Design, synthesis, antimicrobial evaluation and in silico studies of symmetrical bis (urea-1,2,3-triazole) hybrids
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Design, synthesis, antimicrobial evaluation and in silico studies of symmetrical bis (urea‑1,2,3‑triazole) hybrids Nisha Poonia1 · Kashmiri Lal1 · Ashwani Kumar2 Received: 11 September 2020 / Accepted: 23 October 2020 © Springer Nature B.V. 2020
Abstract In search of 1,2,3-triazole-based antimicrobials, some symmetrical bis(urea-1,2,3triazole) hybrids were synthesized via clicked Huisgen cycloaddition. The structural characterization was done by different physical and spectral techniques like NMR, FTIR and HRMS. In vitro antimicrobial evaluation of all the synthesized compounds was performed against three bacterial strains (Staphylococcus epidermidis, Escherichia coli and Bacillus subtilis) and two fungal strains (Aspergillus niger and Candida albicans). All the synthesized urea-linked bis(1,2,3-triazole) hybrids (4a–4o) were found to exhibit higher potency than their alkyne precursors (3a–3c). Also, all the synthesized hybrids elicited better antifungal activity than the reference drug Fluconazole against both the fungal strains. Compound 4e and 4o were found to be more potent toward C. albicans with lowest MIC values 0.0112 µmol/ mL and 0.0105 µmol/mL, respectively. The docking studies of compounds 4e and 4o and their respective alkynes 3b and 3c were carried out in the active site of sterol 14-α-demethylase of C. albicans. Graphic abstract
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116 4-020-04318-1) contains supplementary material, which is available to authorized users. Extended author information available on the last page of the article
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Keywords Urea · Bis-triazoles · Antimicrobial activity · In silico studies
Introduction The day-by-day increase in antimicrobial resistance has hampered the effective treatment of different human diseases caused by various microbes. There is a need for integral efforts to develop methodologies to provide new classes of drugs with better efficacy and low toxicity because the cases of multidrug resistance among various microorganisms toward currently available drugs continue to spread inevitably [1–4]. In this regard, clicked Huisgen cycloaddition chemistry has evolved as an important strategy for rapid and selective synthesis of 1,4-disubstituted 1,2,3-triazoles [5–7]. This cycloaddition has been proved to be a very useful technique in the functional modification of biomolecules mainly because of its high selectivity, yield and biocompatibility as well as its stability toward metabolic degradation [8–11]. This reaction has been studied extensively because of its number of applications counting drug discovery [12, 13], bioconjugation [14], ion recognition [15], polymer chemistry [16], radiochemistry, etc. 1,4-Disubstituted 1,2,3-triazoles possess high dipole moment, and exhibit various interactions like Van der Waals forces, hydrogen bonding, dipole–dipole, hydrophobic and other non-covalent interactions with a diversified range of biomolecular targets [17]. Organic molecu
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