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A series of novel N1-triazolo-4-(2-hydroxyphenyl)-1,5-benzodiazepin-2-ones 7a-e and N5-triazolo-4-(2-acetoxyphenyl)-1,5-benzodiazepin-2-ones 8a-e were designed and synthesized in good yields via a Cu(I) catalyzed 1,3-dipolar alkyne-azide coupling reaction (CuAAC) between the N1- and N5-propargyl-1,5-benzodiazepines 2 and 5 respectively and various arylazides 6a-e. Photophysical properties were investigated for all the obtained triazolo-benzodiazepine hybrids by mean of absorption and fluorescence spectral techniques. Thus, a fluorescent emission was detected for the derivatives 7a-e in aggregated state. On another hand, the O-acetylated derivatives 8a-e were found to be not emissive. Finally, we have chosen a model reaction to demonstrate that upon deprotecting the -OAc group in the N1, N5-disubstituted benzodiazepine 8d a moderate fluorescence reappeared in the obtained product 9d proving that an ESIPT process can take place as long as the hydroxyl group remains free, allowing the OH/C[dbnd]O proton transfer to occur. A computational study of compounds 7e and 9d in vacuo provide further details and arguments to rationalize the fluorescence of these compounds in aqueous mixtures.

Nitro compounds are known to change reaction rates and kinetic concentration dependence of Br?nsted-acid-catalyzed reactions. Yet, no mechanistic model exists to account for these observations. In this work, an atomistic model for the catalytically active

Baicalin and its aglycone baicalein derived from Scutellaria baicalensis exhibited potent anticancer effects in various types of cancer cell lines. However, the unfavorable pharmaceutical properties became the main obstacle for their potential clinical de

A simple and efficient protocol has been developed for the synthesis of new1,2,3-triazole-2,3-dihydroquinazolin-4[1H]-one (DHQ) conjugates(6a?j) via ultrasound-assisted, solvent-free ionic liquid [HDBU][HSO4]-catalyzed reaction in good to excellent yields. This non-conventional, ultrasound-assisted route has taken the reactions over the conventional reflux method to provide good to excellent yields of the corresponding products (6a?j) in a very short time. In addition, mild reaction conditions, tolerance to functionalized substrates, ease of product isolation, prevention of its over oxidation and reusability of catalyst [HDBU][HSO4] are some key striking features of the methodology. The newly synthesized derivatives (6a?j) were screened for antioxidant activity using 1,1-diphenyl-2-picryl hydrazyl (DPPH) assay and are found to be a potent scavenger. The compounds 6b, 6c, 6d, 6e and 6i showed significant antioxidant activity. Molecular docking studies showed significant binding affinity in the active site of myeloperoxidase (MPO) enzyme and hence scavenged by inhibition of MPO. In silico ADMET and pharmacokinetic studies of the conjugates are very promising; a cumulative body of evidence suggests their medicinal value as a potential orally active drug candidate. Graphical abstract: [Figure not available: see fulltext.]

Since the starch biopolymer is an available and inexpensive matrix with modifiable functionality and stabilization capability for metal ions, in this report, we oxidized it to dialdehyde form for the further functionalization with vitamin B1 as a green σ-donor and π-acceptor carbene type ligand. Immobilization of vitamin B1 on this biopolymer was done through imine bond formation between NH2 groups of aminopyrimidine segment of vitamin B1 and aldehyde functional groups of starch oxide. Thiazolium heterocycle part in this biomolecule provided a carbene type precursor for the metal complexation. After the magnetization process by using of Fe3O4 nanoparticles that lead to quick and facile magnetic separation and metal catalyst recycling, copper ions immobilized on the magnetic support (5.9 wt% Cu, 0.93 mmol/g). The prepared copper N-heterocyclic carbene complex (Fe3O4@DAS@VB1@CuCl nanocomposite) was characterized by FT-IR, SEM, EDX, XRD, VSM, TGA and ICP-OES analysis and then its catalytic activity investigated in azidonation of arylboronic acids and also one-pot coupling reaction of the synthesized aryl azides with phenylacetylene. 1,4-Diaryl 1,2,3-triazoles were obtained in excellent yields (≥90%) at proper reaction times (30–200 min). The magnetic catalyst was recovered by a magnetic field and reused in azidation reaction up to 7 cycle.

Starting from our previously reported hit, a series of 1,5-diaryl-1,2,3-triazole-4-carbohydrazones were synthesized and evaluated as inhibitors of the YAP/TAZ-TEAD complex. Their binding to hTEAD2 was confirmed by nanodifferential scanning fluorimetry, an

Carbon isotope labeling is a traceless technology, which allows tracking the fate of organic compounds either in the environment or in living organisms. This article reports on a general approach to label urea derivatives with all carbon isotopes, including14C and11C, based on a Staudinger aza-Wittig sequence. It provides access to all aliphatic/aromatic urea combinations.

Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC50 values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that compound 29b concentration-dependently induced H3K4me1/2 accumulation in LSD1 overexpressed MGC-803 cells and also inhibited metastasis of MGC-803 cells. Collectively, both compounds could be promising lead compounds for further investigation.

CDK4 & CDK6 are essential regulators of initial cell cycle phases and are always considered an exciting choice for anti-cancer therapy. In the present study, we presented the structure-based rational design & synthesis of a new class of 1,2,3-triazole tet

Abstract: Antimicrobial resistance has become a significant threat to global public health, thus precipitating an exigent need for new drugs with improved therapeutic efficacy. In this regard, molecular hybridization is deemed as a viable strategy to afford multi-target-based drug candidates. Herein, we report a library of quinoline—1H-1,2,3-triazole molecular hybrids synthesized via copper(I)-catalyzed azide-alkyne [3 + 2] dipolar cycloaddition reaction (CuAAC). Antimicrobial evaluation identified compound 16 as the most active hybrid in the library with a broad-spectrum antibacterial activity at an MIC80 value of 75.39?μM against methicillin-resistant S. aureus, E. coli, A. baumannii, and multidrug-resistant K. pneumoniae. The compound also showed interesting antifungal profile against C. albicans and C. neoformans at an MIC80 value of 37.69 and 2.36?μM, respectively, superior to fluconazole. In vitro toxicity profiling revealed non-hemolytic activity against human red blood cells (hRBC) but partial cytotoxicity to human embryonic kidney cells (HEK293). Additionally, in silico studies predicted excellent drug-like properties and the importance of triazole ring in stabilizing the complexation with target proteins. Overall, these results present compound 16 as a promising scaffold on which other molecules can be modeled to deliver new antimicrobial agents with improved potency. Graphic abstract: [Figure not available: see fulltext.].

According to the World Health Organization, snakebite envenoming is a neglected disease that affects around 5.4 million people worldwide each year. In Brazil, in 2019 there were 29,000 cases of accidents, with 104 deaths. The genus Bothrops was responsibl

The molecular chaperone heat shock protein 90 (Hsp90) is a promising target for cancer therapy. Natural product aconitine is a potential Hsp90 inhibitor reported in our previous work. In this study, we designed and synthesized a series of 2-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-2-azabicyclo[3.2.1]octan-3-one derivatives as potent Hsp90 inhibitors by simplifying and modifying aconitine scaffold. Among these compounds, 14t exhibited an excellent antiproliferative activity against LoVo cells with an IC50 value of 0.02 μM and a significant Hsp90α inhibitory activity with an IC50 value of 0.71 nM. Molecular docking studies provided a rational binding model of 14t in complex with Hsp90α. The following cell cycle and apoptosis assays revealed that compound 14t could arrest cell cycle at G1/S phase and induce cell apoptosis via up-regulation of bax and cleaved-caspase 3 protein expressions while inhibiting the expressions of bcl-2. Moreover, 14t could inhibit cell migration in LoVo and SW620 cell lines. Consistent with in vitro results, 14t significantly repressed tumor growth in the SW620 xenograft mouse model.

At present therapeutic options for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are very limited. We designed and synthesized three sets of small molecules using quinoline scaffolds. A series of quinoline conjugates (10a-l, 11a-c, and 12a-

A library of 1,2,3-triazole-incorporated thymol-1,3,4-oxadiazole derivatives (6–18) hasbeen synthesized and tested for anticancer and antimicrobial activities. Compounds 7, 8, 9, 10, and 11 exhibited significant antiproliferative activity. Among these act

Chemotherapy is the most common clinical treatment for non-small cell lung cancer (NSCLC), but low efficiency and high toxicity of current chemotherapy drugs limit their clinical application. Therefore, it is urgent to develop hypotoxic and efficient chemotherapy drugs. Theophylline, a natural compound, is safe and easy to get, and it can be used as a modified scaffold structure and hold huge potential for developing safe and efficient antitumor drugs. Herein, we linked theophylline with different azide compounds to synthesize a new type of 1,2,3-triazole ring-containing theophylline derivatives. We found that some theophylline1,2,3-triazole compounds showed a good tumor-suppressive efficacy. Especially, derivative d17 showed strong antiproliferative activity against a variety of cancer cells in vitro, including H460, A549, A2780, LOVO, MB-231, MCF-7, OVCAR3, SW480, and PC-9. It is worth noting that the two NSCLC cell lines H460 H and A549 are sensitive to compound d17 particularly, with IC50 of 5.929 ± 0.97?μM and 6.76 ± 0.25?μM, respectively. Compound d17 can significantly induce cell apoptosis by increasing the ratio of apoptotic protein Bax/Bcl-2 by downregulating the expression of phosphorylated Akt protein, and it has little toxicity to normal hepatocyte cells LO2 at therapeutic concentrations. These data indicate that these theophylline acetic acid-1,2,3-triazole derivatives may be potential drug candidates for anti-NSCLC and are worthy of further study.

Abstract: A series of triazolyl-modified podophyllotoxin analogs have been designed and synthesized by utilizing Huisgen 1,3-dipolar cycloaddition in order to develop potent antitumor agents. The synthesized analogs were assessed for in vitro anticancer a

Abstract: Curcumin is an active component of turmeric that has poor solubility, stability and bioavailability. The monocarbonyl curcumin analogues were modified from curcumin to achieve more stable and active compounds as compared to curcumin. Therefore,

Isoxazole-triazole conjugates (8a-q) were synthesized using click chemistry approach and their biological activities were explored to develop novel antibacterial agents. In vitro antibacterial screening against Gram-positive as well as Gram-negative bacterial strains identified compounds 8b and 8m with potent inhibitory potential against selective bacterial cells. 8b showed IC50 value of 67.6 μg/mL against P. aeruginosa while 8m exhibited better activity against Gram-positive bacteria S. pneumoniae and E. faecalis having IC50 values 74.13 and 44.7 μg/mL, respectively. Effect on growth kinetics of the bacterial cells as well as cytotoxicity studies on human embryonic kidney cells (HEK293) further supports their biological potential. Compound 8m significantly inhibited biofilm formation of E. coli cells visualized by scanning electron microscopy (SEM) analysis. The interaction of these compounds with ctDNA, as their possible mode of action, was studied using multi-spectroscopic techniques and molecular docking. The data suggested that compound 8m intercalate in the minor groove of DNA.

A series of homoerythrina alkaloid derivatives containing a 1,2,3-triazole moiety as PARP-1 inhibitors were designed and synthesized. And their anti-proliferative activity was further evaluated. Compound 10n had excellent activity to inhibit proliferation of A549 cells (IC50 = 1.89 μM), which was higher than harringtonine (IC50 = 10.55 μM), pemetrexed (IC50 = 3.39 μM), and rucaparib (IC50 = 4.91 μM). Furthermore, the selectivity index of compound 10n was higher than rucaparib and pemetrexed for lung cancer cells. Flow cytometry analysis showed that compound 10n significantly arrested the cell cycle in the S phase, then induced apoptosis of A549 cells (apoptosis rate is 46%), which effectively inhibited cell proliferation. Simultaneously, western blot analysis revealed that compound 10n could prevent the biosynthesis of PAR. Further analysis results revealed that compound 10n could inhibit the expression of cyclin A, down-regulate the expression of bcl-2/bax, activate caspase-3, and ultimately induce apoptosis of A549 cells. All the results indicated that compound 10n had potential research value as a novel PARP-1 inhibitor in antitumor, and it provided a new reference for further development of PARP-1 inhibitors.

Inhibitors of poly (ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer, and many researchers are interested in the development of new PARP-1 inhibitors. Herein, we designed and synthesized 44 novel erythrina derivatives bearing a 1,2,3-triazole moiety as PARP-1 inhibitors. MTT assay results indicated that compound 10b had the most potent anti-proliferative activity against A549 cells among five cancer cells. The enzyme inhibitory activity in vitro of compound 10b was also significantly better than rucaparib. Furthermore, the selectivity index of compound 10b was higher than rucaparib for lung cancer cells. Flow cytometry analysis showed that compound 10b induced apoptosis of A549 cells by the mitochondrial pathway. Western blot analysis indicated that compound 10b was able to inhibit the biosynthesis of PAR effectively, and it was more potent than rucaparib. Also, compound 10b was able to up-regulate the ratio of bax/bcl-2, activate caspase-3, and ultimately induced apoptosis of A549 cells. The combined results revealed that the discovery of novel non-amide based PARP-1 inhibitors have great research significance and provide a better choice for the future development of drugs.

Novel triazole-porphyrin derivatives (TZ-PORs) were synthesized through the Heck reaction and then incorporated into polyvinylpyrrolidone (PVP) micelles. After verifying that this incorporation did not compromise the photophysical and chemical features of

Carbonic anhydrase IX (CAIX) is an emerging drug target for hypoxia associated cancers. To identify potent and selective inhibitors of CAIX, a small library of ferulic acid (FA) derivatives bearing triazole moiety has been designed, synthesized and evaluated against different human CA isoforms (CAII, CAVA & CAIX). Though most of the compounds showed CAIX inhibition in the micromolar range, compound 7i selectively inhibits CAIX in the nanomolar range (IC50 = 24 nM). In silico analysis revealed binding of 7i with the catalytically important amino acid residues of CAIX. Further, cell-based studies indicate that 7i inhibits the activity of CAIX, decreases the epithelial to mesenchymal transitions, induces apoptosis, inhibits cell migration and colonization potential of cancer cells. Taken together, these results emphasized the use of 7i as a prospective pharmacological lead molecule in CAIX targeted anticancer therapeutics.

Gankyrin is an oncoprotein overexpressed in numerous cancer types and appears to play a key role in regulating cell proliferation, cell growth, and cell migration. These roles are largely due to gankyrin's protein-protein interaction with the 26S proteaso

In an effort to develop a potent anti-malarial agent against Plasmodium falciparum, a structure-guided virtual screening using an in-house library comprising 652 compounds was performed. By docking studies, we identified two compounds (JMI-105 and JMI-346

The photodecomposition of azides to generate nitrenes usually requires wavelengths in the 300 nm region. In this study, we show that this reaction can be readily performed in the UVA region (368 nm) when catalyzed by Pd-decorated TiO2. In aqueous medium the reaction leads to amines, with water acting as the H source; however, in non-protic and non-nucleophilic media, such as acetonitrile, nitrenes recombine to yield azo compounds, while azirine-mediated trapping occurs in the presence of nucleophiles. The heterogeneous process facilitates catalyst separation while showing great chemoselectivity and high yields.

Oleanolic acid (OA) and its semi-synthetic derivatives have been reported to have a wide range of biological activities. The introduction of electrophilic Michael acceptor group can increase the reactivity of OA to cellular targets and thus improve the an

The copper(I)-exchanged zeolite CuI-USY proved to efficiently catalyze the direct azidation of arylboronic acids with sodium azide under simple and practical conditions, namely at room temperature under air with methanol as solvent and without any additive. This easy-to-prepare and cheap catalytic material has been demonstrated to be recyclable and the mild azidation conditions further showed good functional-group tolerance, leading to a variety of substituted (hetero)aryl azides (18 examples). Interestingly, the azidation reaction has been successfully coupled to a CuAAC reaction, thus allowing access to triazoles from arylboronic acids via a one-pot CuI-catalyzed process.

A mixed CuI/CuIIcatalyst based on magnetic cysteine functionalized graphene oxide (CuI/II@Cys-MGO) was prepared and used for the azidonation reaction of aryl boronic acids and one-pot synthesis of 1,4-diaryl ?1,2,3-triazoles. Aryl azides were obtained in good yields and short reaction times via cross-coupling of aryl boronic acids with sodium azide in the presence of CuII catalytic species in this catalytic system. The azide-alkyne cycloaddition reaction was catalyzed by CuI catalytic species in CuI/II@Cys-MGO nanocomposite.

A new hybrid polydentate template comprising distinctive pharmacophoric groups, namely, ibuprofen, 1,3,4-oxadiazole, and 1,2,3-triazole linked through a thioether bridge was achieved by one-pot synthesis by exploring multicomponent Cu-catalyzed “click chemistry” approach. The target structures were characterized by NMR, IR, and LC-Mass. The X-ray analysis of 2-(1-(4-isobutylphenyl)ethyl)-5-(((1-(3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-1,3,4-oxadiazole (8a) confirmed the assigned structure. The in vitro antibacterial and anticancer activity of these compounds revealed that 2-(1-(4-isobutylphenyl)ethyl)-5-(((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)thio)-1,3,4-oxadiazole (8b) demonstrated more potent antibacterial activity against Gram-negative strains (Escherichia coli and Pseudomonas aeruginosa) and 2-(((1-(2,4-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5-(1-(4 isobutylphenyl)ethyl)-1,3,4-oxadiazole (8e) exhibited anticancer activity with IC50 of 27.50 and 31.03?μg/mL against HeLa and MCF-7 cell lines, respectively.

Wnt/β-catenin signaling pathway is implicated in the etiology and progression of metabolic disorders. Although lines of genetic evidence suggest that blockage of this pathway yields favorable outcomes in treating such ailments, few inhibitors have been used to validate the promising genetic findings. Here, we synthesized and characterized a novel class of triazole-based Wnt/β-catenin signaling inhibitors and assessed their effects on energy metabolism. One of the top inhibitors, compound 3a, promoted Axin stabilization, which led to the proteasome degradation of β-catenin and subsequent inhibition of the Wnt/β-catenin signaling in cells. Treatment of hepatocytes and high fat diet-fed mice with compound 3a resulted in significantly decreased hepatic lipid accumulation. Moreover, compound 3a improved glucose tolerance of high fat diet-fed mice without noticeable toxicity, while downregulating the genes involved in the glucose and fatty acid anabolisms. The new inhibitors are expected to be further developed for the treatment of metabolic disorders.

Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety. Among them, compound 31f was identified as the best APN inhibitor with IC50 value being two orders of magnitude lower than that of the positive control bestatin. Compound 31f possessed selective cytotoxicity to several tumor cell lines over the normal cell line human umbilical vein endothelial cells (HUVECs). Notably, when combined with 5-fluorouracil (5-Fu), 31f exhibited synergistic anti-proliferation effect against several tumor cell lines. At the same concentration, 31f exhibited much better anti-angiogenesis activities than bestatin in the HUVECs capillary tube formation assay and the rat thoracic aorta rings test. In the in vitro anti-invasion assay, 31f also exhibited superior potency over bestatin. Moreover, considerable in vivo antitumor potencies of 31f alone or in combination with 5-Fu were observed without significant toxic signs in a mouse heptoma H22 tumor transplant model.

A series of asiatic acid (AA) based 1,2,3-triazole derivatives were designed, synthesized and subjected to a cell-based NF-κB inhibition screening assay. Among the tested compounds, compound 6k displayed impressive NF-κB inhibitory activity with an ICsub

Abstract: An efficient ultrasound-promoted one-pot three-component synthesis of a series of new 1,2,3-triazole-linked tetrahydrobenzo[b]pyran derivatives as antifungal and antioxidant agents using NaHCO3 has been described for the first time. T

In search of new generation of triazole based antifungal agents, synthesis of series of new 1,2,3-triazolyl pyrano[2,3-c]pyrazoles under ultrasonic irradiation using NaHCO3 has been reported. The bioevaluation results indicate that, the compoun

A facile, one-pot synthesis strategy for the tertiary arylamines bearing N,N-bis(1,2,3-triazol-4-yl)methyl structure has been developed by sequential diprop-2-ynylation of primary amines with propargyl bromide in the presence of calcium hydride in DMF and [3 + 2] “click” cycloaddition with organic azides promoted by cupric acetate in the mixed DMF-H2O media. This protocol provides some features, such as high efficiency and regioselectivity, easy operation, and moderate to good product yield (56–84%) with a wide substrate scope under mild conditions.

FMS-like tyrosine kinase 3 (FLT3) was an important therapeutic target in acute myeloid leukemia (AML). We synthesized two series of 4-((6,7-dimethoxyquinoline-4-yl)oxy)aniline derivatives possessing the semicarbazide moiety and 2,2,2-trifluoro-N,N′-dimeth

Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole as A-region and triazole as B-region. The SAR analysis indicated that 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed better potency compared to the corresponding dihydroindole analogues. Optimization of this design led to the eventual identification of 2-((1-(2-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (6g), a potent TRPV1 antagonist. In vitro, using cells expressing recombinant human TRPV1 channels, 6g displayed potent antagonism activated by capsaicin (IC50 = 0.075 μM) and only partially blocked acid activation of TRPV1. In vivo, 6g exhibited good efficacy in capsaicin-induced and heat-induced pain models and had almost no hyperthermia side-effect. Furthermore, pharmacokinetic studies revealed that compound 6g had a superior oral exposure after oral administration in rats. To understand its binding interactions with the receptor, the docking study of 6g was performed in rTRPV1 model and showed an excellent fit to the binding site. On the basis of its superior profiles, 6g could be considered as the lead candidate for the further development of antinociceptive drugs.

Amyloid beta (Aβ) peptide aggregation is considered as one of the key hallmarks of Alzheimer's disease (AD). Moreover, Aβ peptide aggregation increases considerably in the presence of metal ions and triggers the generation of reactive oxygen species (ROS)

Six series of (+)-usnic acid derivatives were synthesized. The IC50 values of these compounds were determined in T. gondii infected HeLa cells (μM) and in HeLa cells (μM), and their selectivity indexes (SI) were calculated. In vitro, most of th

Efficient formation of water- and air-stable aza-ylides has been achieved using the Staudinger reaction between electron-deficient aromatic azides such as 2,6-dichlorophenyl azide and triarylphosphines. The reaction proceeds rapidly and has been successfully applied to chemical modification of proteins in living cells.

We describe the synthesis of novel triazole-incorporated diindolylmethanes (DIMs) using a molecular hybridization approach. The in vitro antitubercular activity of the DIMs against Mycobacterium tuberculosis H37Ra (ATCC 25177) was tested in the active and

Chemical probes of microRNA (miRNA) function are potential tools for understanding miRNA biology that also provide new approaches for discovering therapeutics for miRNA-associated diseases. MicroRNA-21 (miR-21) is an oncogenic miRNA that is overexpressed in most cancers and has been strongly associated with driving chemoresistance in cancers such as renal cell carcinoma (RCC). Using a cell-based luciferase reporter assay to screen small molecules, we identified a novel inhibitor of miR-21 function. Following structure-activity relationship studies, an optimized lead compound demonstrated cytotoxicity in several cancer cell lines. In a chemoresistant-RCC cell line, inhibition of miR-21 via small molecule treatment rescued the expression of tumor-suppressor proteins and sensitized cells to topotecan-induced apoptosis. This resulted in a >10-fold improvement in topotecan activity in cell viability and clonogenic assays. Overall, this work reports a novel small molecule inhibitor for perturbing miR-21 function and demonstrates an approach to enhancing the potency of chemotherapeutics specifically for cancers derived from oncomir addiction.

The aim of the present study was to determine the cytotoxic effects of a series of novel dehydroepiandrosterone derivatives containing triazole at the C16 position on human cancer cells. The cancer cells used in the present study were A549, Hel

Abstract: The synthesis of a new series of triazole-biscoumarin conjugates by using a molecular hybridization approach is described. The newly synthesized compounds 6a–k were evaluated for their in vitro antitubercular activity against active and dormant

The present study describes the synthesis of 1,2,3-triazole-quinazolinone conjugates (5a-q) from ethyl 4-oxo-3-(prop-2-ynyl)-3,4-dihydroquinazoline-2-carboxylate and phenyl azide/substituted phenyl azides employing Cu(i) catalysed Huisgen 1,3-dipolar cycloaddition. The corresponding acids (6a-q) were obtained by hydrolysis of esters (5a-q) to study the effect of these functionalities on the biological activity. All synthesized compounds were screened for in vitro anticandidal evaluation against Candia albicans, Candida glabrata and Candida tropicalis strains. The results indicated that compound 5n showed potent anticandidal activity with IC50 in the range of 8.4 to 14.6 μg mL?1. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed the non-toxic nature of the selected compounds. Growth kinetic study with compound 5n showed its fungicidal nature as no significant growth of Candida cells was observed even after 24 h. Cellular ergosterol content was determined in the presence of different concentrations of 5n to measure the activity of lanosterol 14α-demethylase indirectly. The results showed significant disruption of the ergosterol biosynthetic pathway through inhibition of lanosterol 14α-demethylase activity supported by docking studies (PDB: 5v5z). Overall, this study demonstrates the anticandidal potential of 5n which can serve as the lead for further structural optimization and SAR studies.

A new series of coumarin-1,2,3-triazole conjugates with varied alkyl, phenyl and heterocycle moieties at C-4 of the triazole nucleus were synthesized using a copper(I)-catalysed Huisgen 1,3-dipolar cycloaddition reaction of corresponding O-propargylated coumarin (3) or N-propargylated coumarin (6) with alkyl or aryl azides. Based on their minimal inhibitory concentrations (MICs) against selected microorganisms, six out of twenty-six compounds showed significant antibacterial activity towards Enterococcus faecalis (MIC = 12.5–50 μg/mL). Moreover, the synthesized triazoles show relatively low toxicity against human erythrocytes.

A highly efficient catalytic system, CuSO4·5H2O/1-(4-methoxyphenyl)-3-phenylthiourea, for the copper(I)-catalyzed azide–alkyne cycloaddition reaction (CuAAC) was discovered. In the above catalytic system, substituted thiourea acts both as a reductant and a ligand. CuSO4·5H2O/1-(4-methoxyphenyl)-3-phenylthiourea is both an economical and efficient catalyst for the CuAAC reaction. In addition, the new catalytic system has advantageous features including mild and green reaction conditions, and broad substrate compatibility. A variety of 1,4-disubstituted 1,2,3-triazoles have been prepared with good to excellent yields with the CuSO4·5H2O/1-(4-methoxyphenyl)-3-phenylthiourea catalytic system in aqueous solution.

A series of new 1,2,3-triazole derivatives have been prepared and screened for their antifungal activity against phytopathogenic fungi using the mycelium growth inhibition method in?vitro. The results indicated that the 1,2,3-triazole hydrazide scaffold d

Diosgenin, a promising anticancer steroidal sapogenin, was isolated from Dioscorea deltoidea. Keeping its stereochemistry rich architecture intact, a scheme for the synthesis of novel diosgenin analogues was designed using Cu (I)-catalysed alkyne-azide cy

Using a click chemistry approach, a series of gallic-acid-1-phenyl-1H-[1,2,3]triazol-4-ylmethyl esters was synthesized to develop more effective antioxidants. The results of DPPH screening indicate that few of the synthesized analogs display better antioxidant effect compared to the standards. Among all, compounds, 9 and 20 displayed highest DPPH radical scavenging effect with IC50 values as low as 6.4±0.2 and 7.9±0.4 μM respectively, compared to the standard ascorbic acid (IC50=12±0.8 μM) and gallic acid (IC50=9.0±0.6 μM). Compound 10 also displayed a potent antioxidant effect with IC50 of 10.80±0.4 μM. This study provides an important aspect with regard to the use of these gallic-acid based synthetic antioxidants in food industry as dietary supplements.