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Potential Antioxidant Activity of New Tetracyclic and Pentacyclic Nonlinear Phenothiazine Derivatives.

Engwa GA, Ayuk EL, Igbojekwe BU, Unaegbu M - Biochem Res Int (2016)

Bottom Line: The synthesized phenothiazine derivatives exhibited reducing power potential to convert Fe(3+) to Fe(2+) and high ability to scavenge H2O2 free radical in vitro.The catalase activity significantly increased (p < 0.05) in groups 1 and 2 animals that received the phenothiazine derivatives compared to the controls (groups 3 and 4) suggesting the ability of the phenothiazine derivatives to scavenge H2O2 in vivo.The results suggest that phenothiazine derivatives, especially 6-chloro-11-azabenzo[a]phenothiazine-5-one, possess antioxidant activity though 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one was slightly toxic.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry, Chemical Sciences Department, Godfrey Okoye University, PMB 01014, Thinkers Corner, Enugu, Nigeria.

ABSTRACT
The global increase in oxidative stress related diseases such as cancer, cardiovascular, and inflammatory diseases caused by overwhelming level of free radicals in the body has encouraged the search for new antioxidant agents. Based on the ability of newly synthesized phenothiazine derivatives (6-chloro-11-azabenzo[a]phenothiazine-5-one and 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one) to oxidize H2O2, a known free radical to sulfoxide, this study assessed the in vitro and in vivo antioxidant activity. The synthesized phenothiazine derivatives exhibited reducing power potential to convert Fe(3+) to Fe(2+) and high ability to scavenge H2O2 free radical in vitro. These activities were comparable to ascorbic acid, a standard antioxidant. The catalase activity significantly increased (p < 0.05) in groups 1 and 2 animals that received the phenothiazine derivatives compared to the controls (groups 3 and 4) suggesting the ability of the phenothiazine derivatives to scavenge H2O2 in vivo. The malondialdehyde level in groups 1 and 2 animals was lower than that in group 3 that received the reference compound (ascorbic acid) and group 4 that received the solvent suggesting the ability of the phenothiazine derivatives to prevent lipid membrane damage. AST and bilirubin levels were higher in group 2 animals which received 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one compared to group 3, the positive control. The results suggest that phenothiazine derivatives, especially 6-chloro-11-azabenzo[a]phenothiazine-5-one, possess antioxidant activity though 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one was slightly toxic. This activity may be due to the presence of electron donors such as sulfur as well as the richness of hydrogen in the additional benzene rings for substitution. Further study is needed to identify tolerable doses for possible therapeutic purposes.

No MeSH data available.


Related in: MedlinePlus

Malondialdehyde (MDA) level in various animal groups.
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fig5: Malondialdehyde (MDA) level in various animal groups.

Mentions: Malondialdehyde (MDA) is one of several low-molecular weight products formed via the decomposition of certain primary and secondary lipid peroxidation products during cell membrane damage [48]. At low pH and elevated temperature, MDA reacts with 2-thiobartituric acid (TBA), generating a red fluorescent with 1 : 2 MDA : TBA adduct. The amount of MDA in groups 1 and 2 animals that received phenothiazine derivatives was lower than in group 3 that received the reference compound (ascorbic acid) and group 4 that received the solvent. The amount of MDA formed was lowest in group 1 animals given 6-chloro-11-azabenzo[a]phenothiazine-5-one (Figure 5). This result suggests that these phenothiazine compounds can prevent or minimize lipid peroxidation or cell damaged caused by free radicals. Similarly, tetracyclic NH-azaphenothiazines were shown to exhibit significant antioxidant activity to inhibit lipid peroxidation in vitro which was suggested to be due to substitution of H, Cl, and OCH3 on the benzene ring [49]. Thus, in this study, the decrease in in vivo lipidic peroxidation may be due to the additional benzene rings of the newly synthesized phenothiazine derivatives which promoted substitutions.


Potential Antioxidant Activity of New Tetracyclic and Pentacyclic Nonlinear Phenothiazine Derivatives.

Engwa GA, Ayuk EL, Igbojekwe BU, Unaegbu M - Biochem Res Int (2016)

Malondialdehyde (MDA) level in various animal groups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834405&req=5

fig5: Malondialdehyde (MDA) level in various animal groups.
Mentions: Malondialdehyde (MDA) is one of several low-molecular weight products formed via the decomposition of certain primary and secondary lipid peroxidation products during cell membrane damage [48]. At low pH and elevated temperature, MDA reacts with 2-thiobartituric acid (TBA), generating a red fluorescent with 1 : 2 MDA : TBA adduct. The amount of MDA in groups 1 and 2 animals that received phenothiazine derivatives was lower than in group 3 that received the reference compound (ascorbic acid) and group 4 that received the solvent. The amount of MDA formed was lowest in group 1 animals given 6-chloro-11-azabenzo[a]phenothiazine-5-one (Figure 5). This result suggests that these phenothiazine compounds can prevent or minimize lipid peroxidation or cell damaged caused by free radicals. Similarly, tetracyclic NH-azaphenothiazines were shown to exhibit significant antioxidant activity to inhibit lipid peroxidation in vitro which was suggested to be due to substitution of H, Cl, and OCH3 on the benzene ring [49]. Thus, in this study, the decrease in in vivo lipidic peroxidation may be due to the additional benzene rings of the newly synthesized phenothiazine derivatives which promoted substitutions.

Bottom Line: The synthesized phenothiazine derivatives exhibited reducing power potential to convert Fe(3+) to Fe(2+) and high ability to scavenge H2O2 free radical in vitro.The catalase activity significantly increased (p < 0.05) in groups 1 and 2 animals that received the phenothiazine derivatives compared to the controls (groups 3 and 4) suggesting the ability of the phenothiazine derivatives to scavenge H2O2 in vivo.The results suggest that phenothiazine derivatives, especially 6-chloro-11-azabenzo[a]phenothiazine-5-one, possess antioxidant activity though 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one was slightly toxic.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry, Chemical Sciences Department, Godfrey Okoye University, PMB 01014, Thinkers Corner, Enugu, Nigeria.

ABSTRACT
The global increase in oxidative stress related diseases such as cancer, cardiovascular, and inflammatory diseases caused by overwhelming level of free radicals in the body has encouraged the search for new antioxidant agents. Based on the ability of newly synthesized phenothiazine derivatives (6-chloro-11-azabenzo[a]phenothiazine-5-one and 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one) to oxidize H2O2, a known free radical to sulfoxide, this study assessed the in vitro and in vivo antioxidant activity. The synthesized phenothiazine derivatives exhibited reducing power potential to convert Fe(3+) to Fe(2+) and high ability to scavenge H2O2 free radical in vitro. These activities were comparable to ascorbic acid, a standard antioxidant. The catalase activity significantly increased (p < 0.05) in groups 1 and 2 animals that received the phenothiazine derivatives compared to the controls (groups 3 and 4) suggesting the ability of the phenothiazine derivatives to scavenge H2O2 in vivo. The malondialdehyde level in groups 1 and 2 animals was lower than that in group 3 that received the reference compound (ascorbic acid) and group 4 that received the solvent suggesting the ability of the phenothiazine derivatives to prevent lipid membrane damage. AST and bilirubin levels were higher in group 2 animals which received 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one compared to group 3, the positive control. The results suggest that phenothiazine derivatives, especially 6-chloro-11-azabenzo[a]phenothiazine-5-one, possess antioxidant activity though 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one was slightly toxic. This activity may be due to the presence of electron donors such as sulfur as well as the richness of hydrogen in the additional benzene rings for substitution. Further study is needed to identify tolerable doses for possible therapeutic purposes.

No MeSH data available.


Related in: MedlinePlus