Synthesis, characterization and biological evaluation of some novel N-Mannich bases of heterocyclic 1,3,4-thiadiazole.

Abstract

A series of some novel N-Mannich bases of heterocyclic 1,3,4-thiadiazole were synthesized through the condensation reaction of 1,3,4-thiadiazole containing a aromatic secondary amine, aromatic aldehydes and cyclic compounds employing Mannich reaction and using conventional synthesis. All the synthesized compounds were obtained in the range of 57.41-83.3 % yield. The structures of synthesized compounds were confirmed by UV, IR, 1H NMR spectroscopy. the essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore. The in vitro antibacterial activity of the synthesized compounds was determined, against two Gram-positive bacteria, viz. S. aureus & B. subtilis and Gram-negative, viz. E. coli and K. pneumoniae, by cup-plate method using the standard drug ciprofloxacin. Minimum inhibitory concentrations (MIC) changed in the range of 1.56_ _ 200 mg mL_1. Compound 3b exhibited excellent activity against both bacteria. The in vitro antifungal activity of the synthesized compound was also evaluated by cup-plate method against the fungi A. niger and C. albicans compared with the standard drug Fluconazole. Compound 4a, 8a exhibited excellent activity against both fungi. The result has shown that the compounds are quite active against pathogens under study and were nontoxic. The anti-inflammatory activity of the compound was evaluated, on albino rats, by carageenan induced rat paw oedema method using the standard drug diclofenac sodium. Compound 7b and 8c exhibited excellent anti-inflammatory and analgesic pharmacological activities. Structurally the compound 7b has a greater number of unsaturated hydrocarbons in schiff base, which shows good lipophilic properties within electron rich morpholine ring in Mannich base. Statistical significance of differences between group was determined by one-way analysis of variance (ANOVA). Among the synthesized compounds 3a, 4b, 5c, 7b, 8a and 8c were found be the most active. All the synthesized compounds were found to be low lethal as ascertained by LD50 test.
 Keywords: N- Mannich bases of heterocyclic 1,3,4-thiadiazole derivatives; Mannich reaction; antimicrobial agents; anti-inflammatory activity;