Synthesis, antifungal and antibacterial activity of novel 1,2,4-triazole derivatives

Abstract

A large number of 1,2,4-triazole-containing ring system have been incorporated into a wide variety of therapeutically interesting drug candidates including anti-inflammatory, central nervous system stimulants, antianxiety, and antimicrobial agents. To overcome the rapid development of drug resistance, new agents should preferably have chemical characteristics that clearly differ from those of existing agents. Thus led to the design and synthesize the new antimicrobial agents. A novel series of Schiff bases based on of 4-(benzylideneamino)-5-phenyl-4H-1,2,4-triazole-3-thiol scaffold was prepared by heating thiocarbohydrazide and substituted benzoic acid and subsequently, treating with substituted benzaldehydes. Seventeen derivatives were synthesized and were biologically screened for antifungal and antibacterial activity. The newly synthesized derivatives of triazole showed antifungal activity against fungal species, Microsporum gypseum; and antibacterial activity against bacterial species, Staphylococcus aureus. It was observed that none of the compounds tested showed positive results for fungi Candida albicans fungi Aspergillus niger, nor against bacterial strain Escherichia coli. Strong antifungal effects were obtained for the synthesized compounds against M. gypseum and were superior or comparable to standard drug ketoconazole. Similarly, all of the synthesized compounds exhibit strong antibacterial activity against S. aureus and were superior or comparable to standard drug streptomycin. It was found that among the triazole derivatives so synthesized, six of them, showed antifungal activity superior to ketoconazole while one of them, showed antibacterial activity superior to streptomycin. Thus, these can be the potential new molecule as an antimicrobial agent.

Design, synthesis and pharmaco-toxicological assessment of 5-mercapto-1,2,4-triazole derivatives with antibacterial and antiproliferative activity

“…The triazole derivatives revealed a similar moderate antifungal and antibacterial activity with no visible variations between structures. Gupta and Jain (17) synthesized a set of Shiff bases, also based on the 5-mercapto-1,2,4-triazole scaffold, showing good antimicrobial activity; the moderate antimicrobial activity of our three synthesized compounds can be explained by comparison, taking into account the main structural similarities between the two sets of compounds: i) The main scaffold represented by the 5-mercapto-1,2,4-triazole moiety; ii) the substituted phenyl radical in the fifth position; and iii) a non-substituted thiol group in the third position. Nevertheless there are two main structural differences that consist in the absence of a radical in the fourth position (substituted bezylideneamino radical) and of halogen substitution of the phenyl radical from the fifth position (17), differences that may justify the weaker antibacterial activity of our triazole compounds.…”

“…A series of 25 compounds bearing the 1,2,4-triazole moiety have been synthesized and assessed as antitumor agents through docking simulation in target protein structures (RCSB PDB ID: 1YS1, 1FM6, 1BXL) and in in vitro antitumor screening, revealing significant activity on leukemia, melanoma, lung and ovarian cancer cell lines (15). In addition, a significant number of synthesized 1,2,4-triazole derivatives has been reported with significant antibacterial activity (16,17). …”

4‐Chlorothiazole‐5‐carbaldehydes as Potent Precursors for Synthesis of Some New Pendant N‐heterocyces Endowed with Anti‐Tumor Activity

“…Similarly, compound 5 reacted with equimolar amount 3-amino-1,2,4-triazole, 6-amino-2thioxo-2,3-dihydropyrimidin-4(1H)-one, 6-amino-2thioxo-2,3-dihydropyrimidin-4(1H)-one, 2-cyanomethyl benzimidazole, and 2-amino benzimidazole to yield the corresponding fused thiazolo[4,5-d]pyrimidine analogues 26-30 (Scheme 4). The structures of these compounds (25)(26)(27)(28)(29)(30) were established on the base of their correct elemental analysis and spectral data. For instance, the IR spectra of these compounds showed the lack of formyl absorption band around 1720 cm À1 , beside the presence of characteristic singlet signal attributed to the pyrimidine-C4 proton around 8.78 ppm in their 1 H NMR spectra.…”

“…Yellow powder from MeOH in 80% yield; mp 228-230°C; IR (KBr): (cm À1 ) 1610-1620 (4 C═N str ), 1720 (C═O str ); 1 1H-1,2,4-triazol-1-yl)-5-thioxo-4,5-dihydrothiazolo[4,5-b] pyridine-6-carbonitrile (24). Yellow crystals from EtOH in 85% yield; mp 248-250°C; IR (KBr): (cm À1 ) 1329 (C═S str ), 1612-1625 (4 C═N str ), 2225 (C≡N str ), 3354 (N─H str ); 1 General procedure for the reaction of compound 5 with N, N-binucleophiles to synthesize the compounds (25)(26)(27)(28)(29)(30). To a solution of compound 5 (0.44 g, 1 mmol) in EtOH (30 mL) containing Et 3 N (0.5 mL), an equimolar amount of appropriate heterocyclic amines, namely, 5-amino-3-phenyl-1H-pyrazole, 3-amino-1,2,4-triazole, 6-amino-2-thioxo-2,3-dihydropyrimidin-4(1H)-one, 6amino-2-thioxo-2,3-dihydro pyrimidin-4(1H)-one, 2cyanomethyl benzimidazole, and 2-amino benzimidazole was added then reaction mixture was refluxed for 10-12 h. The reaction progress was checked by TLC.…”

Pyrazole‐1‐carbothioamide as a Potent Precursor for Synthesis of Some New N‐heterocycles of Potential Biological Activity

“…Recently, 1,2,4-triazole annulated compounds were reported as potential anticonvulsant [33][34][35] and anti-HIV agents [36,37]. In addition, a vast number of synthesized 1,2,4-triazole analogs have been reported with significant antibacterial, antifungal, antiviral, antituberculosis, anti-inflammatory, anticonvulsant, antidepressant, and anticancer activities [38][39][40].…”