PMID- 22683714
OWN - NLM
STAT- MEDLINE
DCOM- 20121106
LR  - 20161125
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 199
IP  - 2
DP  - 2012 Aug 30
TI  - Modulation of diorganoyl dichalcogenides reactivity by non-bonded nitrogen 
      interactions.
PG  - 96-105
LID - 10.1016/j.cbi.2012.05.010 [doi]
AB  - The study was designed to explore the biochemical influence of non bonding 
      nitrogen interactions (Ncdots, three dots, centeredSe/S) on organochalcogens potency. Approximately five 
      and six times higher thiol peroxidase (TPx) like activity was observed for 
      compound (C)-2 than C-1 and C-3, respectively. C-2 also displayed significantly 
      (p<0.05) higher activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical 
      scavenging and deoxyribose degradation assays. All compounds, except C-4 and C-6 
      significantly inhibited Fe (II) and sodium nitroprusside (SNP) induced 
      thiobarbituric acid reactive species (TBARS) production in rat's brain, liver and 
      kidney preparations with highest activity observed for C-2. The highest C-2 
      activity was attributed to the presence of non-bonded nitrogen interactions which 
      were absent in C-1 and blocked with butoxycarbonyl (BOC group) in C-3. The same 
      structural activity analogy was extended to organosulfur compounds and it was 
      observed that compound with non-bonding nitrogen interactions, i.e. C-5 has 
      significantly (p<0.05) higher TPx like activity than C-6 and C-4. C-5 at the 
      highest tested concentration significantly (p<0.05) protected against Fe (II) and 
      SNP induced TBARS formation in rat's brain, kidney and liver preparations but did 
      not display activity in DPPH and deoxyribose degradation assays. This study 
      confirms the influence of not only Ncdots, three dots, centeredSe interaction but also for the first time 
      the effect of non bonded Ncdots, three dots, centeredS interactions on organochalcogens potency. C-2 (with 
      the highest activity) was also tested in vivo and was administered at three 
      different doses, i.e. 15, 30 and 50 mg/kg to get an exact idea about its 
      interaction with thiol containing molecules (NPSH) and enzyme alpha-ALA-D (sulfhydryl 
      containing enzyme). Oxidative stress parameters, i.e. free radical concentration 
      by dichlorofluoreseein (DCF) assay, TBARS, ascorbic acid level, hepatic (ALT and 
      AST) and renal (urea and creatinine) toxicity markers were also estimated to get 
      an insight about its possible toxicological profile. Our data indicates that C-2 
      has higher TPx and Antioxidant activity and importantly, C2 did not induce 
      toxicity even when tested at relatively high doses, indicating that its 
      pharmacological properties should be further explored in models of diseases 
      associated with oxidative stress.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Hassan, Waseem
AU  - Hassan W
AD  - Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade 
      Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil. 
      waseem_anw@yahoo.com
FAU - Narayanaperumal, Senthil
AU  - Narayanaperumal S
FAU - Gul, Kashif
AU  - Gul K
FAU - Rahman, Ata Ur
AU  - Rahman AU
FAU - Braga, Antonio L
AU  - Braga AL
FAU - Rodrigues, Oscar E D
AU  - Rodrigues OE
FAU - Rocha, Joao Batista Teixeira
AU  - Rocha JB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120605
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Antioxidants)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Free Radicals)
RN  - 0 (Organoselenium Compounds)
RN  - 0 (Picrates)
RN  - 0 (Sulfides)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 533-67-5 (Deoxyribose)
RN  - DFD3H4VGDH (1,1-diphenyl-2-picrylhydrazyl)
RN  - N762921K75 (Nitrogen)
SB  - IM
MH  - Animals
MH  - Antioxidants/*chemistry/*pharmacology
MH  - Biphenyl Compounds/metabolism
MH  - Deoxyribose/metabolism
MH  - Free Radicals/metabolism
MH  - Kidney/drug effects/metabolism
MH  - Lipid Peroxidation/drug effects
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - Nitrogen/*metabolism
MH  - Organoselenium Compounds/*chemistry/*pharmacology
MH  - Oxidative Stress/*drug effects
MH  - Picrates/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Sulfides/chemistry/pharmacology
MH  - Thiobarbituric Acid Reactive Substances/metabolism
EDAT- 2012/06/12 06:00
MHDA- 2012/11/07 06:00
CRDT- 2012/06/12 06:00
PHST- 2012/04/06 00:00 [received]
PHST- 2012/05/01 00:00 [revised]
PHST- 2012/05/28 00:00 [accepted]
PHST- 2012/06/12 06:00 [entrez]
PHST- 2012/06/12 06:00 [pubmed]
PHST- 2012/11/07 06:00 [medline]
AID - S0009-2797(12)00098-1 [pii]
AID - 10.1016/j.cbi.2012.05.010 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2012 Aug 30;199(2):96-105. doi: 10.1016/j.cbi.2012.05.010. 
      Epub 2012 Jun 5.