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5-Chloroacetyl-2-amino-1,3-selenazoles attenuate microglial inflammatory responses through NF-kappaB inhibition.
Eur J Pharmacol 2008; 589(1-3):53-7EJ

Abstract

Microglia are the prime effector cells involved in immune and inflammatory responses in the central nervous system (CNS). In pathological conditions, microglia are activated to restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various toxic proinflammatory molecules. Thus, negative regulators of microglial activation have been identified as potential therapeutic candidates in many neurological diseases. A number of selenium-containing compounds show antioxidant activity. In this study, we investigated 2-amino-1,3-selenazole derivatives with regard to anti-inflammatory activity or inhibitory effects on microglial activation. Among 26 derivatives of 2-amino-1,3-selenazole and bis-(2-amino-5-selenazoyl) ketones, we observed that 5-chloroacetyl-2-piperidino-1,3-selenazole (CS1) and 5-chloroacetyl-2-morpholino-1,3-selenazole (CS2) strongly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) release from BV2 microglial cells. In rat primary cultured microglia, CS1 and CS2 significantly reduced LPS-induced production of NO, tumor necrosis factor (TNF)-alpha, and prostaglandin E(2). Real-time reverse transcription-polymerase chain reaction analysis revealed that the pretreatment of primary microglial cells with CS1 and CS2 attenuated LPS-induced mRNA expression for inducible NO synthase, TNF-alpha, interleukin-1beta, and cyclooxygenase-2. In addition, CS1 and CS2 suppressed LPS-induced activation of nuclear factor-kappaB and Akt. These results suggest that CS1 and CS2 may provide neuroprotection by suppressing the proinflammatory pathway in activated microglia.

Authors+Show Affiliations

Department of Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin-Si, Republic of Korea.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18538761

Citation

Nam, Kyong Nyon, et al. "5-Chloroacetyl-2-amino-1,3-selenazoles Attenuate Microglial Inflammatory Responses Through NF-kappaB Inhibition." European Journal of Pharmacology, vol. 589, no. 1-3, 2008, pp. 53-7.
Nam KN, Koketsu M, Lee EH. 5-Chloroacetyl-2-amino-1,3-selenazoles attenuate microglial inflammatory responses through NF-kappaB inhibition. Eur J Pharmacol. 2008;589(1-3):53-7.
Nam, K. N., Koketsu, M., & Lee, E. H. (2008). 5-Chloroacetyl-2-amino-1,3-selenazoles attenuate microglial inflammatory responses through NF-kappaB inhibition. European Journal of Pharmacology, 589(1-3), pp. 53-7. doi:10.1016/j.ejphar.2008.03.034.
Nam KN, Koketsu M, Lee EH. 5-Chloroacetyl-2-amino-1,3-selenazoles Attenuate Microglial Inflammatory Responses Through NF-kappaB Inhibition. Eur J Pharmacol. 2008 Jul 28;589(1-3):53-7. PubMed PMID: 18538761.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-Chloroacetyl-2-amino-1,3-selenazoles attenuate microglial inflammatory responses through NF-kappaB inhibition. AU - Nam,Kyong Nyon, AU - Koketsu,Mamoru, AU - Lee,Eunjoo H, Y1 - 2008/04/01/ PY - 2007/09/12/received PY - 2008/03/06/revised PY - 2008/03/19/accepted PY - 2008/6/10/pubmed PY - 2008/10/25/medline PY - 2008/6/10/entrez SP - 53 EP - 7 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 589 IS - 1-3 N2 - Microglia are the prime effector cells involved in immune and inflammatory responses in the central nervous system (CNS). In pathological conditions, microglia are activated to restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various toxic proinflammatory molecules. Thus, negative regulators of microglial activation have been identified as potential therapeutic candidates in many neurological diseases. A number of selenium-containing compounds show antioxidant activity. In this study, we investigated 2-amino-1,3-selenazole derivatives with regard to anti-inflammatory activity or inhibitory effects on microglial activation. Among 26 derivatives of 2-amino-1,3-selenazole and bis-(2-amino-5-selenazoyl) ketones, we observed that 5-chloroacetyl-2-piperidino-1,3-selenazole (CS1) and 5-chloroacetyl-2-morpholino-1,3-selenazole (CS2) strongly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) release from BV2 microglial cells. In rat primary cultured microglia, CS1 and CS2 significantly reduced LPS-induced production of NO, tumor necrosis factor (TNF)-alpha, and prostaglandin E(2). Real-time reverse transcription-polymerase chain reaction analysis revealed that the pretreatment of primary microglial cells with CS1 and CS2 attenuated LPS-induced mRNA expression for inducible NO synthase, TNF-alpha, interleukin-1beta, and cyclooxygenase-2. In addition, CS1 and CS2 suppressed LPS-induced activation of nuclear factor-kappaB and Akt. These results suggest that CS1 and CS2 may provide neuroprotection by suppressing the proinflammatory pathway in activated microglia. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18538761/5_Chloroacetyl_2_amino_13_selenazoles_attenuate_microglial_inflammatory_responses_through_NF_kappaB_inhibition_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00372-5 DB - PRIME DP - Unbound Medicine ER -