ABSTRACT
Ethambutoldihydrogenchloride (EMB) with chemical formula C10H24N2O2.2HCl is ethane-1,2-diamine in which one hydrogen attached to each of the nitrogen is substituted by a 1-hydroxybutan-2-yl group (S,S-configuration). It is an FDA approved drug and has been used for treatment of tuberculosis since 1960's. Prolong use of EMB has a side effect of visual impairment and in literature it is related with the depletion of Zn metal from the body. As it is a good chelating agent, many metal II complexes have been synthesized with anti-tubercular activity. The purpose of this work was to synthesize metal II complexes of EMB and to evaluate their antioxidant activity along with enzyme inhibition activity (acetylcholine esterase and protease). The metals used for complex formation were Co, Zn, Fe, Cu and Ni. IR spectral data and physical parameters supported the complex formation. The obtained results showed the synthesized complexes as notable antioxidants and enzyme inhibitors.
Subject(s)
Antioxidants/pharmacology , Antitubercular Agents/pharmacology , Cholinesterase Inhibitors/pharmacology , Ethambutol/pharmacology , Protease Inhibitors/pharmacology , Acetylcholinesterase/blood , Animals , Antioxidants/chemical synthesis , Antitubercular Agents/chemical synthesis , Biphenyl Compounds/chemistry , Chlorides/chemistry , Cholinesterase Inhibitors/chemical synthesis , Dose-Response Relationship, Drug , Erythrocytes/drug effects , Erythrocytes/enzymology , Ethambutol/analogs & derivatives , Ethambutol/chemical synthesis , Ferric Compounds/chemistry , Humans , Oxidation-Reduction , Picrates/chemistry , Protease Inhibitors/chemical synthesisABSTRACT
The purpose of this study was to assess the antioxidant potential and enzyme inhibition of various fractions of Zizyphus oxyphylla. The plant metabolites were extracted in methanol and partitioned with n-hexane, chloroform, ethyl acetate and n-butanol successively. Phytochemical screening showed presence of alkaloids, terpenoids and flavonoids in ethyl acetate and n-butanol fractions. The antioxidant potential and acetylcholine esterase assay of all these fractions and remaining aqueous fraction was evaluated by using reported methods. The results revealed that chloroform soluble fraction exhibited highest percent inhibition of DPPH radical as compared to other fractions. It showed 95.01 ± 0.37% inhibition of DPPH radical at a concentration of 120 µg/mL. The IC50 of this fraction was 13.20 ± 0.27 µg/mL, relative to butylated hydroxytoluene (BHT, a reference standard), having IC50 of 12.10 ± 0.29 µg/mL. It also showed highest total antioxidant activity i.e. 1.723 ± 0.34 as well as highest FRAP value (339.5 ± 0.57 TE µm/mL) and highest total phenolic contents (142.65 ± 1.20 GAE mg/g) as compared to the other studied fractions. The fractions were also studied for Acetylcholine esterase enzyme (AChE) enzyme inhibition activity and n-butanol soluble fraction exhibited maximum inhibition (95.5 ± 0.13 mg/mL with IC50 =9.58 ± 0.08 mg/mL relative to galanthamine (13.26 ± 0.73 mg/mL), while n- hexane soluble fraction (165.15 ± 0.94 mg/mL) showed non-significant. We are still working to isolate pure compounds for active fractions targeting potent inhibition responsible for some activities.
Subject(s)
Acetylcholinesterase/metabolism , Antioxidants/pharmacology , Cholinesterase Inhibitors/pharmacology , Plant Extracts/pharmacology , Ziziphus , Antioxidants/isolation & purification , Biphenyl Compounds/chemistry , Cholinesterase Inhibitors/isolation & purification , Dose-Response Relationship, Drug , Phytotherapy , Picrates/chemistry , Plant Extracts/isolation & purification , Plants, Medicinal , Solvents/chemistry , Ziziphus/chemistryABSTRACT
The present investigation deals with the determination of various serum enzymes known to be elevated during myocardial infarction (MI) and estimation of selected metals like Cu, Cr, Co, Fe, Pb, and Mg by flame atomic absorption spectrophotometry. The data obtained thereby were processed for the determination of correlation coefficient matrix among the cardiac enzymes and the serum metals. The study evidenced the accumulation of Pb during MI and reduction in the level of Fe. A significant negative correlation was observed between Cu and creatine kinase-MB. The data were also segregated into various groups to study the influence of age and gender on the levels of selected parameters. In both the genders, the age of the patients was found to be correlated significantly with various cardiac enzymes. In case of male patients, the most significant correlation was observed between age and blood sugar at random. The other significant correlations among the male patients included Cr-CPK, Cr-creatine kinase-MB, Fe-age, and others. In female patients, the pairs of studied parameters that exhibited significant correlations included age-lactic dehydrogenase, creatine phosphokinase isoenzyme-aspartate aminotransferase, lactic dehydrogenase-creatine phosphokinase isoenzymes, Pb-Fe, and Cu-Co in addition to others.
