Exploring the anti-inflammatory activity of a novel 2-phenylquinazoline analog with protection against inflammatory injury

Journal Article · Mon Oct 15 04:00:00 EDT 2012 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2012.07.032· OSTI ID:22215937

Chatterjee, Nabanita; Das, Subhadip; Bose, Dipayan; Banerjee, Somenath; Das, Sujata ^[1]; Chattopadhyay, Debprasad ^[2]

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1. Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700032, West Bengal (India)
2. ICMR Virus Unit, ID and BG Hospital, GB 4, 57 Dr Suresh C Banerjee Road, Beliaghata, Kolkata-700010 (India)

Inflammation is a protective immune response against harmful stimuli whose long time continuation results in host disease. Quinazolinones are nitrogen containing heterocyclic compounds with wide spectrum of biological activities. The anticancer effect of a 3-(arylideneamino)‐phenylquinazoline-4(3H)-one derivative was reported earlier. The anti-inflammatory effect of these quinazolinone derivatives has now been examined in endotoxin stimulated macrophages and in different in vivo models of inflammation by measuring the proinflammatory cytokines (TNF-α, IL-1β and IL-6), mediators NO and NF-κB (by ELISA and western blot), and translocation of the nuclear factor kB (by immunocytochemical analysis). To elucidate the in vivo effect, mice endotoxin model was and the various levels of edema, inflammatory pain and vascular permeability were studied. One of the quinazolinone derivatives showed significant anti-inflammatory activity in stimulated macrophage cells by inhibiting the expression of TNF-α, IL-1β, IL-6, iNOS, COX-2, p-IκB and NF-κBp65. Significant (P < 0.01) improvement was observed in the mortality of endotoxemic mice. The carrageenan and formalin-induced paw edema thicknesses were found to be reduced significantly (P < 0.01) along with the reduction of pain, vascular permeability and edema induced by complete Freund's adjuvant (P < 0.01). These findings indicate that 3-(arylideneamino)‐phenylquinazoline-4(3H)-one derivative as a potential anti-inflammatory agent. -- Highlights: ► 2-phenylquinazoline analog suppresses the cytokines in stimulated macrophages. ► 2-phenylquinazoline analog down regulated NF-kB P65 translocation. ► Role of 2-phenylquinazoline analog in endotoximia and peripheral inflammations.

• OSTI ID: 22215937
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 264; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIPYRETICS
EDEMA
ENZYME IMMUNOASSAY
ENZYMES
FORMALDEHYDE
HETEROCYCLIC COMPOUNDS
IN VIVO
INFLAMMATION
INJURIES
LYMPHOKINES
MACROPHAGES
MICE
MORTALITY
NITRIC OXIDE
NITROGEN
PAIN
PERMEABILITY
PHOSPHATES
PROSTAGLANDINS
RADIOPROTECTIVE SUBSTANCES
RECEPTORS
THICKNESS
TRANSLOCATION