving Oxazine: Solvent-Free Synthesis and Antimicrobial Activities of some Oxazine-2-amines

“…The important medicinal activities of these oxazines are anti-bacterial [2][3][4], anti-fungal [2][3][4], antiplasmodial [5], anti-cancer [6], anti-depressants [7], cytotoxicity [8], anti-osteoplastic [9], anti-tumour [10], anti-oxidant [11], anti-tuberculosis [12], anti-neoplastic [13], antagonists [14], anti-inflammatory [15], anti-infectants [16], IKB kinase beta [17] and PTP-1B inhibition [18].…”