Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Design, synthesis and antitumour activity evaluation of novel dolutegravir derivatives.

ABSTRACT: Based on the modification of the structure of dolutegravir, we introduced 1,2,3-triazole moieties with different substituted groups and obtained a lot of novel dolutegravir derivatives. The activity of A549 cells treated with the derivatives was examined, and most compounds showed good inhibitory effects. Among them, compounds 4b and 4g were the most effective, and inhibited the growth of A549 cells with IC₅₀ values of 8.72 ± 0.11 μM and 12.97 ± 0.32 μM, respectively. In addition, compound 4g induced apoptosis and clonal suppression in A549 tumor cells. Compound 4g also activated the LC3 signaling pathway to induce autophagy in tumor cells, and activated the γ-H2AX signaling pathway to induce DNA damage in tumor cells.

SUBMITTER: Hou XX

PROVIDER: S-EPMC10440426 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Design, synthesis and antitumour activity evaluation of novel dolutegravir derivatives.

Hou Xi-Xi XX Mao Long-Fei LF Guo Yajie Y Lou Chaoxuan C Wang Lan L Li Rui-Fang RF Wang Huili H Li San-Qiang SQ Yang Jian-Xue JX

Frontiers in pharmacology 20230807

Based on the modification of the structure of dolutegravir, we introduced 1,2,3-triazole moieties with different substituted groups and obtained a lot of novel dolutegravir derivatives. The activity of A549 cells treated with the derivatives was examined, and most compounds showed good inhibitory effects. Among them, compounds 4b and 4g were the most effective, and inhibited the growth of A549 cells with IC50 values of 8.72 ± 0.11 μM and 12.97 ± 0.32 μM, respectively. In ...[more]

PMID: 37608893

Similar Datasets

Design, Synthesis, and Herbicidal Activity Evaluation of Novel Aryl-Naphthyl Methanone Derivatives.

Project description:4-Hydroxyphenylpyruvate dioxygenase (HPPD) is one of the most vital targets for herbicides discovery. In search for HPPD inhibitors with novel scaffolds, a series of aryl-naphthyl methanone derivatives have been designed and synthesized through alkylation and Friedel-Crafts acylation reactions. The bioassay indicated some of these compounds displayed preferable herbicidal activity at the rate of 0.75 mmol/m2 by post-emergence application, in which compound 3h displayed the best herbicidal activity. The molecular docking showed that compound 3h could bind well to the active site of the AtHPPD. This study shows that aryl-naphthyl methanone derivatives could be a potential lead structure for further development of novel herbicides.

| S-EPMC6349756 | biostudies-literature

Design and synthesis of phenylthiophosphoryl dichloride derivatives and evaluation of their antitumour and anti-inflammatory activities.

Project description:Tumours and inflammation are serious risks to human health and are importantly regulated by the gas signalling molecule hydrogen sulphide. In this work, we report the rational design and synthesis of H2S donor molecules based on phenylthiophosphoryl dichloride nuclei and assess their efficacy against tumours and inflammation. We predicted its potential anticancer targets based on network pharmacology and then verified the inhibitory effect of the active compound S11 on the pathway PI3K/AKT by enzyme inhibition and molecular docking assay. In addition, compound S11 exhibited a potent anti-inflammatory effect on macrophages, effectively reducing the levels of inflammatory mediators TNF-α, IL-10 and HO-1. Compound S11 can be used as a new chemical entity for the discovery of new anti-cancer drugs or anti-inflammatory drugs.

| S-EPMC11790660 | biostudies-literature

Design, synthesis, and insecticidal activity evaluation of piperine derivatives.

Project description:Structural optimization of natural products has become one of the most effective ways to develop novel pesticides. In this study, 30 novel pesticide derivatives containing a linear bisamide were synthesized. Then, their insecticidal activities against P. xylostella were evaluated. Results indicate that different bisamide substitutes show different larvicidal structure-activity relationships. At the same time, 2-trifluoroethyl is the most efficient substituent. The bioactivity results showed that most of the desired compounds exhibited better insecticidal activity against P. xylostella than piperine. Among them, compound D28 resulted in 90% mortality at 1 mg/ml concentration. This study provides a novel protocol for the discovery of new insecticides. The molecular docking results indicated that compound D28 could act on γ-aminobutyric acid receptors.

| S-EPMC9360595 | 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

Design, Synthesis, and Antitumor Activity of Novel Quinazoline Derivatives.

Project description:In an attempt to explore a new class of epidermal growth factor receptor (EGFR) inhibitors, novel 4-stilbenylamino quinazoline derivatives were synthesized through a Dimorth rearrangement reaction and characterized via IR, ¹H-NMR, 13C-NMR, and HRMS. Methoxyl, methyl, halogen, and trifluoromethyl groups on stilbeneamino were detected. These synthesized compounds were evaluated for antitumor activity in vitro against eight human tumor cell lines with an MTS assay. Most synthesized compounds exhibited more potent activity (IC50 = ~2.0 ?M) than gefitinib (IC50 > 10.0 ?M) against the A431, A549, and BGC-823 cell lines. Docking methodology of compound 6c and 6i binding into the ATP site of EGFR was carried out. The results showed that fluorine and trifluoromethyl played an important role in efficient cell activity.

| S-EPMC6151509 | biostudies-literature

Design, synthesis and insecticidal activity of novel phenylurea derivatives.

Project description:A series of novel phenylurea derivatives were designed and synthesized according to the method of active groups linkage and the principle of aromatic groups bioisosterism in this study. The structures of the novel phenylurea derivatives were confirmed based on ESI-MS, IR and 1H-NMR spectral data. All of the compounds were evaluated for the insecticidal activity against the third instars larvae of Spodoptera exigua Hiibner, Plutella xyllostella Linnaeus, Helicoverpa armigera Hubner and Pieris rapae Linne respectively, at the concentration of 10 mg/L. The results showed that all of the derivatives displayed strong insecticidal activity. Most of the compounds presented higher insecticidal activity against S. exigua than the reference compounds tebufenozide, chlorbenzuron and metaflumizone. Among the synthesized compounds, 3b, 3d, 3f, 4b and 4g displayed broad spectrum insecticidal activity.

| S-EPMC6272132 | biostudies-literature

Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity.

Project description:A series of novel carnosic acid 1 derivatives incorporating urea moieties at the C-20 position was synthesized and evaluated for their antiproliferative activity against the HCT116 colorectal cancer cell line. Most derivatives demonstrated enhanced antiproliferative activity compared to that of carnosic acid 1. The most promising derivatives were tested in other colorectal cancer cell lines (SW480, SW620, and Caco-2), melanoma (A375), and pancreatic cancer (MiaPaca-2). Derivative 14 consistently demonstrated the highest activity across all tested cancer cell lines, showing selectivity for cancer cells over normal cells. Further investigation of the mechanism of action in SW480 cells revealed that compound 14 induced cell cycle arrest at the G0/G1 phase by downregulating CDK4 and CDK6. Molecular docking studies revealed that compound 14 established several interactions with key residues in the active site of CDK6. Additionally, compound 14 also reduced ROS production. In summary, our results strongly indicate that compound 14 has potential as a lead compound in the development of innovative anticancer drugs.

| S-EPMC11728001 | biostudies-literature

Design and Synthesis of Novel Chalcone Derivatives: Anti-Breast Cancer Activity Evaluation and Docking Study.

Project description:Chalcone is a common simple fragment of natural products with anticancer activity. In a previous study, the research group discovered a series of chalcone derivatives with stronger anticancer activities. To find better anticancer drugs, novel chalcone derivatives A1-A14, B1-B14 have continuously been designed and synthesized. The antiproliferative activity of these compounds against breast cancer cells (MCF-7) was investigated by the Cell Counting Kit-8 (CCK-8) method with 5-fluorouracil (5-Fu) as the control drug. The results showed that compound A14 exhibited excellent antiproliferative ability compared to the control drug 5-Fu. Scratch experiments and cloning experiments further confirmed that compound A14 could inhibit the proliferation and colony formation activity of MCF-7 cells. In addition, molecular docking primarily explains the interaction between compound and protein. These results suggested that compound A14 could be a promising chalcone derivative for further anti-breast cancer research.

| S-EPMC10649752 | biostudies-literature

Design, synthesis and activity evaluation of arctigenin derivatives with HDAC inhibition activity.

Project description:Arctigenin, a natural product with diverse pharmacological activities, can inhibit cell proliferation and survival and has shown promising potential in cancer research. In this study, we designed a series of arctigenin derivatives with HDAC inhibitory activity based on the synergistic effects between HDAC inhibitors and arctigenin. Among them, compound B7 exhibited significantly higher antiproliferative activity in the MV411 cell line compared to the positive control, tucidinostat. Additionally, enzymatic activity testing was performed with compound B7. Further mechanistic studies indicated that compound B7 induced apoptosis through the Caspase-3 pathway in MV411 cells and enhanced histone acetylation levels in the MV411 cell line. These findings highlight the broad potential application of these arctigenin derivatives in cancer therapy.

| S-EPMC10951978 | biostudies-literature

Design, synthesis and biological evaluation of novel betulinic acid derivatives.

Project description:UnlabelledBackgroundTumor, is one of the major reason for human death, due to its widespread occurrence. Betulinic acid derivatives have attracted considerable attention as cancer chemopreventive agents and also as cancer therapeutics. Many of its derivatives inhibit the growth of human cancer cell lines by triggering apoptosis. With this background, we planned to synthesize a series of betulinic acid derivatives to assess their antiproliferation efficacy on human cancer cell lines.ResultsA series of novel betulinic acid derivatives were designed and synthesized as highlighted by the preliminary antitumor evaluation against MGC-803, PC3, A375, Bcap-37 and A431 human cancer cell lines in vitro. The pharmacological results showed that some of the compounds displayed moderate to high levels of antitumor activities with most of new exhibiting higher inhibitory activities compared to BA. The IC50 values of compound 3c on the five cancer cell lines were 2.3, 4.6, 3.3, 3.6, and 4.3 μM, respectively. Subsequent fluorescence staining and flow cytometry analysis (FCM) indicated that compound 3c could induce apoptosis in MGC-803 and PC3 cell lines, and the apoptosis ratios reached the peak (37.38% and 33.74%) after 36 h of treatment at 10 μM.ConclusionsThis study suggests that most of betulinic acid derivatives could inhibit the growth of human cancer cell lines. Furthermore, compound 3c could induce apoptosis of cancer cells.

| S-EPMC3541990 | 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