A Review on Antidiabetic Activity of Substituted 1, 3, 4 –Thiadiazole Derivatives.

 

Yogesh Vaishnav*¹, Arvind Kumar Jha¹, Shekhar Verma¹, Pranita Kashyap², Chanchal Deep Kaur²

¹SSTC-SSGI-Faculty of Pharmaceutical Sciences, Bhilai,Chhattisgarh490020 India.

²ShriRawatpuraSarkar Institute of Pharmacy, Kumhari, Durg, Chhattisgarh 490042 India.

 

ABSTRACT:

1,3,4 thiadiazole is considered to be an important heterocyclic nuclei which possesses wide variety of biological activity such as anticancer, anti-inflammatory, antimicrobial, antihypertensive, antifungal, antidiuretic and antidiabetic. Modification and substitution on thiadiazole ring minimizes the toxicity with improved activity. Present review highlights the recent research findings on 1, 3, 4 thiadiazole nucleus for antidiabetic activity. The information highlighted in this review acts as important gestalt for researchers to build a novel chemical entity owning antidiabetic activity.

 

 

INTRODUCTION:

In the field of pharmaceuticals and chemical, researchers develop their interest on heterocyclic compounds and their derivatives to design newer compound with improved biological activity by modifying the heterocyclic ring. Among many other heterocyclic compounds, 1, 3, 4 thiadiazole substituted compounds were considered to be most significant in divulging various biological activities. The heterocyclic arrangement of thiadiazole consisting of dual nitrogen atoms with one atom of sulphur.1, 3, 4 thiadiazole is an isomeric form of thiadiazole among other isomers such as 1, 2, 3-4-5 thiadiazole. Aromaticity of 1, 3, 4 thiadiazole is high and considered as weak base due to the presence of sulphur atom¹

 

Antidiabetic activity of substituted 1, 3, 4 thiadiazole derivatives:

1. P. thrilochana et al.synthesized and reported following 1, 3, 4 thiadiazole derivatives as antidiabetic agents. Figure 1 shows the various substituted thiadiazole derivatives.

 

Fig.1:Substituted 1,3,4 thiadiazole derivatives

 

1.    5-(4-methoxybenzylideneamino)-1,3,4-thiadiazole-2-thio(R=p-methoxybenzaldehyde)

2.    5-(4-(dimethylamino) benzylideneamino)-1,3,4- thiadiazole-2-thiol(R=p-di methyl amino benzaldehyde

3.    5-(4-nitrobenzylideneamino)-1,3,4-thiadiazole- 2-thiol(R=p-nitrobenzaldehyde)

4.    5-(3,4-dimethoxybenzylideneamino)-1,3,4thiadiazole-2-thiol(R=3,4dimethoxybenzaldehyde)

5.    5-(4-chlorobenzylideneamino)-1,3,4-thiadiazole- 2-thiol(R=p-chlorobenzaldehyde)

6.    5-(4-bromobenzylideneamino)-1,3,4-thiadiazole- 2-thiol(R=p-bromobenzaldehyde)

 

The researchers compared the synthesized compounds with standard marketed drug glibenclamide and concluded that the introduction of imine substitution in thiadiazole nucleus revealed sensible antidiabetic activity. Evaluation of antidiabetic activity of synthesized compounds was carried out by using alloxan induced model²

 

2. Prasanna A Datar and Tejashree A Deokule design and synthesized thiadiazole compounds as antidiabetic agent using docking studies.The promising synthesized compound was shown in figure 2. Theresearchers develop and synthesized twenty five compounds out of which only one compound “2-(5-phenyl-1,3,4- thiadiazol-2-ylamino)-N-ptolylacetamide” showed the significant antidiabetic activity. Antidiabeticactivities of synthesized compounds were done by the help of alloxan induced diabetes rat model³.

 

Figure 2:2-(5-phenyl-1, 3, 4-thiadiazol-2-ylamino)-N-ptolylacetamide

 

3.Shashikant R Pattan et al synthesized and reported different substituted 1,3,4 thiadiazole derivatives in which one of the compound  2-(5-(4-nitrophenyl)-1,3,4-thiadiazol-2-ylamino)-1-(piperidin-1-yl)ethanone  was evaluated as a potent  antidiabetic agent. Synthesized compounds were evaluated and compared by standard drug glibenclamide also using Wister albino rat by alloxan induced tail tipping method. Figure 3 shows the potent antidiabetic drug synthesized by researchers⁴

 

Figure 3:2-(5-(4-nitrophenyl)-1, 3, 4-thiadiazol-2-ylamino)-1-(piperidin-1-yl)ethanone

 

4.CompoundN-Ethyl-5 Phenyl-1, 3, 4 thiadiazol-2-amine was synthesized and evaluated for antidiabetic activity by Mhasalkar MY et al. The researchers studied that the substitution of phenyl ring at position fifth and substitution of amine group at position 2 accelerate the activity as antidiabetic⁵. The active synthesized compound was shown in figure 4.

 

Figure 4:N-Ethyl-5 Phenyl-1, 3, 4 thiadiazol-2-amine.

 

5. A novel series of 1, 3, 4 thiadiazole derivatives were synthesized by SR Pattan et al. The researchers synthesized and evaluated eighteen compounds in which four of them showed promising antidiabetic activity and few of them showed moderate activity. The antidiabetic activities were evaluated by using alloxan induced albino rat model and by tail tipping method⁶.Following compounds were reported as potent antidiabetic drugs and showed in figure 5 (a) whereas the compounds with moderate activity was shown in figure 5(b).

 

Potent activity.

 

Figure 5(a)

 

Moderate  activity.

 

Figure 5(b)

 

6. A new series of 2 amino-5 alkyl 1, 3, 4 thiadiazole derivatives (Fig.6) as hypoglycemic agents were synthesized by Francis L Chubb and Jacqueline Nissenbaum. The researchers studied that substitution of alkyl group at position 5 and substitution of amino group at position 2 in 1,3,4 thiadiazole nucleus increases the antidiabetic activity⁷.

 

Figure 6: 2 amino-5 alkyl 1, 3, 4 thiadiazole

7. M. SaiHarika et al. analyzed different derivatives of 2-phenyl-3-(5-phenyl-1, 3, 4-thiadiazol-2-yl)-1, 3-thiazolidin-4-one (Figure 7) as antidiabetic agents. All the compounds were evaluated for antidiabetic activity by alloxan induced diabetic Wister albino rat. Researchers showed that substituted 1, 3, 4 thiadiazole benzaldehyde derivatives possesses promising antidiabetic activity⁸.

 

Figure 7:Substituted 1, 3, 4 thiadiazole benzaldehyde derivatives

 

8. Ashwin U. Rao et al design and discovered an innovative series of 2-piperidinopiperidine thiadiazoles as antidiabetic agents. The researchers developed 21 compounds in which one of the compound 4-(5-([1,4-bipiperidin]-1-yl)-1,3,4-thiadiazol-2-yl)-2-(pyridine-2-yl)morpholine showed potent antidiabetic activity and is shown in fig 8.The whole synthesized compounds were evaluated as antidiabetic agents by using STZ diet induced obesity type 2 diabetic mice⁹.

 

Figure 8: 4-(5-([1,4-bipiperidin]-1-yl)-1,3,4-thiadiazol-2-yl)-2-(pyridine-2-yl)morpholine.

 

CONCLUSION:

1,3,4 thiadiazolecomprises of two carbon atoms which are deficient in electron with dual nitrogen atoms and a single sulphur atom having lone pairs of electron. The structural arrangement of 1, 3, 4 thiadiazole make it electron deficient, provide aromaticity and gives high thermotic stability. It is observed that substitution on position three and in position five can activate the thiadiazole ring highly. Nitrogen atoms present in the 1, 3, 4 thiadiazole ring have a tendency to nucleophilic attack whereas the carbon atom can suffer by both electrophilic and nucleophilic attack.1,3,4 thiadiazole consist of firm scaffold assembly on which different substitution can give favorable results. The researchers can assume further developments of 1, 3, 4- thiadiazole template in drug design and discovery. Additionally antidiabetic activity of substituted 1, 3, 4 thiadiazole ring can be exaggerated by carrying out further studies on its possible substitutions to design and synthesize potent agents. This review article may provide platform to researchers to develop a potent antidiabetic agent consisting 1,3,4 thiadiazole nucleus.

 

CONFLICT OF INTEREST:

The authors confirm that this review article content has no conflict of interest.

 

ACKNOWLEDGEMENTS:

Authors are grateful to the Shri Rawatpura Sarkar Institute Of Pharmacy, Kumhari, Durg, for providing necessary facilities.

 

REFERENCES:

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Accepted on 29.10.2017        © RJPT All right reserved

Research J. Pharm. and Tech 2017; 10(12): 4467-4470.