Investigation of antioxidant properties of some 6-(α-aminobenzyl)thiazolo[3,2-b]-1,2,4-triazole-5-ol compounds

Figures & data

Table I.  The structures of 6-(α-aminobenzyl)thiazolo[3,2-b]-1,2,4-triazole-5-ols and their antiinflammatory activities and ulcer scores [8,9].

Compounds (Antiinflammatory activity, % inh.)	Ulcer incidence	R	R′	R″
Ia (66%) [9]	2/4	–CH3	3,4,5-t-OCH3
Ib (41%) [9]	0/4	–CH3	3,4,5-t-OCH3
Ic (52%) [8]	6/8	–CH3	3-NO2
Id (63%) [8]	5/8	3–NO2C6H4–	–H

Table II.  Effects of the test compounds administered by a gastric tube (for 3 days) on lipid peroxidation (as mean±SEM nmol TBARS/g wet weight) levels in stomach, liver and kidney tissues of mice.

Compounds (n = 4-6)	Dose mg/kg	Stomach	Liver	Kidney
Control		67.3 ± 3.8	182.8 ± 7.1	138.2 ± 3.8
Ia	20	73.4 ± 5.7	173.9 ± 4.3	168.5 ± 3.9
Ib	20	62.8 ± 2.9	212.8 ± 6.5	175.6 ± 7.2
Ic	50	62.7 ± 2.9	212.6 ± 12.0	323.9 ± 13.7 ***
Id	50	213.1 ± 18.0 ***	251.7 ± 9.9 *	148.0 ± 3.2
Indomethacin	10	127.1 ± 6.9 ***	315.0 ± 12.8***	147.0 ± 3.8

* p < 0.05; ** p < 0.01;*** p < 0.001.

Table III.  Effects of the synthesized compounds on the alteration of TBARS, T-SH and GSH in ethanol-induced oxidative stress in mouse stomach.

Groups (n = 5)	TBARS	T-SH (μmol/g wet wt.)	GSH (μmol/g wet wt.)
Control	64.4 ± 4.6	168.7 ± 0.7	24.1 ± 1.5
EtOH^a	130.9 ± 5.2 ***	116.7 ± 1.2**	6.0 ± 0.5 ***
Ia + EtOH^b	122.7 ± 9.7	129.9 ± 2.9**	12.2 ± 0.8***
Ib + EtOH^b	121.8 ± 5.9	117.9 ± 1.9	9.8 ± 0.4*
Indo + EtOH^b	167.2 ± 2.3**	119.3 ± 3.2	2.7 ± 0.5*

EtOH, ethanol; Indo, indomethacin. a: compare to the control group; b: compare to the EtOH group. * p < 0.05; ** p < 0.01; ***p < 0.001.

Table IV.  Effects of the synthesized compounds on the alteration of TBARS; T-SH and GSH levels in ethanol-induced oxidative stress in mouse liver.

Groups (n = 5)	TBARS (nmol/g wet wt.)	T-SH (μmol/g wet wt.)	GSH (μmol/g wet wt.)
Control	220.5 ± 4.7	324.6 ± 7.2	38.6 ± 1.6
EtOH^a	309.6 ± 6.6***	179.6 ± 11.2***	10.9 ± 0.3 ***
Ia + EtOH^b	233.5 ± 9.3***	290.4 ± 13.5***	18.3 ± 0.7***
Ib + EtOH^b	267.1 ± 10.4*	265.9 ± 10.9***	15.0 ± 0.7*
Indo + EtOH^b	315.4 ± 9.4	216.9 ± 13.2	7.4 ± 0.9

EtOH, ethanol; Indo, indomethacin. a: compare to the control group; b: compare to the EtOH group. * p < 0.05; ** p < 0.01; ***p < 0.001.

Table V.  Effects of the synthesized compounds on the alteration of TBARS, T-SH and GSH levels in ethanol-induced oxidative stress in mouse kidney.

Groups (n = 5)	TBARS (nmol/g wet wt.)	T-SH (μmol/g wet wt.)	GSH (μmol/g wet wt.)
Control	146.1 ± 5.9	131.4 ± 0.4	21.9 ± 1.0
EtOH^a	164.7 ± 2.6	129.8 ± 2.1	18.7 ± 0.6*
Ia + EtOH^b	147.3 ± 9.6	126.3 ± 2.6	19.2 ± 0.7
Ib + EtOH^b	187.6 ± 17.6	122.8 ± 1.2	16.6 ± 0.4
Indo + EtOH^b	214.6 ± 10.9*	109.9 ± 2.1***	3.1 ± 0.3***

EtOH, ethanol; Indo, indomethacin. a: compare to the control group; b: compare to the EtOH group. * p < 0.05; ** p < 0.01; ***p < 0.001.

Table VI.  COX inhibitory activity of the compound Ib and IC₅₀ values for the reference compounds.

Test compound	COX-1 inhibition (%)^*, 10 μM	COX-2 inhibition (%)^*, 10 μM
Ib	–	17
Reference compounds	IC50 (μM)	(nH)
Diclofenac	0.015	(0.6)
NS 398	0.34	(1.2)

* For the test compound, the result is expressed as a percent inhibition of control activity. The symbol (–) indicates an inhibition of less than 10%. IC₅₀ values and Hill coefficients (nH) were determined by non-linear regression analysis of the inhibition curves. These parameters were obtained by Hill equation curve fitting.

Table

Assay	Substrate/Stimulus	Incubation	Reaction product	Method of detection
COX-1 (h)	AA (0.3 μM)	15 min./37°C	PGE2	RIA
COX-2 (h)	PMA (100 nM)	20 h/37°C	PGE2	RIA
(Whole cells-activity) for COX-2 induction
	AA (50 μM)	30 min./37°C
	for COX-2 activity

Abbreviations: AA: arachidonic acid; COX: cyclooxygenase; HUVEC: human umbilical vein endothelial cells; PGE₂: prostaglandin E₂; PMA: phorbol 1,2-myristate 13-acetate.

B Tozkoparan, GA Kılcıgil, R Ertan, M Ertan, P Kelicen, R Demirdamar. Synthesis and evaluation of antiinflammatory activity of some thiazolo[3,2-b]-1,2,4-triazole-5(6h)-ones and their michael addition products. Arzneim. Forsch/Drug Res 1999;49 (II):1006–1011.

 PubMedGoogle Scholar

B Tozkoparan, G Aktay, E Yeşilada, M Ertan. Synthesis of some thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones and their novel Michael addition products with antiinflammatory activity. Arzneim Forsch/Drug Res 2001;51 (I):470–477.

 PubMedGoogle Scholar