Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Design, synthesis and biological evaluation of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives as antiglioma agents.

ABSTRACT: d-2-Hydroxyglutarate (d-2HG) is frequently found in human brain cancers. Approximately 50-80% of grade II glioma patients have a high level of d-2HG production, which can lead to cancer initiation. In this study, a series of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives were designed and synthesized as antiglioma agents, and their related structure-activity relationships are discussed. Among these novel compounds, 4a exhibited promising anti-proliferative activity against glioma HT1080 cells and U87 cells with an IC₅₀ of 1.43 ?M and 4.6 ?M, respectively. Further studies found that the most active compound (4a) shows an 86.3% inhibitory rate against the intracellular production of d-2HG at 1 ?M, and dramatic inhibitory effects, even at 1 ?M on the colony formation and migration of U87 and HT1080 cells.

SUBMITTER: Li YB

PROVIDER: S-EPMC6071749 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Design, synthesis and biological evaluation of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives as antiglioma agents.

Li Yi-Bin YB Hou Wen W Lin Hui H Sun Ping-Hua PH Lin Jing J Chen Wei-Min WM

MedChemComm 20180119 3

d-2-Hydroxyglutarate (d-2HG) is frequently found in human brain cancers. Approximately 50-80% of grade II glioma patients have a high level of d-2HG production, which can lead to cancer initiation. In this study, a series of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives were designed and synthesized as antiglioma agents, and their related structure-activity relationships are discussed. Among these novel compounds, 4a exhibited promising anti-proliferative activity against gli ...[more]

PMID: 30108937

Similar Datasets

Design of novel 4-hydroxy-chromene-2-one derivatives as antimicrobial agents.

Project description:This paper presents the design of novel 4-hydroxy-chromene-2 one derivatives, based on previously obtained minimal inhibitory concentration values (MICs), against twenty four microorganism cultures, gram positive and negative bacteria and fungi. Two of our compounds, 3b (MIC range 130-500 microg/mL) and 9c (31.25-62.5 microg/mL), presented high potential antimicrobial activity. The compound 9c had equal activity to the standard ketoconazole (31.25 microg/mL) against M. mucedo. Enlarged resistance of S. aureus, E. coli and C. albicans on the effect of potential drugs and known toxicity of coumarin antibiotics, motivated us to establish SAR and QSAR models of activity against these cultures and correlate biological activity, molecular descriptors and partial charges of functional groups to explain activity and use for the design of new compounds. The QSAR study presents essential relation of antimicrobial activity and dominant substituents, 4-hydroxy, 3-acetyl and thiazole functional groups, also confirmed through molecular docking. The result was ten new designed compounds with much improved predicted inhibition constants and average biological activity.

| S-EPMC6257651 | biostudies-literature

Design, Synthesis, and Biological Evaluation of 3-Substituted-Indolin-2-One Derivatives as Potent Anti-Inflammatory Agents.

Project description:This study aimed to synthesize and evaluate the anti-inflammatory activity of 3-substituted-indolin-2-one derivatives. Cell viability of 3-substituted-indolin-2-one derivatives was measured with the EZ-Cytox reagent; interleukin (IL)-6, tumor necrosis factor (TNF)-α, and inducible NOS mRNA levels were measured using Taqman qRT-PCR; pro-inflammatory cytokine IL-6 and TNF-α levels were determined using ELISA kits; the phosphorylation of Akt, JNK, ERK, p38, p65, and IκB protein levels were measured by immunoblotting. Among the nineteen 3-substituted-indolin-2-one derivatives synthesized, 3-(3-hydroxyphenyl)-indolin-2-one showed the highest anti-inflammatory activity, inhibiting the nitric oxide production related to inflammation, suppressing the production of TNF-α and IL-6 in a concentration-dependent manner and mRNA expression. Moreover, 3-(3-hydroxyphenyl)-indolin-2-one significantly inhibited lipopolysaccharide (LPS)-induced signal pathways such as the Akt, MAPK, and NF-κB signaling pathways. Our findings revealed that a 3-substituted-indolin-2-one derivative, 3-(3-hydroxyphenyl)-indolin-2-one, possesses excellent anti-inflammatory activity and can be considered for future research.

| S-EPMC9916847 | biostudies-literature

Design and Synthesis of Pyrazole-3-one Derivatives as Hypoglycaemic Agents.

Project description:Pyrazole-3-one compounds were designed on the basis of docking studies of previously reported antidiabetic pyrazole compounds. The amino acid residues found during docking studies were used as guidelines for the modification of aromatic substitutions on pyrazole-3-one structure. Depending on the docking score, the designed compounds were selectively prioritized for synthesis. The synthesized compounds were subjected to in vivo hypoglycemic activity using alloxan induced diabetic rats and metformin as a standard. Compound 4 having sulphonamide derivative was found to be the most potent compound among the series.

| S-EPMC4334925 | biostudies-literature

Molecular Design, Synthesis, and Biological Evaluation of 2-Hydroxy-3-Chrysino Dithiocarbamate Derivatives.

Project description:A series of 2-hydroxy-3-chrysino dithiocarbamate derivatives (3a-k) were designed, synthesized, and characterized for their structure determination by 1H NMR, 13C NMR, and HRMS (ESI) spectral data. They were screened for their in vitro biological activities against a panel of selected bacterial and fungal strains. These antimicrobial studies indicate that some of the analogues manifested significant activity compared to standard drugs. Among the synthetic analogues (3a-k), compounds 3d, 3f, and 3j exhibited very good antibacterial activity and compounds 3d, 3f, and 3h showed very good antifungal activity compared to the standard drugs penicillin and itrazole, respectively. The compounds 3e, 3g, and 3h showed moderate antibacterial activity and the compounds 3j and 3k showed moderate antifungal activity. Molecular docking studies were performed and the experimental antimicrobial screening results were also correlated with the binding energy values obtained by molecular docking. The synthesized chrysin analogues (3a-k) have obeyed Lipinski's "rule of five" and have drug-likeness.

| S-EPMC6749404 | biostudies-literature

Design, Synthesis and Biological Evaluation of New Pyrimidine Derivatives as Anticancer Agents.

Project description:Anticancer drug resistance is a challenging phenomenon of growing concern which arises from alteration in drug targets. Despite the fast speed of new chemotherapeutic agent design, the increasing prevalence of this phenomenon requires further research and treatment development. Recently, we reported a new aminopyrimidine compound-namely RDS 344-as a potential innovative anticancer agent. Herein, we report the design, synthesis, and anti-proliferative activity of new aminopyrimidine derivatives structurally related to RDS 3442 obtained by carrying out substitutions at position 6 of the pyrimidine core and/or on the 2-aniline ring of our hit. The ability to inhibit cell proliferation was evaluated on different types of tumors, glioblastoma, triple-negative breast cancer, oral squamous cell carcinomas and colon cancer plus on human dermal fibroblasts chosen as control of normal cells. The most interesting compound was the N-benzyl counterpart of RDS 3442, namely 2a, that induced a significant decrease in cell viability in all the tested tumor cell lines, with EC50s ranging from 4 and 8 μM, 4-13 times more active of hit. These data suggest a potential role for this class of molecules as promising tool for new approaches in treating cancers of different histotype.

| S-EPMC7867324 | biostudies-literature

6-Hydroxy-methyl-4-meth-oxy-2H-pyran-2-one (Opuntiol).

Project description:The title compound, C(7)H(8)O(4), isolated from Opuntia dillenii Haw (Cacta-ceae), is almost planar [maximum deviation of 0.027?(2)?Å] except for the H atoms of the methylene and methyl groups. The crystal packing is stabilized by C-H?O and O-H?O inter-molecular hydrogen bonds, resulting in the formation of a three-dimensional network.

| S-EPMC2980196 | biostudies-other

Design and Synthesis of Novel 1-hydroxy-2,4,5-triaryl Imidazole Derivatives as Anti-cytokine Agents.

Project description:Among recent advances in the identification of anti-inflammation agents, anti-cytokines (like Interleukin-1), related to p38 MAPK families play an important role; Here in we designed new effective and low toxic anti-cytokine agents based on 1-hydroxy-2,4,5-triaryl imidazole derivatives. The reaction of oximoinoketone intermediate with ten different aromatic aldehyde and ammonium acetate in refluxing acetic acid condition give imidazole derived product, the IL-1β inhibitory assay were performed on Human PBMCs (peripheral blood mononuclear cells) using an enzyme-linked immunosorbent assay (ELISA) kit and then in computational part the binding mode of the best compound was accomplished by docking in Crystal structure of p38 MAP kinase (PDB ID: 1A9U) compared with SB202190 as standard drug. All compounds were synthesized and evaluated in biological assay showing the inhibitory activity from 28% to 82% compared to SB202190 and binding mode analysis revealed that the hydrogen-bond interactions with residues (Met109, Val30) were key point in inhibitor binding. Compound 5g clearly proved the best inhibitory action and could be further utilized for designing newer anti-cytokine agents and p38α MAP kinase potentially inhibitory action.

| S-EPMC7462483 | biostudies-literature

Design, synthesis, and biological evaluation of biotinylated colchicine derivatives as potential antitumor agents.

Project description:Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovering new anti-tumour drugs to improve tumour targeting effects and reduce off-target toxicities. Colchicine is one of the most prominent and historically microtubule-targeting drugs, but its clinical applications are hindered by notorious adverse effects. In this study, we presented a novel tumour-specific conjugate 9 that consists of deacetylcolchicine (Deac), biotin, and a cleavable disulphide linker. 9 was found to exhibit potent anti-tumour activity and exerted higher selectivity between tumour and nontarget cells than Deac. The targeting moiety biotin might enhance the transport capability and selectivity of 9 to tumour cells via biotin receptor-mediated endocytosis. The tubulin polymerisation activity of 9 (with DTT) was close to the parent drug Deac. These preliminary results suggested that 9 is a high potency and reduced toxicity antitumor agent and worthy of further investigation.

| S-EPMC8725855 | biostudies-literature

Design, synthesis, and biological evaluation of novel arylcarboxamide derivatives as anti-tubercular agents.

Project description:Our group has previously reported several indolecarboxamides exhibiting potent antitubercular activity. Herein, we rationally designed several arylcarboxamides based on our previously reported homology model and the recently published crystal structure of the mycobacterial membrane protein large 3 (MmpL3). Many analogues showed considerable anti-TB activity against drug-sensitive (DS) Mycobacterium tuberculosis (M. tb) strain. Naphthamide derivatives 13c and 13d were the most active compounds in our study (MIC: 6.55, 7.11 μM, respectively), showing comparable potency to the first line anti-tuberculosis (anti-TB) drug ethambutol (MIC: 4.89 μM). In addition to the naphthamide derivatives, we also identified the quinolone-2-carboxamides and 4-arylthiazole-2-carboxamides as potential MmpL3 inhibitors in which compounds 8i and 18b had MIC values of 9.97 and 9.82 μM, respectively. All four compounds retained their high activity against multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tb strains. It is worth noting that the two most active compounds 13c and 13d also exhibited the highest selective activity towards DS, MDR and XDR M. tb strains over mammalian cells [IC50 (Vero cells) ≥ 227 μM], indicating their potential lack of cytotoxicity. The four compounds were docked into the MmpL3 active site and were studied for their drug-likeness using Lipinski's rule of five.

| S-EPMC7497412 | biostudies-literature

Novel Pyridothienopyrimidine Derivatives: Design, Synthesis and Biological Evaluation as Antimicrobial and Anticancer Agents.

Project description:The growing risk of antimicrobial resistance besides the continuous increase in the number of cancer patients represents a great threat to global health, which requires intensified efforts to discover new bioactive compounds to use as antimicrobial and anticancer agents. Thus, a new set of pyridothienopyrimidine derivatives 2a,b-9a,b was synthesized via cyclization reactions of 3-amino-thieno[2,3-b]pyridine-2-carboxamides 1a,b with different reagents. All new compounds were evaluated against five bacterial and five fungal strains. Many of the target compounds showed significant antimicrobial activity. In addition, the new derivatives were further subjected to cytotoxicity evaluation against HepG-2 and MCF-7 cancer cell lines. The most potent cytotoxic candidates (3a, 4a, 5a, 6b, 8b and 9b) were examined as EGFR kinase inhibitors. Molecular docking study was also performed to explore the binding modes of these derivatives at the active site of EGFR-PK. Compounds 3a, 5a and 9b displayed broad spectrum antimicrobial activity with MIC ranges of 4-16 µg/mL and potent cytotoxic activity with IC50 ranges of 1.17-2.79 µM. In addition, they provided suppressing activity against EGFR with IC50 ranges of 7.27-17.29 nM, higher than that of erlotinib, IC50 = 27.01 nM.

| S-EPMC8839448 | biostudies-literature