Design, Synthesis, Molecular Docking Studies of Deferasirox Derivatives of 1,2,4‐Triazole as Potential Antimicrobial Agents

Abstract

A series of deferasirox derivatives of 1,2,4‐triazole (5 a–i,6 a–g) were designed and synthesized by the ring‐opening rearrangement reaction of phenyl hydrazine or its substituents and imines, compounds 5 d–i, 6 e–g are previously unknown. Obtained derivatives were characterized by IR, 1H NMR, 13C NMR, and Mass spectral. The antibacterial activities of all compounds against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans and Aspergillus niger were experimentally evaluated. Most of them exhibited potential antimicrobial activity and promising antifungal activity. Especially, 6 f and 6 g showed the best antimicrobial activity (MIC90=0.125–2.0 μg/mL) against Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli, while compounds 6 c, 6 e showed excellent antifungal activity (MIC90=0.5–2.0 μg/mL). The molecular docking analysis further revealed that all the synthesized derivatives have shown potential binding affinities.

Synthesis of Benzimidazole-1,2,4-triazole Derivatives as Potential Antifungal Agents Targeting 14α-Demethylase

“…Carbendazole, benomyl, and thiabendazole have been frequently used among them. − Triazoles, a type of heterocyclic molecule, are favored scaffolds in a variety of fields. Fluconazole, itraconazole, and voriconazole are antifungal medicines available for therapeutic use that contain 1,2,4-triazole fragments. − In recent years, many studies have been conducted on the antifungal activities of triazoles. − Antifungal drugs with benzimidazole and triazole structures and the chemical structure of the designed compounds are shown in Figure .…”

“…Fluconazole, itraconazole, and voriconazole are antifungal medicines available for therapeutic use that contain 1,2,4-triazole fragments. 21 − 24 In recent years, many studies have been conducted on the antifungal activities of triazoles. 25 − 28 Antifungal drugs with benzimidazole and triazole structures and the chemical structure of the designed compounds are shown in Figure 2 .…”

Recent Advances in Pharmacologically Important 1,2,4-Triazoles as Promising Antifungal Agents against Candida Albicans

“…However, it is important to note that despite its efficacy, compound 34f remains less potent than fluconazole, which possesses a MIC of 0.78 µg/ml. Several compounds (34c, 34d, 32b, 33b, 36a, 35c, 35e, 35g, 35h, and 35i) derived from the series of benzyl and alkyl ethers substituted with furyl groups exhibited considerable antifungal activity against C. Yiping Hu and colleagues have successfully developed and synthesized 1,2,4-triazole Deferasirox analogues [14] .These derivatives, denoted as 39a-i and 40a-g, were obtained using a method of ring opening using phenyl hydrazine or its substitutes in combination with imines. However, compounds 40c and 40e exhibited notable antifungal efficacy against Candida albicans, with a (MIC) value ranging from 0.5 to 2.0 μg/mL.…”

“…Azoles are a class of heterocyclic compounds that serve as privileged scaffolds in various domains [10,11]. Their derivatives have shown promise as antifungal agents, primarily by impeding the synthesis of ergosterol, a key constituent of the fungal cell membrane [12,13].This inhibition is achieved through the suppression of the fungal cytochrome P450 enzyme, ultimately resulting in fungal apoptosis [14]. Moreover, azole based compounds possess various biological activity such as, anticonvulsants, antidepressants, antioxidants, antiinflammatory agents, antibiotics, anti-fungal agents, antiviral agents, and so on [15].…”