Synthesis of Schiff Bases of 2-amino-5-aryl-1 , 3 , 4-thiadiazole and Its Analgesic , Anti-Inflammatory and Anti-Bacterial Activity

Schiff Bases of 2-amino-5-aryl-1,3,4-thiadiazole derivatives have been synthesized with different aromatic aldehyde. 1,3,4-thiadiazole derivatives were prepared by the reaction of thiosemicarbazide, sodium acetate and aromatic aldehyde. The structures of the titled Schiff bases were elucidated by IR and H NMR spectral measurements. All the compounds were evaluated for their analgesic activity against swiss albino mice, antiinflammatory activity against Wister albino rats. The compounds showed significant antibacterial activity against Staphylococcus aureus (gram-positive) bacteria and E. coli (gram-negative) bacteria.


Introduction
Several five membered aromatic systems having three hetero atoms at symmetrical position have been studied because of their interesting physiological properties.The derivatives of 1, 3, 4-thiadiazole was known to possess various pharmacological activities like antibacterial 1 , analgesic 2 , anti-inflammatory 3,4 , anti-convulsant 5 , antimicrobial 6 activities.Other activities that are reporting in thiadiazole containing drugs include anticancer 7 , anti-tubercular 8 , diuretic 9 and anthelmintic 10 activities.2-amino-1, 3, 4-thiadiazole are used as antitumour drugs and their acetazolamide derivatives show diuretic activity.Some of their derivatives used as carbonic anhydrase inhibitors and antiparkinsonian agents.The derivatives showed considerable promise as remedies for infection in the gastrointestinal tract.1, 3, 4thiadiazoles are also used as pesticidal, herbicidal, amoebicidal, CNS depressant, and antiviral.
The derivatives of 1, 3, 4-thiadiazoles are active against a panel of 3 cell line i.e. lung, breast and CNS cancer.They also showed good cytotoxicity against SI leukaemia and SF-268 CNS cancer.2-5-Dimercapto-1, 3, 4-thiadiazoles such as corrosion inhibition, vulcanization acceleration, prevention of sunburn and darkening of photographic developers are recorded in the patient literature.The derivatives of 1,3,4-thiadiazoles were tested for their cytotoxic potential using A549 (lung adrenocarcinoma) cells in the presence of fetal bovine serum.
In view of the above mentioned fact we synthesized biologically important heterocyclic compounds.We are describing synthesis of Schiff bases of 1, 3, 4-thiadiazoles derivatives and evaluation of their analgesic, anti-inflammatory and antibacterial activity.Their synthesis are outlined in scheme 1.The structures of the compounds were established on the basis of their IR and 1H NMR spectral data.

Experimental
Melting points were determined in open capillary tubes.Purity of the compounds were checked by TLC (Thin layer Chromatography) on silica gel plates and spots were visualized by exposure to iodine vapours.IR spectra (KBr, cm-1) were recorded on Perkins Elmer Infrared-283 FTIR.1H NMR (CDCl3) on a Bruker 300MHz spectrometer using TMS as an internal reference (chemical shift inppm).The physical data of the compounds prepared are presented in Table 1.  1.

Antimicrobial activity
The synthesized compounds were evaluated for their antibacterial activity against bacterial strain S. aureus (Gram +ve) and E. coli (Gram -ve) by cup plate diffusion method at 1000, 500, 250 µg/mL concentration.Ofloxacin were used as standard drugs for antibacterial activity.The minimal inhibitory concentration (MICs, µg/mL) of the tested compounds are recorded in Table 2 and 3.

Analgesic activity
The synthesized compounds were evaluated for their analgesic activity in swiss albino mice by using hot plate method using Pentazocine as standard drug.

Anti-inflammatory Activity
The synthesized compounds were evaluated for their anti-inflammatory activity in Wister albino rats by Carrageenan induced paw edema method using Indomethacin as standard drug.

Conclusion
A total of l0 compounds were synthesized with good yields.All synthesized compounds exhibited analgesic, anti-inflammatory and antibacterial activity.The compound 4a, 4b, 4c and 4e were shown significant analgesic activity against swiss albino mice.The compounds which shown good anti-inflammatory activity against Wister albino rats were compounds 4b, 4c, 4f and 4j.
The synthesized compounds were screened in-vitro anti-bacterial against S. aureus Gram (+ve) and E. coli Gram (-ve) bacteria which is common for most of the diseases.Few compounds like compounds 4a, 4d, 4e and 4j were shows good anti-bacterial activity against S. aureus Gram (+ve) and compounds 4b, 4d, 4e and 4j were shows good anti-bacterial activity against E. coli Gram (-ve) bacteria.Further explored of the all the compounds 4c, 4e and 4j were shown comparatively significant activity.

Table 1 .
Characterization 8-10 ml of water and 0.5 gm of aldehyde was added slowly with continuous stirring.The mixture was turbid so added methanol untill clear solution obtained shake mixture for few minutes and allowed to stand.Thiosemicarbazone precipitated from the cold solution.Filter off the precipitate and recrystallize with ethanol.2a IR (KBr) 3290(C-H), 1157(C-C),