Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and biological evaluation of novel N-methyl-picolinamide-4-thiol derivatives as potential antitumor agents.

ABSTRACT: A novel series of N-methylpicolinamide-4-thiol derivatives were synthesized and evaluated on human cancer cell lines. Among them, compound 6p displayed potent and broad-spectrum anti-proliferative activities in vitro on some human cancer cell lines, even better than sorafenib. The advanced kinase inhibitory assays showed that compound 6p could selectively inhibit Aurora-B kinase. The biological results were rationalized by the molecular docking study, which indicated the stable interactions of 6p with the Aurora-B kinase.

SUBMITTER: Huang TT

PROVIDER: S-EPMC6268926 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and biological evaluation of novel N-methyl-picolinamide-4-thiol derivatives as potential antitumor agents.

Huang Ting-Ting TT Huang Yun-Chuang YC Qing Xiao-Yu XY Xia Yong Y Luo Xun X Ye Ting-Hong TH Yu Luo-Ting LT

Molecules (Basel, Switzerland) 20120525 6

A novel series of N-methylpicolinamide-4-thiol derivatives were synthesized and evaluated on human cancer cell lines. Among them, compound 6p displayed potent and broad-spectrum anti-proliferative activities in vitro on some human cancer cell lines, even better than sorafenib. The advanced kinase inhibitory assays showed that compound 6p could selectively inhibit Aurora-B kinase. The biological results were rationalized by the molecular docking study, which indicated the stable interactions of 6 ...[more]

PMID: 22634842

Similar Datasets

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 Biotinylated Podophyllotoxin Derivatives as Potential Antitumor Agents.

Project description:Podophyllotoxin has long been used as an active substance for cytotoxic activity. Fourteen novel biotinylated podophyllotoxin derivatives were designed, synthesized, and evaluated for cytotoxic activity for this study. The synthesized compounds were evaluated for cytotoxic activity in the following human cancer cell lines, SW480, MCF-7, A-549, SMMC-7721, and HL-60 by MTT assay. Most of them exhibited potent cytotoxic effects and compound 15 showed the highest cytotoxic activity among the five cancer cell lines tested, having its IC50 values in the range of 0.13 to 0.84 ?M. Apoptosis analysis revealed that compound 15 caused obvious induction of cell apoptosis. Compound 15 significantly down-regulated the expression level of the marker proteins (caspase-3 and PARP) in H1299 and H1975 cells, activated the transcription of IRE1?, increased the expression of GRP78 and XBP-1s, and finally induced apoptosis of H1299 cells. In vivo studies showed that 15 at a dose of 20 mg/kg suppressed tumor growth of S180 cell xenografts in icr mice significantly. Further molecular docking studies suggested that compound 15 could bind well with the ATPase domain of Topoisomerase-II. These data suggest that compound 15 is a promising agent for cancer therapy deserving further research.

| S-EPMC6596340 | biostudies-literature

Design, synthesis and biological evaluation of tryptamine salicylic acid derivatives as potential antitumor agents.

Project description:A series of tryptamine salicylic acid derivatives were synthesized and their antiproliferative activity against MGC-803, MCF-7, HepG2, A549 and HeLa cell lines was evaluated. The structure-activity relationship (SAR) study revealed that different substitutions of the C5 and C3'-C5' positions have certain effects on the anti-proliferation activity. The growth assay revealed that N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide (E20) showed the most potent and broad-spectrum anticancer inhibition of all the cell lines evaluated, and was only more potent than 5-Fu for the gastric cancer cell line. Preliminary studies indicated that compound E20 could inhibit colony formation and migration of MGC-803 cells. The flow cytometry (FCM) results showed that compound E20 arrested the cell cycle in the G2/M phase and induced apoptosis of MGC-803 cells in a concentration-dependent manner. In addition, the western blot results showed that E20 can down-regulate the expression of hexokinase 2. Our studies suggest that the framework of N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide may be consider as a new type of chemical for designing effective anti-cancer drugs targeting gastric cancer cells.

| S-EPMC6482410 | biostudies-literature

Design, synthesis and biological evaluation of C6-modified celastrol derivatives as potential antitumor agents.

Project description:New six C6-celastrol derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activities against nine human cancer cell lines (BGC-823, H4, Bel7402, H522, Colo 205, HepG2 and MDA-MB-468). The results showed that most of the compounds displayed potent inhibition against BGC823, H4, and Bel7402, with IC50s of 1.84-0.39 μM. The best compound NST001A was tested in an in vivo antitumor assay on nude mice bearing Colo 205 xenografts, and showed significant inhibition of tumor growth at low concentrations. Therefore, celastrol C-6 derivatives are potential drug candidates for treating cancer.

| S-EPMC6271447 | biostudies-literature

Synthesis and Biological Evaluation of Phaeosphaeride A Derivatives as Antitumor Agents.

Project description:New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor activity studies were carried out on the HCT-116, PC3, MCF-7, A549, ?562, NCI-?929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All of the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 was potent against six cancer cell lines, HCT-116, PC-3, K562, NCI-H929, Jurkat, and RPMI8226, showing a 47, 13.5, 16, 4, 1.5, and 7-fold increase in anticancer activity comparative to those of etoposide, respectively. Compound 1 possessed selectivity toward the NCI-H929 cell line (IC50 = 1.35 ± 0.69 ?M), while product 7 was selective against three cancer cell lines, HCT-116, MCF-7, and NCI-H929, each having IC50 values of 1.65 ?M, 1.80 ?M and 2.00 ?M, respectively.

| S-EPMC6278656 | biostudies-literature

Synthesis and Biological Evaluation of Novel 4-(4-Formamidophenylamino)-N-methylpicolinamide Derivatives as Potential Antitumor Agents.

Project description:A novel series of 4-(4-formamidophenylamino)-N-methylpicolinamide derivatives were synthesized and evaluated against different tumor cell lines. Experiments in vitro showed that these derivatives could inhibit the proliferation of two kinds of human cancer cell lines (HepG2, HCT116) at low micromolar concentrations and the most potent analog 5q possessed broad-spectrum antiproliferative activity. Experiments in vivo demonstrated that 5q could effectively prolong the longevity of colon carcinoma-burdened mice and slow down the progression of cancer cells by suppression of angiogenesis and the induction of apoptosis and necrosis.

| S-EPMC7926825 | biostudies-literature

Synthesis and evaluation of new sterol derivatives as potential antitumor agents.

Project description:The current optimization of tetrazanbigen (TNBG) on the C-ring provided a series of new sterol derivatives 2a-2n. All new synthesized compounds were screened for their anti-proliferation activities against five human cancer cell lines (HepG2, QGY-7701, SMMC-7721, A-431 and NCI-H23 cell lines) in vitro. Among them, 2a, 2b, 2c, 2m and 2n exhibited high anti-proliferation activities on SMMC-7721, and their IC50 values approach that of the positive control drug cisplatin. Compound 2a not only showed strong anti-proliferation activities against QGY-7701 and HepG2 cell lines, with IC50 values (IC50: 6.81 ± 0.24 μM, 7.69 ± 0.87 μM) better than that of cisplatin (IC50: 8.75 μM, 18.89 ± 2.01 μM), but also exhibited good aqueous solubility (0.15-15 mg mL-1 at pH 7.4 and 2.0). On the most sensitive QGY-7701 cell line, Oil red O staining and western blot analysis were performed. The results suggested that 2a can inhibit the growth of cancer cells possibly by interfering with the lipid metabolism balance of tumor cells, resulting in lipid accumulation and cell apoptosis (lipotoxicity). Moreover, after being treated with 2a, lipid accumulation of QGY-7701 cell was increased in a time and dose dependent manner. Based on these promising results, 2a was selected for drug formulation and further pre-clinical development.

| S-EPMC9083030 | biostudies-literature

Design, Synthesis and Biological Evaluation of Novel 4-Substituted Coumarin Derivatives as Antitumor Agents.

Project description:Herein, fifteen new compounds containing coumarin, 1,2,3-triazole and benzoyl- substituted arylamine moieties were designed, synthesized and tested in vitro for their anticancer activity. The results showed that all tested compounds had moderate antiproliferative activity against MDA-MB-231, a human breast cancer cell line, under both normoxic and hypoxic conditions. Furthermore, the 4-substituted coumarin linked with benzoyl 3,4-dimethoxyaniline through 1,2,3-triazole (compound 5e) displayed the most prominent antiproliferative activities with an IC50 value of 0.03 μM, about 5000 times stronger than 4-hydroxycoumarin (IC50 > 100 μM) and 20 times stronger than doxorubicin (IC50 = 0.60 μM). Meanwhile, almost all compounds revealed general enhancement of proliferation-inhibiting activity under hypoxia, contrasted with normoxia. A docking analysis showed that compound 5e had potential to inhibit carbonic anhydrase IX (CA IX).

| S-EPMC6225359 | biostudies-literature

Lead Optimization: Synthesis and Biological Evaluation of PBT-1 Derivatives as Novel Antitumor Agents.

Project description:Phenanthrene-based tylophorine-1 (PBT-1) was identified previously as a lead compound in an anticancer drug discovery effort based on natural Tylophora alkaloids. An expanded structural optimization using a new more efficient synthetic route provided 14 PBT-derivatives. Eleven compounds displayed obvious antiproliferative activities in cellular assays (GI50 0.55-9.32 μM). The most potent compounds 9c, 9g, and 9h (GI50 < 1 μM) contained a 7-hydroxy group on the phenanthrene B-ring in addition to a pendant piperidine E-ring with different 4-substituents. Compound 9h with NH2 as the piperidine substituent was at least 4-fold more potent against triple-negative breast cancer MDA-MB-231 than estrogen-responsible breast cancer MCF-7 cell growth. In further biological evaluations, the new active compounds induced cell cycle accumulation in the late S and G2/M phase without interfering with microtubule formation or cell morphology. These results on the optimization of the B- and E-rings of PBT-1 should benefit further development of novel antitumor agents.

| S-EPMC8667301 | biostudies-literature

Synthesis, Biological Evaluation and Docking Analysis of Some Novel Quinazolin Derivatives as Antitumor Agents.

Project description:Different acid chlorides (2a-d) reacted with anthranilic acid to produce 2-substituted-3, 1-benzoxazin-4-one (3a-d) which was used as starting material to synthesize some condensed and non-condensed heterocyclic compounds by reaction with nitrogen nucleophiles e.g., hydrazine hydrate, and formamide. Some of the newly synthesized analogues were chosen to evaluate their cytotoxic activity against human carcinoma cell lines (HePG2- MCF7- A549). The docking and the cytotoxic activity results revealed that nearly all of the compounds containing N-phenyl aniline showed signiﬁcant inhibition for the three cell lines.

| S-EPMC4986116 | 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