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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

Bilirubin level in various animal groups.
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fig7: Bilirubin level in various animal groups.

Mentions: The liver is an organ in the body that metabolises drugs or xenobiotics to enhance their activity or facilitate their elimination. However, foreign substances may have adverse effect on the liver. Chemicals that cause liver injury are called hepatotoxins or hepatotoxicants. Hepatotoxicants are exogenous compounds of clinical relevance and may include overdoses of certain medicinal drugs, industrial chemicals, natural chemicals like microcystins, herbal remedies, and dietary supplements [50, 51]. Based on the fact that the newly synthesized phenothiazine compounds are of clinical relevance and are exogenous to the body, it was necessary to evaluate their effect on the liver. Biochemical markers like alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and bilirubin have been used to assess hepatotoxicity. Elevations in the serum enzyme levels of these markers are taken as the relevant indicators of liver toxicity. From the result obtained, the AST and bilirubin levels in group 2 animals treated with 6-(4-bromophenyl)-10-methyl-11-azabenzo[a]phenothiazine-5-one were slightly higher than that of groups 3 and 1 animals that received the reference compound and 6-chloro-11-azabenzo[a]phenothiazine-5-one, respectively, and AST increase was significant (p < 0.05) compared to the controls (Figures 6 and 7). However, the ALT levels did not significantly (p > 0.05) vary in the various animal groups (Figure 8). More so, more casualties were observed in the animal group that received 6-(4-bromophenyl)-10-methyl-11-azabenzo[a]phenothiazine-5-one. This suggests that these phenothiazine derivatives, most especially 6-(4-bromophenyl)-10-methyl-11-azabenzo[a]phenothiazine-5-one, may be toxic to the body at the given administered doses.


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

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

Bilirubin level in various animal groups.
© Copyright Policy
Related In: Results  -  Collection

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

fig7: Bilirubin level in various animal groups.
Mentions: The liver is an organ in the body that metabolises drugs or xenobiotics to enhance their activity or facilitate their elimination. However, foreign substances may have adverse effect on the liver. Chemicals that cause liver injury are called hepatotoxins or hepatotoxicants. Hepatotoxicants are exogenous compounds of clinical relevance and may include overdoses of certain medicinal drugs, industrial chemicals, natural chemicals like microcystins, herbal remedies, and dietary supplements [50, 51]. Based on the fact that the newly synthesized phenothiazine compounds are of clinical relevance and are exogenous to the body, it was necessary to evaluate their effect on the liver. Biochemical markers like alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and bilirubin have been used to assess hepatotoxicity. Elevations in the serum enzyme levels of these markers are taken as the relevant indicators of liver toxicity. From the result obtained, the AST and bilirubin levels in group 2 animals treated with 6-(4-bromophenyl)-10-methyl-11-azabenzo[a]phenothiazine-5-one were slightly higher than that of groups 3 and 1 animals that received the reference compound and 6-chloro-11-azabenzo[a]phenothiazine-5-one, respectively, and AST increase was significant (p < 0.05) compared to the controls (Figures 6 and 7). However, the ALT levels did not significantly (p > 0.05) vary in the various animal groups (Figure 8). More so, more casualties were observed in the animal group that received 6-(4-bromophenyl)-10-methyl-11-azabenzo[a]phenothiazine-5-one. This suggests that these phenothiazine derivatives, most especially 6-(4-bromophenyl)-10-methyl-11-azabenzo[a]phenothiazine-5-one, may be toxic to the body at the given administered doses.

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