Synthesis, Biological Evaluation, Molecular Docking, and Acid Dissociation Constant of New Bis‐1,2,3‐triazole Compounds

Abstract

In this study, new bis-1,2,3-triazole derivatives, N,N'-(1,3phenylene)bis(2-(4-R-1H-1,2,3-triazol-1-yl)acetamide), were synthesized by copper-catalyzed azide-alkyne cycloaddition click chemistry in 84-96 % yield. A wide range bioactivity screening was performed to determine DNA cleavage, antioxidant, antibacterial and antifungal activities. All of the synthesized bis-1,2,3-triazoles showed excellent DNA cleavage activity and 4 e, bearing 2-bromoethyl moiety as a substituent, was almost degraded all of the plasmid DNA. Molecular docking simulations suggest that the synthesized compounds act as minor groove binders of DNA. The antioxidant activities of the bis-1,2,3-triazoles were determined based on the radical scavenging effect of the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and iron chelating activity. The compounds exhibited effective iron chelating activity at 200 mg/L while showing a moderate ability to scavenge DPPH radical. The compounds exhibited antibacterial activity against B. cereus, L. pneumophila subsp. pneumophila, S. aureus, P. aeruginosa, E. coli and E. hirae bacterial strains, and antifungal activity against C. albicans and C. tropicalis microfungus strains with a MIC value in the range of 4-128 μg/mL. 4 d, bearing cyclohexylmethyl moiety as substituent, exhibited a broadspectrum antimicrobial activity (both antibacterial and antifungal). Four different acid dissociation constant (pK a ) values of each product were determined potentiometrically in 20 % (v/v) dimethyl sulfoxide-water at 25 � 0.1°C, at an ionic background of 0.1mol/L of NaCl using the HYPERQUAD program.

1,2,3‐Triazole Derivatives as an Emerging Scaffold for Antifungal Drug Development against Candida albicans: A Comprehensive Review

“…Structure‐activity studies suggested that substituted phenyl ring with methoxy group at the triazole nucleus was suitable for the antifungal activity. The substitution of nitro and methyl group at the ortho and meta position was equipotent but was less than the methoxy group substitution [47] . Similarly, Deshmukh et al .…”

“…The substitution of nitro and methyl group at the ortho and meta position was equipotent but was less than the methoxy group substitution. [47] Similarly, Deshmukh et al synthesised piperazine and amide linked dimeric 1,2,3-triazoles and screened them for their activity against Candida albicans. The results indicated that compound 19 was most active antifungal candidate against Candida albicans with MIC value of 30.84 μmol/mL.…”

Click chemistry: A fascinating, Nobel-winning method for the improvement of biological activity

“…As is well known, until today, among the most known triazole compounds in terms of their activities and uses, Ticagrelor, Rufinamide, Cefatrizine, Tazobactam, Carboxyamidotriazole (CAI), tert-Butyldimethylsilylspiroaminooxathioledioxide (TSAO), Volitinib, Redezolid and Solithromycin have taken part as approved drugs or clinical trials/drug candidates [67][68][69][70] . In order to synthesize the examples given and other many 1,2,3-triazole compounds in the literature, copper catalyzed azide-alkine cycloaddition (CuAAC) reactions under Huisgen's temperature catalyzed azide-alkyne 1,3-dipolar [3+2] cycloaddition and so click chemistry classification have been continuing their popularity from past to present.…”

Trifluoromethylated Amidrazone Derivatives as Key Compounds for the Synthesis of 4-Aryl-3,5-bis(trifluoromethyl)-4H-1,2,4-triazoles

“…Triazole scaffolds are very interesting in medicinal chemistry and to organic chemists in recent years due to their unique biological activities, 1 such as antimicrobial, 2 antioxidant, 3 anticancer, 4 antiviral, 5 anti-inflammatory, 6 antitubercular, 7 antihypertensive, 8 antiurease, 9 anticonvulsants, 10 antidiabetic, 11 and antidepressant. 12 Among these compounds, 1,2,4-triazoles are considered to be more remarkable isomers in pharmacology, because of their synthetic utility and wide spectrum of biological activities.…”