Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Novel dermacozine-1-carboxamides as promising anticancer agents with tubulin polymerization inhibitory activity.

ABSTRACT: In the present study, novel dermacozine-1-carboxamides (8a-8n) were synthesized and screened for their in vitro cytotoxic activity against three different cancer cell lines: MCF-7 (breast cancer), A-549 (lung cancer) and DU145 (prostate cancer). All the compounds showed more efficiency against the DU145 cell line than against the MCF-7 and A-549 cell lines. Furthermore, 8a (CTC₅₀: 7.02 μM) and 8l (CTC₅₀: 6.32 μM) have been found to be more effective against the DU145 cells as they arrest the cell cycle at the G2/M phase by interfering with tubulin polymerization; these results indicate that these compounds act as potential anti-cancer agents by inhibiting tubulin polymerization.

SUBMITTER: Ghanta VR

PROVIDER: S-EPMC9064817 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Novel dermacozine-1-carboxamides as promising anticancer agents with tubulin polymerization inhibitory activity.

Ghanta Venkata Rao VR Madala Nagaraju N Pasula Aparna A Pindiprolu Sai Kiran S S SKSS Battula Kumara Swamy KS Krishnamurthy Praveen T PT Raman Balamurali B

RSC advances 20190613 32

In the present study, novel dermacozine-1-carboxamides (8a-8n) were synthesized and screened for their in vitro cytotoxic activity against three different cancer cell lines: MCF-7 (breast cancer), A-549 (lung cancer) and DU145 (prostate cancer). All the compounds showed more efficiency against the DU145 cell line than against the MCF-7 and A-549 cell lines. Furthermore, 8a (CTC50: 7.02 μM) and 8l (CTC50: 6.32 μM) have been found to be more effective against the DU145 ...[more]

PMID: 35515253

Similar Datasets

Discovery of Novel 4-Arylisochromenes as Anticancer Agents Inhibiting Tubulin Polymerization.

Project description:XJP-L (8), a derivative of the natural product (±)-7,8-dihydroxy-3-methylisochroman-4-one isolated from the peel of Musa sapien tum L., was found to exhibit weak inhibitory activity of tubulin polymerization (IC50 = 10.6 μM) in our previous studies. Thus, a series of 4-arylisochromene derivatives were prepared by incorporating the trimethoxyphenyl moiety into 8, among which compound (±)-19b was identified as the most potent compound with IC50 values ranging from 10 to 25 nM against a panel of cancer cell lines. Further mechanism studies demonstrated that (±)-19b disrupted the intracellular microtubule network, caused G2/M phase arrest, induced cell apoptosis, and depolarized mitochondria of K562 cells. Moreover, (±)-19b exhibited potent in vitro antivascular and in vivo antitumor activities. Notably, the R-configured enantiomer of (±)-19b, which was prepared by chiral separation, was slightly more potent than (±)-19b and was much more potent than the S-configured enantiomer in both antiproliferative and antitubulin assays. Our findings suggest that (±)-19b deserves further research as a potential antitubulin agent for the treatment of cancers.

| S-EPMC6187416 | biostudies-literature

Novel 8-Methoxycoumarin-3-Carboxamides with potent anticancer activity against liver cancer via targeting caspase-3/7 and β-tubulin polymerization.

Project description:In the present study, we explored the potential of coumarin-based compounds, known for their potent anticancer properties, by designing and synthesizing a novel category of 8-methoxycoumarin-3-carboxamides. Our aim was to investigate their antiproliferative activity against liver cancer cells. Toward this, we developed a versatile synthetic approach to produce a series of 8-methoxycoumarin-3-carboxamide analogues with meticulous structural features. Assessment of their antiproliferative activity demonstrated their significant inhibitory effects on the growth of HepG2 cells, a widely studied liver cancer cell line. Among screened compounds, compound 5 exhibited the most potent antiproliferative activity among the screened compounds (IC50 = 0.9 µM), outperforming the anticancer drug staurosporine (IC50 = 8.4 µM), while showing minimal impact on normal cells. The flow cytometric analysis revealed that compound 5 induces cell cycle arrest during the G1/S phase and triggers apoptosis in HepG2 cells by increasing the percentage of cells arrested in the G2/M and pre-G1 phases. Annexin V-FITC/PI screening further supported the induction of apoptosis without significant necrosis. Further, compound 5 exhibited the ability to activate caspase3/7 protein and substantially inhibited β-tubulin polymerization activity in HepG2 cells. Finally, molecular modelling analysis further affirmed the high binding affinity of compound 5 toward the active cavity of β-tubulin protein, suggesting its mechanistic involvement. Collectively, our findings highlight the therapeutic potential of the presented class of coumarin analogues, especially compound 5, as promising candidates for the development of effective anti-hepatocellular carcinoma agents.

| S-EPMC10693084 | biostudies-literature

New pyrrole derivatives with potent tubulin polymerization inhibiting activity as anticancer agents including hedgehog-dependent cancer.

Project description:We synthesized 3-aroyl-1-arylpyrrole (ARAP) derivatives as potential anticancer agents having different substituents at the pendant 1-phenyl ring. Both the 1-phenyl ring and 3-(3,4,5-trimethoxyphenyl)carbonyl moieties were mandatory to achieve potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARAP 22 showed strong inhibition of the P-glycoprotein-overexpressing NCI-ADR-RES and Messa/Dx5MDR cell lines. Compounds 22 and 27 suppressed in vitro the Hedgehog signaling pathway, strongly reducing luciferase activity in SAG treated NIH3T3 Shh-Light II cells, and inhibited the growth of medulloblastoma D283 cells at nanomolar concentrations. ARAPs 22 and 27 represent a new potent class of tubulin polymerization and cancer cell growth inhibitors with the potential to inhibit the Hedgehog signaling pathway.

| S-EPMC4154712 | biostudies-literature

Design, synthesis, and biological evaluation of novel 5,6,7-trimethoxy quinolines as potential anticancer agents and tubulin polymerization inhibitors.

Project description:ObjectivesMicrotubules have key roles in essential cellular processes such as mitosis, cell motion, and intracellular organelle transport. Increasing interest has been given to tubulin binding compounds after the introduction of taxanes into clinical oncology. The object of this study was synthesis and biological evaluation of novel 5,6,7-trimethoxy quinolines as tubulin inhibitors.Materials and methodsThe cytotoxicity of the newly synthesized compounds was assessed against different human cancer cell lines including MCF-7, A2780, MCF-7/MX, A2780/RCIS, and normal cells. Compounds demonstrating the most antiproliferative activity, were chosen to examine their tubulin inhibition activity and their ability to arrest the cell cycle and induce apoptosis. Molecular docking studies and molecular dynamics simulation of compound 7e in the catalytic site of tubulin were performed.ResultsMost of the synthesized quinolines showed moderate to signiﬁcant cytotoxic activity against human cancer cells. Compounds 7e and 7f, possessing N-(4-benzoyl phenyl) and N-(4-phenoxy phenyl), respectively, exhibited the most antiproliferative activity more potent than the other compounds and exhibited similar antiproliferative activity on both resistant and parental cancer cells.ConclusionFlow cytometry analysis of A2780, A2780/RCIS, MCF-7, and MCF-7/MX cancer cells treated with 7e and 7f exhibited that these compounds arrested the cell cycle (at the G2/M phase) and induced cellular apoptosis in A2780 cancer cells. These quinolines inhibited tubulin polymerization in a way resembling that of CA-4. Molecular dynamics simulation and molecular docking studies of compound 7e into the binding site of tubulin displayed the probable interactions of 7e with the binding site of tubulin.

| S-EPMC7811808 | biostudies-literature

Design and synthesis of novel 5-(4-chlorophenyl)furan derivatives with inhibitory activity on tubulin polymerization.

Project description:AimDiscovery of novel series of colchicine binding site inhibitors (CBSIs).Materials & methodsIsoxazoline 3a-d, pyrazoline 4a-b, 7a-f and 8a-f, cyclohexenone 9a-b and 10a-b or pyridine derivatives 11a-b were synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity. Most of the compounds displayed potent to moderate antitumor activity against leukemia SR cell line.7c, 7e and 11a were more potent than colchicine with IC50 of 0.09, 0.05 and 0.06 μM, and percentage inhibition in tubulin polymerization of 95.2, 96.0 and 96.3%, respectively. Compounds 7c and 11a showed cell-cycle arrest at G2/M phase and induced apoptosis and were able to bind the colchicine binding site of tubulin with comparable affinity to colchicine. Docking study showed that these compounds may interact with tubulin exploiting a binding cavity not commonly reported in the binding of CBSI.ConclusionCompounds 7c and 11a may be considered as promising CBSI based on their excellent activity and favorable drug likeness profile.

| S-EPMC6479276 | biostudies-literature

Design, Synthesis, Cytotoxic Evaluation and Molecular Docking of New Fluoroquinazolinones as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects.

Project description:A series of new fluoroquinazolinone 6⁻8 and 10a⁻g derivatives was designed, prepared and screened for their in vitro cytotoxic activity against human cancer cell lines MCF-7 and MDA-MBA-231. Compounds 6 (IC50 = 0.35 ± 0.01 µM), 10f (IC50 = 0.71 ± 0.01 µM), 10d (IC50 = 0.89 ± 0.02 µM) and 10a (IC50 = 0.95 ± 0.01 µM) displayed broad spectrum anticancer activity better than the reference drug gefitinib (IC50 = 0.97 ± 0.02 µM) against MCF-7. Compounds 10e (IC50 = 0.28 ± 0.02 µM), 10d (IC50 = 0.38 ± 0.01 µM), 7 (IC50 = 0.94 ± 0.07 µM) and 10c (IC50 = 1.09 ± 0.01 µM) showed better activity than the reference gefitinib (IC50 = 1.30 ± 0.04 µM) against MDA-MBA-231. Moreover, EGFR and tubulin inhibition assays were performed for the highest active derivatives and showed remarkable results comparing to the reference drugs. In order to assess and explain their binding affinities, molecular docking simulation was studied against EGFR and tubulin binding sites. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated.

| S-EPMC6032053 | biostudies-literature

Design, Synthesis and Cytotoxic Evaluation of Novel Chalcone Derivatives Bearing Triazolo[4,3-a]-quinoxaline Moieties as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects.

Project description:A series of hybrid of triazoloquinoxaline-chalcone derivatives 7a-k were designed, synthesized, fully characterized, and evaluated for their cytotoxic activity against three target cell lines: human breast adenocarcinoma (MCF-7), human colon carcinoma (HCT-116), and human hepatocellular carcinoma (HEPG-2). The preliminary results showed that some of these chalcones like 7b-c, and 7e-g exhibited significant antiproliferative effects against most of the cell lines, with selective or non-selective behavior, indicated by IC50 values in the 1.65 to 34.28 µM range. In order to investigate the mechanistic aspects of these active compounds, EGFR TK and tubulin inhibitory activities were measured as further biological assays. The EGFR TK assay results revealed that the derivatives 7a-c, 7e, and 7g could inhibit the EGFR TK in the submicromolar range (0.093 to 0.661 µM). Moreover, an antitubulin polymerization effect was noted for the active derivatives compared to the reference drug colchicine, with compounds 7e and 7g displaying 14.7 and 8.4 micromolar activity, respectively. Furthermore, a molecular docking study was carried out to explain the observed effects and the binding modes of these chalcones with the EGFR TK and tubulin targets.

| S-EPMC5943945 | biostudies-literature

The Design and Development of Potent Small Molecules as Anticancer Agents Targeting EGFR TK and Tubulin Polymerization.

Project description:Some novel anthranilate diamides derivatives 4a-e, 6a-c and 9a-d were designed and synthesized to be evaluated for their in vitro anticancer activity. Structures of all newly synthesized compounds were confirmed by infra-red (IR), high-resolution mass (HR-MS) spectra, ¹H nuclear magnetic resonance (NMR) and 13C nuclear magnetic resonance (NMR) analyses. Cytotoxic screening was performed according to (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium (MTT) assay method using erlotinib as a reference drug against two different types of breast cancer cells. The molecular docking study was performed for representative compounds against two targets, epidermal growth factor receptor (EGFR) and tubulin in colchicine binding site to assess their binding affinities in order to rationalize their anticancer activity in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticancer activity for these newly synthesized compounds. Biological data for most of the anthranilate diamide showed excellent activity with nanomolar or sub nanomolar half maximal inhibitory concentration (IC50) values against tumor cells. EGFR tyrosine kinase (TK) inhibition assay, tubulin inhibition assay and apoptosis analysis were performed for selected compounds to get more details about their mechanism of action. Extensive structure activity relationship (SAR) analyses were also carried out.

| S-EPMC5855630 | biostudies-literature

Tubulin-interactive natural products as anticancer agents.

Project description:This review provides an overview of the discovery, structures, and biological activities of anticancer natural products that act by inhibiting or promoting the assembly of tubulin to microtubules. The emphasis is on providing recent information on those compounds in clinical use or in advanced clinical trials. The vinca alkaloids, the combretastatins, NPI-2358, the halichondrin B analogue eribulin, dolastatin 10, noscapine, hemiasterlin, and rhizoxin are discussed as tubulin polymerization inhibitors, while the taxanes and the epothilones are the major classes of tubulin polymerization promoters presented, with brief treatments of discodermolide, eleutherobin, and laulimalide. The challenges and future directions of tubulin-interactive natural products-based drug discovery programs are also discussed briefly.

| S-EPMC2765517 | biostudies-other

Anticancer activity of a novel small molecule tubulin inhibitor STK899704.

Project description:We have identified the small molecule STK899704 as a structurally novel tubulin inhibitor. STK899704 suppressed the proliferation of cancer cell lines from various origins with IC50 values ranging from 0.2 to 1.0 μM. STK899704 prevented the polymerization of purified tubulin in vitro and also depolymerized microtubule in cultured cells leading to mitotic arrest, associated with increased Cdc25C phosphorylation and the accumulation of both cyclin B1 and polo-like kinase 1 (Plk1), and apoptosis. Unlike many anticancer drugs such as Taxol and doxorubicin, STK899704 effectively displayed antiproliferative activity against multidrug-resistant cancer cell lines. The proposed binding mode of STK899704 is at the interface between αβ-tubulin heterodimer overlapping with the colchicine-binding site. Our in vivo carcinogenesis model further showed that STK 899704 is potent in both the prevention and regression of tumors, remarkably reducing the number and volume of skin tumor by STK899704 treatment. Moreover, it was significant to note that the efficacy of STK899704 was surprisingly comparable to 5-fluorouracil, a widely used anticancer therapeutic. Thus, our results demonstrate the potential of STK899704 to be developed as an anticancer chemotherapeutic and an alternative candidate for existing therapies.

| S-EPMC5351965 | 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