Kashmiri Lal

Synthesis and biological evaluation of amino acid-linked 1,2,3-bistriazole conjugates as potential antimicrobial agents

A small library of amino acid-linked 1,4-disubstituted 1,2,3-bistriazole conjugates has been synthesized from the N-protected l-amino acids propargyl esters through one-pot click reaction. All the newly synthesized compounds were tested in vitro for antimicrobial activity against Gram-positive (Staphylococcus aureus, Bacillus subtilis), Gram-negative (Escherichia coli) bacteria and fungi (Candida albicans, Aspergillus niger). The antibacterial evaluation data indicated that compounds 3c, 3h, 5a, 5b, 5c, 5d, 5e, 5g, and 5h exhibited comparable activity to standard ciprofloxacin. However, the bistriazoles 3b, 3c, 3e, 3f, and 3g showed good antifungal activity than others against both fungi. Further, docking simulation of the two most active compounds 5c against S. aureus tyrosyl tRNA synthetase and 5h into E. coli topoisomerase II DNA Gyrase B, respectively, was also performed.

One-pot synthesis and cytotoxic evaluation of amide-linked 1,4-disubstituted 1,2,3-bistriazoles

A series of amide-linked 1,4-disubstituted 1,2,3-bistriazoles have been synthesized employing copper(I)-catalyzed azide–alkyne cycloaddition reaction. All the newly synthesized compounds were screened for in vitro cytotoxicity against a panel of five human cancer cell lines; Fibrosarcoma (HT-1080), Colon (colo205, HCT-116), and Lung (A549, NCIH322). Some of the bistriazoles exhibited moderate to good activity. Compounds 3n and 3o were found to be the more active and displayed broad spectrum activity against all the cancer cell lines under investigation. Further, to study the binding modes for the two more potent compounds 3n and 3o against Human topoisomerase II, docking simulations have been carried out.

Regioselective synthesis and antimicrobial studies of ester linked 1,4-disubstituted 1,2,3-bistriazoles

A series of 1,4-disubstituted 1,2,3-bistriazoles was synthesized via click chemistry by cycloaddition of various bisalkynes with benzyl/2-phenylethyl azide. Synthesized triazoles were characterized by IR, (1)H NMR, (13)C NMR and mass spectral techniques. All the compounds were evaluated for antibacterial/antifungal activities and found to possess moderate to good antimicrobial activities. Further the docking study for the most active compound against DNA Gyrase was also carried out.

Synthesis and antimicrobial evaluation of 1,4-disubstituted 1,2,3-triazoles containing benzofused N-heteroaromatic moieties

Synthesis of a small library of 1,4-disubstituted 1,2,3-triazoles containing benzofused N-heteroaromatic moieties was carried out through click reaction of various benzofused N-heteroaromatic alkynes with aromatic azides. All the synthesized compounds were characterized by spectroscopic techniques like IR, 1H NMR, 13C NMR, mass spectrometry and evaluated in vitro for antimicrobial activity against two Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus), one Gram-negative bacteria (Escherichia coli) and two fungi (Candida albicans, Aspergillus niger). Most of the synthesized 1,4-disubstituted 1,2,3-triazoles were found to possess significant antibacterial and antifungal activity against tested microbial species. Moreover, docking simulation of the compound 1-[(1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methyl]-1H-benzo[d]imidazole was also carried out against E. coli topoisomerase II DNA gyrase B enzyme to study the binding modes and mechanism of action.Graphical abstract

Antimicrobial evaluation, QSAR and docking studies of amide-linked 1,4-disubstituted 1,2,3-bistriazoles

Abstract A series of amide-linked 1,4-disubstituted 1,2,3-bistriazoles was tested for antimicrobial activity against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, Gram-negative bacteria Escherichia coli and two fungal strains Aspergillus niger and Candida albicans. The antimicrobial evaluation data indicated that most of the compounds exhibited potential activity. To describe activity on the structural basis, QSAR studies were performed and statistically significant models were developed. Further, binding interactions of two active compounds 17 and 10 to active sites of E. coli topoisomerase II DNA gyrase B and C. albicans lanosterol 14α-demethylase (1.14.13.70) (CYPLI) (cytochrome P450 51) enzymes, respectively, were also examined.

Design, synthesis, characterization, antimicrobial evaluation and molecular modeling studies of some dehydroacetic acid-chalcone-1,2,3-triazole hybrids

A series of new dehydroacetic acid chalcone-1,2,3-triazole hybrids as potential antimicrobial agents was designed, synthesized and characterized by FTIR, NMR and HRMS spectral techniques. All the synthesized compounds were screened in vitro against four bacterial strains (Staphylococcus epidermidis, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) and two fungal strains (Aspergillus niger and Candida albicans). The antimicrobial results indicated that some of the compounds showed remarkable activities comparable to the standard drugs. Most of the compounds exhibited better efficacy compared to the DHA, which is itself an antimicrobial agent. The synergistic effect in biological activity was observed when DHA, chalcone and 1,2,3-triazole are conjugated. The molecular modeling studies of compound 5j into E. coli topoisomerase II DNA gyrase B were also performed.

Efficient synthesis and antimicrobial evaluation of 2-((1-substituted-1H-1,2,3-triazol-4-yl)-1-naphthaldehydes and their oxime derivatives

A series of 2-((1-substituted-1H-1,2,3-triazol-4-yl)-1-naphthaldehydes was prepared by the propargylation of 2-hydroxynaphthaldehyde followed by Copper(I)-catalyzed azide-alkyne cycloaddition with various organic azides. 2-((1-substituted-1H-1,2,3-triazol-4-yl)-1-naphthaldehyde analogues were transformed to corresponding oxime derivatives upon grinding with hydroxylamine hydrochloride under solvent free conditions. All the synthesized compounds were characterized by various analytical and spectral techniques and screened in vitro for antimicrobial activity. The activity data revealed that most of the compounds exhibited good to significant activities. Compounds 4c and 5c exhibited very good and broad spectrum activity towards all the tested bacterial strains. Further, to understand the binding interactions, 4c and 5c were docked into the active sites of E. coli topoisomerase II DNA gyrase.

Designed chalcone-1,2,3-triazole conjugates as potential antimicrobial agents synthesis, crystal structure and antimicrobial potential of some fluorinated chalcone-1,2,3-triazole conjugates

A simple and green synthesis of some fluorinated chalcone-triazole hybrids from propargylated chalcones and organic azides catalyzed by cellulose supported copper nanoparticles click reaction is reported. All the synthesized compounds were well characterized by various analytical and spectroscopic methods. The X-rays crystallographic study of compounds 6k revealed the self assembling properties. The antimicrobial screening results of all the synthesized compounds revealed that most of the triazole hybrids exhibited significant efficacy against tested bacterial and fungal strains. The activity results showed the synergistic effect of biological activity when two pharmacophoric units, i.e. chalcone and 1,2,3-triazole are conjugated. Further, docking simulation of the most active compounds 6p into Escherichia coli topoisomerase II DNA Gyrase B was also carried out.

Oxazolone-1,2,3-triazole hybrids: Design, synthesis and antimicrobial evaluation

BACKGROUND Oxazolones and 1,2,3-triazoles are among the extensively studied heterocycles in medicinal chemistry. Both of these moieties are reported to possess a broad spectrum of biological activity including antimicrobial. OBJECTIVE The objective of the current work is to design, synthesize and antimicrobial evaluation of some new oxazolone-1,2,3-triazole hybrids. METHODS The designed oxazolone-1,2,3-triazole hybrids were synthesized using copper(I)-catalyzed azide-alkyne cycloaddition. The antimicrobial evaluation was carried out using serial dilution method. RESULTS Most of the synthesized hybrids showed significant antimicrobial properties. Some of the compounds were found to be possessing better or comparable activity to that of the standards used. The docking simulations results are also in agreement with the antimicrobial activity data. CONCLUSION Sixteen new hybrids were synthesized and tested in vitro for their antimicrobial activity. Some of the tested compounds exhibited promising antimicrobial activity and could be utilized for the development of the lead compounds for new and more potent antimicrobial drugs.

Recent Advancements In 1, 4-Disubstituted 1H-1,2,3-Triazoles As Potential Anticancer Agents

Cancer is a class of formidable disease with high degree of mortality. Despite much progress in chemotherapy, the problem of drug resistance has led to the search for newer leads with superior efficacy. 1,2,3- Triazoles are among a vast number of nitrogen containing heterocycles studied extensively as pharmacologically important scaffolds. Recently developed copper(I)-catalyzed cycloaddition reaction between organic azides and terminal alkynes yielding 1,4-disubstituted 1,2,3-triazoles has attracted considerable attention because it allows the construction of a vast array of 1,2,3-triazoles with significant potential in pharmaceutical chemistry. In this article, an attempt to summarize the wide range of anticancer agents derived from copper(I)-catalyzed azide alkyne cycloaddition reported by the authors worldwide, has been made. This review includes articles published from 2010 onwards and summarizes the recent progress on the development of 1,4-disubstituted 1H-1,2,3-triazoles as novel anticancer chemotypes with high therapeutic indices.