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

Bhaskar C. Das, Ankanahlli V. Madhukumar, Jaime Anguiano, Sridhar Mani

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4204-4206
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number15
DOIs
StatePublished - Aug 1 2009

Fingerprint

Oxazines
Inhibitory Concentration 50
Genes
Derivatives
Cell growth
Bioactivity
Vascular Endothelial Growth Factor A
Tumors
Assays
Neoplasms
Screening
Cells
Hep G2 Cells
Libraries
Therapeutics
Down-Regulation
Growth
oxazine 1
Hypoxia

Keywords

  • Hypoxia agent
  • Hypoxia inducing factor (HIF)-alpha
  • Oxazine
  • PET agent

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Design, synthesis and biological evaluation of 2H-benzo[b][1,4] oxazine derivatives as hypoxia targeted compounds for cancer therapeutics. / Das, Bhaskar C.; Madhukumar, Ankanahlli V.; Anguiano, Jaime; Mani, Sridhar.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 15, 01.08.2009, p. 4204-4206.

Research output: Contribution to journalArticle

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