Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Design, Synthesis, and the Biological Evaluation of a New Series of Acyclic 1,2,3-Triazole Nucleosides.

ABSTRACT: A new strategy for the synthesis of N³ -benzoylated- and N³ -benzylated N¹ -propargylquinazoline-2,4-diones 30a-d and 31a-d from isatoic anhydride 41 is reported. The alkynes 30a-d and 31a-d were applied in the 1,3-dipolar cycloadditions with azides 27 and 28 to synthesize acyclic 1,2,3-triazole nucleosides. The obtained alkynes and 1,2,3-triazole were evaluated for antiviral activity against a broad range of DNA and RNA viruses. The alkyne 30d showed activity against adenovirus-2 (EC₅₀ = 8.3 μM), while compounds 37a and 37d were also active toward herpes simplex virus-1 wild-type and thymidine kinase deficient (HSV-1 TK^- ) strains (EC₅₀ values in the range of 4.6-13.8 μM). In addition, compounds 30a, 30b, 37b, and 37c exhibited activity toward varicella-zoster virus (VZV) TK⁺ and TK^- strains (EC₅₀ = 2.1-9.5 μM). The compound 30b proved to be the most selective against VZV and displayed marginal activity against human cytomegalovirus (HCMV). Although the compound 30a had improved anti-HCMV activity, the increase in anti-HCMV activity was accompanied by significant toxicity. Compounds 37a and 37d showed inhibitory effects toward the human T lymphocyte (CEM) cell line (IC₅₀ = 21 ± 7 and 22 ± 1 μM, respectively), while compound 35 exhibited cytostatic activity toward HMEC-1 cells (IC₅₀ = 28 ± 2 μM).

SUBMITTER: Glowacka IE

PROVIDER: S-EPMC7161868 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Design, Synthesis, and Biological Evaluation of Desmuramyl Dipeptides Modified by Adamantyl-1,2,3-triazole.

Project description:Muramyl dipeptide (MDP) is the smallest peptidoglycan fragment able to trigger the immune response. Structural modification of MDP can lead to the preparation of analogs with improved immunostimulant properties, including desmuramyl peptides (DMPs). The aim of this work was to prepare the desmuramyl peptide (L-Ala-D-Glu)-containing adamantyl-triazole moiety and its mannosylated derivative in order to study their immunomodulatory activities in vivo. The adjuvant activity of the prepared compounds was evaluated in a murine model using ovalbumin as an antigen, and compared to the reference adjuvant ManAdDMP. The results showed that the introduction of the lipophilic adamantyl-triazole moiety at the C-terminus of L-Ala-D-Glu contributes to the immunostimulant activity of DMP, and that mannosylation of DMP modified with adamantyl-triazole causes the amplification of its immunostimulant activity.

| S-EPMC8587862 | biostudies-literature

Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives as potent cholinesterase inhibitors.

Project description:We report herein the design and synthesis of a series of 11 novel tacrine-1,2,3-triazole derivatives via a Cu(i)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction. The newly synthesized compounds were evaluated for their inhibition activity against Electrophorus electricus acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) as potential drug targets for Alzheimer's disease (AD). Among the designed compounds, compound 8a2 exhibited potent inhibition against AChE and BChE with IC50 values of 4.89 μM and 3.61 μM, respectively. Further structure-activity relationship (SAR) and molecular modeling studies may provide valuable insights into the design of better tacrine-triazole analogues with potential therapeutic applications for AD.

| S-EPMC6071962 | biostudies-literature

Novel Double-Modified Colchicine Derivatives Bearing 1,2,3-Triazole: Design, Synthesis, and Biological Activity Evaluation.

Project description:A series of 1,4-disubstituted 1,2,3-triazoles having 10-demethoxy-10-N-methylaminocolchicine core were designed and synthesized via the Cu(I)-catalyzed "click" reaction and screened for their in vitro cytotoxicity against four cancer cell lines (A549, MCF-7, LoVo, LoVo/DX) and one noncancerous cell line (BALB/3T3). Indexes of resistance (RI) and selectivity (SI) were also determined to assess the potential of the analogues to break drug resistance of the LoVo/DX cells and to verify their selectivity toward killing cancer cells over normal cells. The compounds with an ester or amide moiety in the fourth position of 1,2,3-triazole of 10-N-methylaminocolchicine turned out to have the greatest therapeutic potential (low IC50 values and favorable SI values), much better than that of unmodified colchicine or doxorubicin and cisplatin. Thus, they make a valuable clue for the further search for a drug having a colchicine scaffold.

| S-EPMC8515607 | biostudies-literature

Synthesis and biological evaluation of benzimidazole-linked 1,2,3-triazole congeners as agents.

Project description:BackgroundBenzimidazoles and triazoles are useful structures for research and development of new pharmaceutical molecules and have received much attention in the last decade because of their highly potent medicinal activities.FindingsA simple and efficient synthesis of triazole was carried out by treatment of 2-(4-azidophenyl)-1H-benzo[d]imidazole (6) with different types of terminal alkynes in t-BuOH/H2O, sodium ascorbate, and Zn(OTf)2, screened for cytotoxicity assay and achieved good results. A series of new benzimidazole-linked 1,2,3-triazole (8a-i) congeners were synthesized through cyclization of terminal alkynes and azide. These synthesized congeners 8a-i were evaluated for their cytotoxicity against five human cancer cell lines. These benzimidazole-linked 1,2,3-triazole derivatives have shown promising activity with IC50 values ranging from 0.1 to 43 μM. Among them, the compounds (8a, 8b, 8c, and 8e) showed comparable cytotoxicity with adriamycin control drug.ConclusionsIn conclusion, we have developed a simple, convenient, and an efficient convergent approach for the synthesis of benzimidazole-linked 1,2,3-triazole congeners as agents. Graphical Abstract Synthesis of 1,2,3-triazole derivatives.

| S-EPMC4970438 | biostudies-literature

New 1,2,3-Triazole/1,2,4-triazole Hybrids as Aromatase Inhibitors: Design, Synthesis, and Apoptotic Antiproliferative Activity.

Project description:A novel series of 1,2,3-triazole/1,2,4-triazole hybrids 5a, 5b, and 6a-i was designed and synthesized as antiproliferative agents targeting aromatase enzymes. The antiproliferative activity of the new hybrids against four cancer cells was studied using Erlotinib as a control. Compounds 6a and 6b demonstrated the highest antiproliferative activity among these hybrids, with GI50 values of 40 nM and 35 nM, respectively. Compound 6b was the most potent derivative, with a GI50 of 35 nM, comparable to Erlotinib's GI50 of 33 nM. Compound 6b inhibited all cancer cell lines with comparable efficacy to Erlotinib. Compounds 5a, 5b, and 6a-i were tested for inhibitory action against aromatase as a potential target for their antiproliferative activity. Results revealed that compounds 6a and 6b were the most potent aromatase inhibitors, with IC50 values of 0.12 ± 0.01 µM and 0.09 ± 0.01 µM, respectively, being more potent than the reference Ketoconazole (IC50 = 2.6 ± 0.20 µM) but less potent than Letrozole (IC50 = 0.002 ± 0.0002). These findings indicated that compounds 6a and 6b had significant aromatase inhibitory action and are potential antiproliferative candidates. The findings were further linked to molecular docking investigations, which gave models of strong interactions with the aromatase domain for inhibitors with high binding scores.

| S-EPMC10609154 | biostudies-literature

1,2,3-Triazole-fused spirochromenes as potential anti-tubercular agents: synthesis and biological evaluation.

Project description:A facile and convenient approach has been designed for the synthesis of novel prototypes that possess the advantage of the two pharmacophores of chromene and 1,2,3-triazole in a single molecular backbone, were evaluated against Mycobacterium tuberculosis H37Rv strain. The new analogues 1,2,3-triazole-fused spirochromenes were accomplished in four step synthetic strategy utilizing click chemistry ([3 + 2] Huisgen cycloaddition) in the ultimate step. The synthesized compounds were established based on the spectral data and X-ray crystal structure for 7a. Among the compounds tested against Mycobacterium tuberculosis H37Rv strain, some products exhibited potent antimycobacterial activity with minimum inhibitory concentration (MIC) values ranging from 1.56 to 6.25 μg mL-1. Compounds exhibiting good in vitro potency in the MTB MIC assay were further examined for cytotoxicity in a RAW 264.7 cells. Compounds 7a, 7d, 7i (MIC: 1.56 μg mL-1) and 7k, 7m (MIC: 3.125 μg mL-1) exhibited promising hits.

| S-EPMC9080333 | biostudies-literature

Synthesis and biological evaluation of selective phosphonate-bearing 1,2,3-triazole-linked sialyltransferase inhibitors.

Project description:The critical role of sialyltransferase (ST) enzymes in tumour cell growth and metastasis, as well as links to multi-drug and radiation resistance, has seen STs emerge as a target for potential antimetastatic cancer treatments. One promising class of ST inhibitors that improve upon the pharmacokinetic issues of previous inhibitors is the 1,2,3-triazole-linked transition-state analogues. Herein, we present the design and synthesis of a new generation of 1,2,3-triazole-linked sialyltransferase inhibitors, along with their biological evaluation demonstrating increased potency for phosphonate bearing compounds. The six most promising inhibitors presented in this work exhibited a greater number of binding modes for hST6Gal I over hST3Gal I, with K i ranging from 3-55 μM. This work highlights phosphonate bearing triazole-linked compounds as a promising class of synthetically accessible ST inhibitors that warrant further investigation.

| S-EPMC8528205 | biostudies-literature

Design, Synthesis, and Biological Evaluation of Pyridineamide Derivatives Containing a 1,2,3-Triazole Fragment as Type II c-Met Inhibitors.

Project description:A series of 4-(pyridin-4-yloxy)benzamide derivatives containing a 1,2,3-triazole fragment were designed, synthesized, and their inhibitory activity against A549, HeLa, and MCF-7 cancer cell lines was evaluated. Most compounds exhibited moderate to potent antitumor activity against the three cell lines. Among them, the promising compound B26 showed stronger inhibitory activity than Golvatinib, with IC50 values of 3.22, 4.33, and 5.82 μM against A549, HeLa, and MCF-7 cell lines, respectively. The structure-activity relationships (SARs) demonstrated that the modification of the terminal benzene ring with a single electron-withdrawing substituent (fluorine atom) and the introduction of a pyridine amide chain with a strong hydrophilic group (morpholine) to the hinge region greatly improved the antitumor activity. Meanwhile, the optimal compound B26 showed potent biological activity in some pharmacological experiments in vitro, such as cell morphology study, dose-dependent test, kinase activity assay, and cell cycle experiment. Finally, the molecular docking simulation was performed to further explore the binding mode of compound B26 with c-Met.

| S-EPMC6983042 | biostudies-literature

The synthesis, antiviral, cytostatic and cytotoxic evaluation of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker.

Project description:The efficient synthesis of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker is described starting from diethyl azidomethyl-, 2-azidoethyl-, 3-azidopropyl-, 4-azidobutyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropyl- and 3-azido-1-hydroxypropylphosphonates and selected alkynes under microwave irradiation. Several O,O-diethylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses and cytostatic activity against murine leukaemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Acyclonucleotide 22e exhibited activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC?? = 17 ?M) and feline herpes virus (EC?? = 24 ?M) in CRFK cell cultures, while compounds 20k, 21k, 22k and 23k preferentially inhibited proliferation of human T-lymphocyte CEM cells at IC?? in the 2.8-12 ?M range.

| S-EPMC7115586 | biostudies-literature

Synthesis and biological evaluation of ciprofloxacin - 1,2,3-triazole hybrids as antitumor, antibacterial, and antioxidant agents.

Project description:Six novel ciprofloxacin-1,2,3-triazole hybrids (6a-f) were synthesized via click reaction, by reacting of methyl 1-cyclopropyl-6-fluoro-4-oxo-7-(4-(3-oxobutanoyl)piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate (5) with various aryl azides (9a-f). The new compounds were characterized using High-Resolution Mass Spectrometry (HRMS), 1H NMR, 13C NMR, and elemental analysis. Compounds (6a-f) screened for their in vitro anticancer activity against three cell lines, namely, non-small cell lung cancer (A549), glioblastoma (U-87 MG), and breast cancer (MCF7). Hybrids 6a and 6b exhibited remarkable anti-proliferative activity against all three cell-lines. IC50 values of 6b for all cancer cell lines were significantly lower comparing to the standard reference compound IC50. The IC50 of 6b for the normal cell (HDF) line was significantly higher than the reported for cisplatin [IC50 = 170.7 ± 8.1 μM/ml (HDF), (p ≤ 0.001)], indicating less toxicity towards normal cells and thereby has a better therapeutic index, with a selectivity index of 142.3 for U87 cell line. Compounds 6e, 6d, and 6f displayed significant cytotoxic activity against only U-87 and MCF-7 cancer cell lines, compared to normal cells (HDF). Compound 6f [IC50 = 7.9 ± 2.3 μM/ml (U-87) and 10.6 ± 3 μM/ml (MCF-7)] was more potent than cisplatin [IC50 = 28.3 ± 5.3 μM/ml (U-87) and 26.9 ± 4.7 μM/ml (MCF-7)] in displaying anti-proliferative effect against U-87 and MCF-7 cells, with less cytotoxic to normal cells [IC50 = 141.7 ± 4.1] than cisplatin [IC50 = 40.9 ± 5.4]. Moreover, they were tested for their antioxidant activity in DPPH and ABTS assays and antibacterial activity.

| S-EPMC10731006 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data