Modulation of diorganoyl dichalcogenides reactivity by non-bonded nitrogen interactions.
The study was designed to explore the biochemical influence of non bonding nitrogen interactions (N⋯Se/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 N⋯Se interaction but also for the first time the effect of non bonded N⋯S 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 α-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.
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil. waseem_anw@yahoo.com
Waseem
W
Hassan
Senthil
S
Narayanaperumal
Kashif
K
Gul
Ata Ur
AU
Rahman
Antonio L
AL
Braga
Oscar E D
OE
Rodrigues
João Batista Teixeira
JB
Rocha
D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism; D003855:Deoxyribose / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009584:Nitrogen / Q000378:metabolism*; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010851:Picrates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D001713:Biphenyl Compounds; D005609:Free Radicals; D016566:Organoselenium Compounds; D010851:Picrates; D013440:Sulfides; D017392:Thiobarbituric Acid Reactive Substances; D003855:Deoxyribose; C004931:1,1-diphenyl-2-picrylhydrazyl; D009584:Nitrogen