PMID- 23370301
OWN - NLM
STAT- MEDLINE
DCOM- 20130920
LR  - 20130329
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 15
IP  - 3
DP  - 2013 Mar
TI  - Anti-inflammatory activity of a naphthyridine derivative 
      (7-chloro-6-fluoro-N-(2-hydroxy-3-oxo-1-phenyl-3-(phenylamino)propyl)-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide) 
      possessing in vitro anticancer potential.
PG  - 606-13
LID - S1567-5769(13)00027-1 [pii]
LID - 10.1016/j.intimp.2013.01.011 [doi]
AB  - We have previously synthesized a series of 1,8-naphthyridine-3-carboxamide 
      derivatives to identify potential anti-cancer/anti-inflammatory compounds. Three 
      derivatives, 
      7-chloro-N-(3-(cyclopentylamino)-3-oxo-1-phenylpropyl)-6-fluoro-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide 
      (C-22), 
      7-chloro-N-(2-hydroxy-3-oxo-1-phenyl-3-(phenylamino)propyl)-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide 
      (C-31) and 
      7-chloro-6-fluoro-N-(2-hydroxy-3-oxo-1-phenyl-3-(phenylamino)propyl)-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide 
      (C-34) demonstrated high cytotoxicity against a number of cancer cell lines and 
      inhibited secretion of IL-1-beta and IL-6. In the present study, C-22, C-31 and C-34 
      were assessed for modulation of pro-inflammatory cytokines, TNF-alpha and IL-8, 
      chemokine RANTES and NO produced by lipopolysaccharide (LPS)-treated mouse 
      Dendritic cells (DCs). Among the 3 compounds, C-34 showed the most potent 
      inhibition of inflammatory markers in DC model at 0.2 and 2 muM. C-34 also 
      significantly downregulated the secretion of TNF-alpha, IL-1-beta and IL-6 by murine 
      splenocytes and THP-1 cells against LPS induced levels. In vitro effects of C-34 
      on bone marrow toxicity were assessed in CFU-GM assay. Human CFU-GM population 
      was comparatively more sensitive to C-34 (0.1-10 muM) than murine CFU-GM. IC50 
      values for murine and human CFU-GM were not attained. C-34 was further examined 
      for in vivo suppression of LPS induced cytokines in a mice model. At doses 
      ranging from 1.25 to 5 mg/kg, C-34 led to significant inhibition of TNF-alpha, 
      IL-1-beta, IL-6 and MIP-1-alpha. At the highest dose of 5 mg/kg, C-34 also protected 
      LPS-treated mice against endotoxin-induced lethality. In conclusion, C-34 
      demonstrates anti-inflammatory activity in vitro and in vivo in addition to 
      cytotoxic properties. This finding suggests its potential for further development 
      as a synthetic naphthyridine derivative with dual anti-cancer and 
      anti-inflammatory (cytokine inhibition) properties.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Madaan, Alka
AU  - Madaan A
AD  - Cell Biology Lab, Dabur Research Foundation, 22, Site IV, Sahibabad, Ghaziabad, 
      Uttar Pradesh-201010, India. alka.madaan@daburresearch.in
FAU - Kumar, Vivek
AU  - Kumar V
FAU - Verma, Ritu
AU  - Verma R
FAU - Singh, Anu T
AU  - Singh AT
FAU - Jain, S K
AU  - Jain SK
FAU - Jaggi, Manu
AU  - Jaggi M
LA  - eng
PT  - Journal Article
DEP - 20130129
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 
      (7-chloro-6-fluoro-N-(2-hydroxy-3-oxo-1-phenyl-3-(phenylamino)propyl)-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Naphthyridines)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/chemical 
      synthesis
MH  - Antineoplastic Agents/*administration & dosage/chemical synthesis
MH  - Bone Marrow Cells/drug effects/pathology
MH  - Cell Line
MH  - Cytokines/genetics/*metabolism
MH  - Dendritic Cells/*drug effects/immunology
MH  - Female
MH  - Hematopoietic Stem Cells/drug effects
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Lipopolysaccharides/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Naphthyridines/*administration & dosage/chemical synthesis
EDAT- 2013/02/02 06:00
MHDA- 2013/09/21 06:00
CRDT- 2013/02/02 06:00
PHST- 2012/10/27 00:00 [received]
PHST- 2013/01/14 00:00 [revised]
PHST- 2013/01/14 00:00 [accepted]
PHST- 2013/02/02 06:00 [entrez]
PHST- 2013/02/02 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
AID - S1567-5769(13)00027-1 [pii]
AID - 10.1016/j.intimp.2013.01.011 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2013 Mar;15(3):606-13. doi: 10.1016/j.intimp.2013.01.011. 
      Epub 2013 Jan 29.