Mohammad Tawkir¹*, S. A. Iqbal² and S. B. Kapoor²

¹Department of Chemistry, Arts Commerce and Science College Tukum, Chandrapur India.

²Department of Chemistry, Saifia College of Science and Education, Bhopal - 462 001 India.

Abstract

Present Communication deals with the preliminary study fo the comparison of hypoglycemic activity of two mixed sulphonyl urea. i.e. Glibenclamide (5-chloro-N-(4- N-cyclohexyl carbonyl) sulfamoyl] phenethy] 2-methoxybenzamide (L1) adn Glimeperide (3-ethyl-4-methyl-N-(4-[N-(1r,4r)-4-methylcyclohexl carbamoyl) sulfamoyl] phenethyl)-2-oxo-2, 5-dihydro-1-H-pyrrole-1-Carboxamide (L2) in equal proportion with zinc - complex of these mixed drugs result reveals that the ternary (L1ML2) complex of these drugs with zinc gives surprising results.

Keywords

Pharmacological study; Mixed ligands; metal complexes

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Copy the following to cite this article: Tawkir M*, Iqbal S. A, Kapoor S. B. Pharmacological Study of the Glibenclamide and Glimeperide Mixed Ligands and their Zinc Complexes. Biomed Pharmacol J 2010;3(1)

Copy the following to cite this URL: Tawkir M*, Iqbal S. A, Kapoor S. B. Pharmacological Study of the Glibenclamide and Glimeperide Mixed Ligands and their Zinc Complexes. Biomed Pharmacol J 2010;3(1). Available from: http://biomedpharmajournal.org/?p=1365

Introduction

In recent times zinc – insulin has been successively used as an antidabetic agent To avoid daily pricks of insulin injections. the use of oral antidabetics have increased in recent years.

It is well established fact that a compound or a complex which is to be recommended as a drug of utility must be capable of easy absorption and excretion. it is also essential that neither the substance. it self nor the metallic products there should exercise toxicity or any adverse side effect to the patient.

For this purpose it becomes imperative that following facts must be ascertained for any substance of potential to be used as a drug.

Must not product toxic effects.

Particles size must be of the order of about 5-8 microns for easy absorption.

LD50 causing 50% mortality.

Bacteriostatic tests, where necessary, such tests should be carried out on animals such as rabbit, rat and dogs, when a substance has given satisfactory results for the above tests then only it may be tried on monkeys and men.

However the oral hypoglycemic activity of Chloropropamide.tolbutamide (mixed ligands) and their copper complexes observed by lqbal et-al1 and oral hypoglycemic activity of sulphonamide isopropyl thiadiazoleobseved by janbon et-al2 was followed by hypoglycemic activity of an antibacterial compound carbutamdie by frank and fuchas3. There after Glibenclamide (1) and Glimeperide (ii) being less toxic than other sulphonylureas and were previously well recognized.

It is necessary to find out toxicity. LD50 and animal tests on the metal complex of oral antidiabetic456Iqbal and Co-workers7.8.9 have carried out preliminary pharmacological work for asessing the hypoglycemic activity of Glibenclamide and Glimeperide and compared it with its zinc complex. the results were satisfactory, the hypoglycemic activity was carried out on young dog of approximate 3.5 to 4.5 kg body weight.

Material and Methods

In present work a similar attempt have been taken by way of comparing the result of Hypoglycemic activity of mixed drugs i.e. Glibenclamide and Glimeperide compared to their zinc complex i.e. 1:1:1 (L1ML2)

Glibenclamide – Zn-Glimeperide complex synthesized and its structure was confirmed by analysis and I.R. spectroscopy.

Young dogs approximate body weight 3-4 kg were kept in laboratory conditions for three days. during this period milk and bread at 10.00 am. was given as diet and from the fourth day blood sugar was estimated at 11.00am. which indicated as a first day of the experiment.

Glibenclamide and Glimeperide 50mg (each 25mg) were given orally with small piece of chicken to the young dogs at 10.00 am. These after blood sugar was estimated at 12 pm. and 1.00 pm. The dog was kept on normal diet i.e. bread and milk for three days.

Allowing the blood sugar returning to normal after which 50mg of Glibenclamide – Zn – Glimeperide complex was given orally at 10.05 am. and the blood sugar level (BSL) estimated by ortho – toluidine method (Mono step)10.11.12 calorimetrically and the result are recorded in the table 1 and 2.

Above values were obtained after giving the Dog’s normal diet+GLB/GLP at 9.15 a.m. The dogs were kept on normal diet without drugs for three days.

Figure 1 Click here to View figure

 

Colorimetric estimation of % of blood sugar level by Glucose, GOD-POD method (Glucose oxidase – peroxidase (GOD – POD) method).

Principle

D-Glucose+O2  D-Gluconic acid +H2O2 H2O2+4-AAP+P-Hydroxy benzoic acid Sodium + H3O+   Quinone imine + 5H2O2+

Glucose in presence of GOD oxidised to form D-Gluconic acid and H2O2. Thus from react with 4-aminoantipyrine to form red quinoneimine.Quinoneimine thus forms is pink color complex the intensity of which indicates the amount of sugar present in given specimen.

Requriement

Enyzme powder buffer solution (diluent) glucose standard (100mg%)

Preparation of Glucose working solutions

Mix 1 vails of reagent to 1 in a bottle (50ml) of the reagent to diluent utility of solution in 45 days from the date of preparation.

Test procedure

Take 3 clean and dry test tube. test tube label as blank (B), Standard (S) Test (T) Blank solution is any for the selting of photo colorimeter.

Mix and incubate at 370°C for 10 min. or keep at room temperature for 20 min. Take optical density (OD) of standard and test. Using green filter against blank to set zero and absorbance of reagent blank at 270 nm.

Figure 2 Click here to View figure

 

Working	1 ml.	1ml.	1ml.
Solutions
		10µl	10µl
		Glucose	Blood
		standard	serum

 

Calculations were made using following formula

Results and Dicussion

Before the first day of taking blood sample for glucose estimation Dog’s were kept on normal diet (milk and bread)for three days. Table 2 indicates that the dogs were acclimatized for laboratory conditions with in three days and these after the blood sugar level (BSL) was daily estimated at 9.00a.m. before meals. the average values of all the five days were carried out i.e. 104, 97,4,84,6,4,87.6 mg/dl blood for five days On the day 6th GLB+GLP 50 mg was given at 9.00 a.m. and blood sugar (BSL) level were estimated at 11.10 a.m. and 1.00 pm and the results were recorded in table 2.

Table 2: Comparison of hypoglycemic activity of Glibenclamide and Glimeperide with their zinc complex

Days of taking	Drug dose	Diet	Time	Glucose estimated in mg/dl
blood sample	and time			9.00 a.m	11.00 a.m	1.00 p.m.
Day Ist	Nill	Milk & Bread	11.00 am	104	104	103
Day 2nd	Nill	Milk & Bread	11.00 am	97.4	97.5	97
Day3rd	Nill	Milk & Bread	11.00 am	84.6	85.6	85.4
Day 4th	Nill	Milk & Bread	11.00 am	82.6	82.8	82.6
Day 5th	Nill	Milk & Bread	11.00 am	87.6	87.8	87.4
Day 6th	GLB/GLP	Fasting	11.00 am	84.4	53.4*	44.7*

 

The similar process was applied to young male dogs for estimating blood sugar level (BSL) by way of giving orally GLB-Zn-GLP complex in ratio to taking 50 mg/kg body weight. Before performing the experiment of oral administration of mixed ligand complex. The animals were kept for normal diet for three days in order to maintain their normal blood sugar level (BSL).

Above values were obtained after giving the Dog’s normal diet+GLB/GLP  at 9.15 a.m. The dogs were kept on normal diet without drugs for three days

Days 10th       GLB-Zn-GLB complex 50mg                fasting           11.00 a.m.         86.2          51.4       42.8

Acknowldegements

The author are thankful to Dr. S.A. iqbal Head of department of chemistry Saifia College Bhopal, Thankful to Dr. M.M. Wankhede, Principal A.C.S. College Chandrapur for constant encouragement and providing necessary facilities.

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