The present work describes the syntheses and antimicrobial activity studies of a series of novel Schiff bases (4a–4i) and their Mannich bases (5a–5h) starting from 4-amino-3-(N-phthalimido-methyl)-1,2,4-triazole-5-thione (3). All the synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, and MS. All the synthesized compounds were screened for four Gram-negative strains, one Gram-positive strain of bacteria, and one diploid fungal strain. In general the antimicrobial activity increased remarkably on the introduction of azomethine functionality in parent triazole (3). The antimicrobial activity further improved when morpholine group was added to them except for Enterobacter cloacae, where loss of activity was observed. The results are promising and show that the fine tuning of the structures (5a, 5b, 5e, 5f, and 5h) can lead to some new antimicrobial compounds. 1. Introduction Many of the antibiotics presently in use are becoming ineffective due to the emergence of resistant microbial strains. It proves that the microbes are more intelligent than what is being anticipated by human beings, as they quickly develop mechanisms to intercept the antibiotic, thus making them ineffective. This situation demands the development of new antimicrobial agents which can deprive the microbes of their pathogenicity by novel multisite mechanisms of action [1–4]. The 1,2,4-triazole nucleus is the main structural unit of many medicines currently in market. Ribavirin (1), letrozole (2), fluconazole (3), itraconazole (4), and anastrozole (5) are a few to name which are currently in use as medicines (Figure 1). Many other 1,2,4-triazole derivatives are also known to possess pharmacological activities like antitubercular, anticonvulsant, anti-inflammatory, and analgesic activities [5–14]. It has been reported that triazoles are less susceptible to metabolic degradation and have higher target specificity and wider spectrum of activities as compared to imidazoles [15, 16]. Many heterocyclic systems having azomethine functionality are known to possess cytotoxic, antimicrobial, anticancer, and antifungal activities [17–21]. Figure 1: Some 1,2,4-triazole based medicine currently in use. The literature reveals that the presence of morpholine or piperazine ring on a heterocyclic system contributes to enhanced pharmacological activities in many cases [22–24]. This could be attributed to the increased solubility of the compounds in aqueous solvents because of the formation of aminium salt [25]. These wide applications of 1,2,4-triazole Schiff and Mannich bases motivated us to
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