Regioselective Synthesis, Antibacterial, Molecular Docking and Fingerprint Applications of 1‐Benzhydrylpiperazine Derivatized 1,4‐Disubstituted 1,2,3‐Triazoles

Abstract

A series of ten 1,4‐Disubstituted 1,2,3‐Triazoles having 1‐benzhydrylpiperazine chemical scaffold were synthesized by one pot Cu (I) catalyzed click reaction and evaluated for their antibacterial activity against Escherichia Coli and Staphylococcus aureus by agar well diffusion method. Amongst all, 2‐chloro‐6‐fluorobenzyl substituted 1,2,3‐Triazole 7 e and 2,4‐dichlorobenzyl Triazole 7 f found to be more active compared to the Ciprofloxacin. To rationalize the binding interaction of compounds and the protein at active site, we performed Molecular docking study using a bacterial DNA Gyrase B protein. The docking energy of 2‐chloro‐6‐fluorobenzyl substituted Triazole 7 e and 2,4‐dichlorobenzyl Triazole 7 f was observed as −22.498 and −22.569 kcalmol−1 in comparison to reference drug Ciprofloxacin whose docking energy is −22.072 kcal mol−1. It also makes several hydrogen bonds with our conserved residue Ser55, Asp81 and Ile86. Furthermore, several hydrophobic contacts were also observed within the pocket. Finally, Latent fingerprint detection study indicated that the compound unsubstituted Triazole 7 a powder shows good adhesion and finger ridge details without back ground staining. The demonstrated method can be applied to detect fingerprints on all types of smooth surfaces and hence, it can be easily adopted for latent fingerprint detection. The in vitro and in silico activities conclusively revealed that our lead compounds may be used as a novel antibacterial agents.

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

“…A set of 1,4-disubstituted 1,2,3-triazoles tethered to a benzhydrylpiperazine fragment were assayed for their antibacterial potentials against S. aureus and E. coli using the agar well diffusion method. 98 The triazole derivatives 63 and 64 (Fig. 7) were found to be more active than ciprofloxacin was (zones of inhibition: 16.33 and 16.45 mm against S. aureus; 15.63 and 16.15 mm against E.coli respectively).…”

Fluorinated triazoles as privileged potential candidates in drug development—focusing on their biological and pharmaceutical properties

“…Govindaiah and coworkers have synthesized a fluorinated 1,2,3-triazole derivatives bearing benzhydrylpiperazine moiety 121 ( Supplementary Table S1 ) ( Govindaiah et al, 2018 ). Using agar well diffusion method on E. Coli and S. aureus , antibacterial screening was carried out for compound 121 .…”

Novel 1,2,3-triazole-1,4-dihydropyridine-3,5-dicarbonitrile derivatives: synthesis and antibacterial evaluation

“…By docking study, it was also found that these two compounds make several hydrogen bonds with DNA Gyrase B of bacteria. 28 Functionalized 1,2,3-triazole nucleosides, 4-chlorophenyl derivative 3a, and 3-methylthiophen derivative 3b displayed significant antibacterial activity against many Gram-positive and Gram-negative organisms. The 4-chlorophenyl derivative of functionalized 1,2,3-triazole nucleosides inhibited E. coli ATCC 10536 with a zone of inhibition of 30 mm that was nearer to zone obtained by standard Cefotaxime (34 mm).…”