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

doi:10.1016/j.bmcl.2009.05.110

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

Oncology

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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 language	English (US)
Pages (from-to)	4204-4206
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2009.05.110
State	Published - Aug 1 2009

Keywords

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

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bmcl.2009.05.110

Cite this

@article{f83f2f5f7e44477a9ef440d1aa9a94c8,

title = "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.",

keywords = "Hypoxia agent, Hypoxia inducing factor (HIF)-alpha, Oxazine, PET agent",

author = "Das, {Bhaskar C.} and Madhukumar, {Ankanahlli V.} and Jaime Anguiano and Sridhar Mani",

year = "2009",

month = aug,

day = "1",

doi = "10.1016/j.bmcl.2009.05.110",

language = "English (US)",

volume = "19",

pages = "4204--4206",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "15",

}

TY - JOUR

T1 - Design, synthesis and biological evaluation of 2H-benzo[b][1,4] oxazine derivatives as hypoxia targeted compounds for cancer therapeutics

AU - Das, Bhaskar C.

AU - Madhukumar, Ankanahlli V.

AU - Anguiano, Jaime

AU - Mani, Sridhar

PY - 2009/8/1

Y1 - 2009/8/1

N2 - 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.

AB - 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.

KW - Hypoxia agent

KW - Hypoxia inducing factor (HIF)-alpha

KW - Oxazine

KW - PET agent

UR - http://www.scopus.com/inward/record.url?scp=67649949954&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649949954&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2009.05.110

DO - 10.1016/j.bmcl.2009.05.110

M3 - Article

C2 - 19515559

AN - SCOPUS:67649949954

SN - 0960-894X

VL - 19

SP - 4204

EP - 4206

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 15

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this