Anti-neuroinflammatory activity of 1,5-benzodiazepine derivatives

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 13, 2010, Pages 3969-3971

  Ha, Sang Keun ^a   Shobha, Donthabhaktuni ^a,b   Moon, Eunjung ^a   Chari, Murugulla A ^a   Mukkanti, Kagga ^b   Kim, Sung Hoon ^a   Ahn, Kwang Hyun ^a   Kim, Sun Yeou ^a  

^a Kyung Hee University   (South Korea)

^b JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY   (India)

Author keywords

2,3 Dihydro 1,5 benzodiazepines; Anti neuroinflammation; Inducible NO synthase; Microglia

Indexed keywords

ANTIINFLAMMATORY AGENT; BENZODIAZEPINE DERIVATIVE; INDUCIBLE NITRIC OXIDE SYNTHASE; LIPOPOLYSACCHARIDE; NITRIC OXIDE;

ANIMAL CELL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; COMPETITIVE INHIBITION; DEGENERATIVE DISEASE; DRUG CYTOTOXICITY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; MICROGLIA; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PROTEIN EXPRESSION; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; BENZODIAZEPINES; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME ACTIVATION; LIPOPOLYSACCHARIDES; MICE; MICROGLIA; MOLECULAR STRUCTURE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE II; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES;

EID: 77954314426     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.04.133     Document Type: Article

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16. 4), which was then dried at 110 °C for 3 h.
17. 6 cells/well), and incubated in the presence or absence of different concentrations of compound 3e for a further 12 h. The amount of NO in the supernatant was detected by Griess reaction.
18. Western blot was performed to analyze iNOS expression. BV-2 cells were seeded in a 6-well plate and exposed to LPS (100 ng/ml) in the presence or absence of compound 3e for 6 h. The protein sample (40 μg for each) from the BV-2 cell extract was separated by 8% SDS-PAGE and transferred to a nitrocellulose membrane (Amersham Pharmacia Biotech, Buckinghamshire, UK). The membrane was blocked with 5% skim milk and incubated with primary antibodies (rabbit anti-iNOS; Transduction Laboratories, San Diego, CA, USA) and secondary antibodies (goat anti-rabbit IgG; Amersham Pharmacia Biotech). The blots were developed using ECL Western Blotting Detection Reagents (Amersham Pharmacia Biotech).
19. Sodium nitroprusside (SNP) was dissolved in phosphate buffered saline (PBS) at 100 mM. This SNP solution (50 μl) was mixed with 950 μl PBS containing various concentrations of compound 3e (1, 5 and 10 μM). These mixtures were incubated at 25 °C for 2.5 h, and nitrite formed through the combination of oxygen and NO released from the SNP, as measured by the Griess reaction.