Synthesis, antimicrobial evaluation and docking studies of fluorinated imine linked 1,2,3-triazoles
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Supplementary Information
The online version contains supplementary material available at 10.1007/s11164-022-04737-2.
SUBMITTER: Kumar A
PROVIDER: S-EPMC9146814 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A new series of theophylline analogues containing 1,2,3-triazoles with different amide groups (22-41) has been designed and synthesized, and their biological activities have been evaluated as potential anticancer agents. The anticancer activities of the synthesized compounds were studied in four cancer cell lines viz. lung (A549), colon (HT-29), breast (MCF-7) and melanoma (A375). Furthermore, these compounds were screened for computational ADME and Lipinski's analysis followed by molecular docking and binding energy calculations against the various therapeutic targets involved in cell proliferation. The in vitro results demonstrate that compounds 22, 27, 36 and 40 have pivotal anticancer activity. Among these, compounds 22 and 27 have significant cytotoxic activity in all three cell lines; the in silico docking studies also reveal that compounds 22, 27 and 36 have good dock scores, binding affinities and binding energies towards human epidermal growth factor receptor 2. This is the first report to demonstrate theophylline hybrids containing 1,2,3-triazoles as potential anticancer agents.
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Project description:BackgroundNonsteroidal anti-inflammatory drugs are of vast therapeutic benefit in the treatment of different types of inflammatory conditions. 1,2,3-Triazoles and their derivatives have a wide range of applications as anti-bacterial, anti-fungal, anti-tubercular, cytostatic, anti-HIV, anti-allergic, anti-neoplastic and anti-inflammatory (AI) agents. Considering the individual biological and medicinal importance of ibuprofen and 1,2,3-triazoles, we wanted to explore novel chemical entities based on ibuprofen and triazole moieties towards their biological significance.ResultsClick chemistry has utilized as an ideal strategy to prepare novel ibuprofen-based 1,4-disubstituted 1,2,3-triazole containing molecules. These compounds were screened for their in vivo AI activity, among all the synthesized analogues 13o was shown potent effect than the reference AI drug ibuprofen at the same concentration (10 mg/kg body weight). Compounds 13l, 13g, 13c, 13k, 13i, 13n, 13m and 13j were shown significant AI activity. These triazole analogues were also screened for their bactericidal profile. Compounds 13c, 13i, 13l and 13o exhibited considerable bactericidal activity against gram positive and gram negative strains. In addition to this, molecular docking studies were also carried out into cyclooxygenase-2 active site to predict the affinity and orientation of these novel compounds (13a-q).ConclusionsIn summary, we have designed and synthesized 1,2,3-triazole analogues of ibuprofen in good yields using Click chemistry approach. AI and bactericidal activities of these compounds were evaluated and shown remarkable results.
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Project description:The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a highly effective method for the selective incorporation of deuterium atom into the C-5 position of the 1,2,3-triazole structure. Reactions of alkynes and azides can be conveniently carried out in a biphasic medium of CH(2)Cl(2)/D(2)O, using the CuSO(4)/Na ascorbate system. The mildness of the method renders it applicable to substrates of relatively high complexity, such as nucleosides. Good yields and high levels of deuterium incorporation were observed. A reaction conducted in equimolar H(2)O and D(2)O showed 2.7 times greater incorporation of hydrogen atom as compared to deuterium. This is consistent with the H(+) and D(+) ion concentrations in H(2)O and D(2)O, respectively. With appropriately deuterated precursors, partially to fully deuterated triazoles were assembled where the final deuterium atom was incorporated in the triazole-forming step.
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Project description:A highly modular approach to N-substituted 4-(1-fluorovinyl)triazoles is described. In situ desilylation and Cu-catalyzed ligation reaction of TMS-protected ?-fluoropropargyl benzothiazole sulfone with aryl, alkyl, and metallocenyl azides furnished second-generation Julia-Kocienski reagents in good to excellent yields. Condensation reactions of these reagents with aldehydes can be tuned to yield E or Z-alkenes selectively. Under mild conditions with DBU as the base, reactions of aldehydes furnished E-alkenes as the major isomer. On the other hand, in condensation reactions with LHMDS as the base and in appropriate solvents, both aldehydes and ketones reacted to yield fluoroalkenes with Z-selectivity. Stereochemical assignment of E/Z olefins obtained in the reaction of a ketone with two Julia reagents was performed via X-ray crystallographic analysis and comparisons of NMR data. The method allows efficient and ready diversification of the N1-substituent and substituents at the double bond.
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Project description:An efficient room-temperature method for the synthesis of 1-sulfonyl-1,2,3-triazoles from in situ generated copper(I) acetylides and sulfonyl azides is described. The copper(I) thiophene-2-carboxylate (CuTC) catalyst produces the title compounds under both nonbasic anhydrous and aqueous conditions in good yields.
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Project description:A tandem method for preparing 4-formyl-1,2,3-triazoles via a two-step one-pot acetal cleavage/CuAAC reaction was developed. Using this method, 4-formyl-1,2,3-triazole analogs with both electron-withdrawing and electron-donating substituents were prepared in good yield and purity. Expansion of this method to a three-step tandem reaction that incorporates an additional step of azide substitution was also successful, circumventing the need for organic azide isolation. This one-pot method, noteworthy in its simplicity and mild conditions, utilizes practical, readily available reactants and relies on protic solvent to promote acid-catalyzed acetal cleavage.
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