Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Biological evaluation of tubulysin A: a potential anticancer and antiangiogenic natural product.

ABSTRACT: Tubulysin A (tubA) is a natural product isolated from a strain of myxobacteria that has been shown to depolymerize microtubules and induce mitotic arrest. The potential of tubA as an anticancer and antiangiogenic agent is explored in the present study. tubA shows potent antiproliferative activity in a panel of human cancer cell lines irrespective of their multidrug resistance properties. It induces apoptosis in cancer cells but not in normal cells and shows significant potential antiangiogenic properties in several in vitro assays. It is efficacious in initial animal studies using a hollow fibre assay with 12 different human tumour cell lines. This study suggests that both in vitro and preclinical profiles of tubA may translate into clinically useful anticancer properties.

SUBMITTER: Kaur G

PROVIDER: S-EPMC1462728 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Biological evaluation of tubulysin A: a potential anticancer and antiangiogenic natural product.

Kaur Gurmeet G Hollingshead Melinda M Holbeck Susan S Schauer-Vukasinović Vesna V Camalier Richard F RF Dömling Alexander A Agarwal Seema S

The Biochemical journal 20060601 2

Tubulysin A (tubA) is a natural product isolated from a strain of myxobacteria that has been shown to depolymerize microtubules and induce mitotic arrest. The potential of tubA as an anticancer and antiangiogenic agent is explored in the present study. tubA shows potent antiproliferative activity in a panel of human cancer cell lines irrespective of their multidrug resistance properties. It induces apoptosis in cancer cells but not in normal cells and shows significant potential antiangiogenic p ...[more]

PMID: 16489930

Similar Datasets

Total synthesis and biological evaluation of tubulysin U, tubulysin V, and their analogues.

Project description:A stereoselective total synthesis of the cytotoxic natural products tubulysin U, tubulysin V, and its unnatural epimer epi-tubulysin V, is reported. Simplified analogues containing N,N-dimethyl-D-alanine as a replacement for the N-terminal N-Me-pipecolinic acid residue of the tubulysins are also disclosed. Biological evaluation of these natural products and analogues provided key information with regard to structural and stereochemical requirements for antiproliferative activity and tubulin polymerization inhibition.

| S-EPMC4183140 | biostudies-literature

Discovery of Novel Antiangiogenic Marine Natural Product Scaffolds.

Project description:Marine natural products (MNPs) are recognized for their structural complexity, diversity, and novelty. The vast majority of MNPs are pharmacologically relevant through their ability to modulate macromolecular targets underlying human diseases. Angiogenesis is a fundamental process in cancer progression and metastasis. Targeting angiogenesis through selective modulation of linked protein kinases is a valid strategy to discover novel effective tumor growth and metastasis inhibitors. An in-house marine natural products mini-library, which comprises diverse MNP entities, was submitted to the Lilly's Open Innovation Drug Discovery platform. Accepted structures were subjected to in vitro screening to discover mechanistically novel angiogenesis inhibitors. Active hits were subjected to additional angiogenesis-targeted kinase profiling. Some natural and semisynthetic MNPs, including multiple members of the macrolide latrunculins, the macrocyclic oxaquinolizidine alkaloid araguspongine C, and the sesquiterpene quinone puupehenone, showed promising results in primary and secondary angiogenesis screening modules. These hits inhibited vascular endothelial growth factor (VEGF)-mediated endothelial tube-like formation, with minimal cytotoxicity at relevant doses. Secondary kinase profiling identified six target protein kinases, all involved in angiogenesis signaling pathways. Molecular modeling and docking experiments aided the understanding of molecular binding interactions, identification of pharmacophoric epitopes, and deriving structure-activity relationships of active hits. Marine natural products are prolific resources for the discovery of chemically and mechanistically unique selective antiangiogenic scaffolds.

| S-EPMC4820311 | biostudies-literature

Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents.

Project description:Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds 3c and 4a were active against the tested cancer cell lines, being more cytotoxic for the HL-60 cell line with IC50 values of 13.08 ?M and 11.38 ?M, respectively. Regarding the protein kinase inhibition assay, 3c inhibited seven different kinases and 4a strongly inhibited the CK1?/? kinase. The studied kinases are involved in several cellular functions such as proliferation, migration, cell death and cell cycle progression. Additional analysis by flow cytometry revealed that 3c and 4a caused depolarization of the mitochondrial membrane, suggesting apoptosis mediated by the intrinsic pathway. Compound 3c induced arrest in G1 phase of the cell cycle on HL-60 cells, and in the annexin V assay approximately 50% of cells were in apoptosis at the highest concentration tested (26 ?M). Compound 4a inhibited cell cycle by accumulation of abnormal postmitotic cells at G1 phase and induced DNA fragmentation at the highest concentration (22 ?M).

| S-EPMC6958387 | biostudies-literature

Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone?A.

Project description:Natural products have historically been a major source of antibiotics and therefore novel scaffolds are constantly of interest. The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone?A, 15 structural analogues to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

| S-EPMC6033662 | biostudies-literature

Synthesis and Evaluation of Novel Anticancer Compounds Derived from the Natural Product Brevilin A.

Project description:Cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018, and this burden continues to increase. Therefore, there is a clear and urgent need for novel drugs with increased efficacy for the treatment of different cancers. Previous research has demonstrated that brevilin A (BA) exerts anticancer activity in various cancers, including human multiple myeloma, breast cancer, lung cancer, and colon carcinoma, suggesting the anticancer potential present in the chemical scaffold of BA. Here, we designed and synthesized a small library of 12 novel BA derivatives and evaluated the biological anticancer effects of the compounds in various cancer cell lines. The results of this structure-activity relationship study demonstrated that BA derivatives BA-9 and BA-10 possessed significantly improved anticancer activity toward lung, colon, and breast cancer cell lines. BA-9 and BA-10 could more effectively reduce cancer cell viability and induce DNA damage, cell-cycle arrest, and apoptosis when compared with BA. Our findings represent a significant step forward in the development of novel anticancer entities.

| S-EPMC7315608 | biostudies-literature

Pyridine-Ureas as Potential Anticancer Agents: Synthesis and In Vitro Biological Evaluation.

Project description:In our endeavor towards the development of effective anticancer agents, a novel series of pyridine-ureas 8a?n were synthesized. All the newly prepared derivatives were evaluated in vitro for their growth inhibitory activity towards the proliferation of breast cancer MCF-7 cell line. Compounds 8e and 8n were found to be the most active congeners against MCF-7 cells (IC50 = 0.22 and 1.88 µM after 48 h treatment; 0.11 and 0.80 µM after 72 h treatment, respectively) with increased activity compared to the reference drug doxorubicin (IC50 = 1.93 µM). Moreover, eight selected pyridines 8b, 8d, 8e, 8i, 8j and 8l?n were evaluated for their in vitro anticancer activity according to the US-NCI protocol. Pyridines 8b and 8e proved to be the most effective anticancer agents in the NCI assay with mean inhibition = 43 and 49%, respectively. Both 8b and 8e exhibited anti-proliferative activity against all tested cancer cell lines from all subpanels growth inhibition (GI for 8b; 12?78%, GI for 8e; 15?91%). Pyridines 8b and 8e were screened in vitro for their inhibitory activity against VEGFR-2. Both compounds inhibited VEGFR-2 at micromolar IC50 values 5.0 ± 1.91 and 3.93 ± 0.73 µM, respectively. The most active pyridines were filtered according to the Lipinski and Veber rules and all of them passed these filters. Finally, several ADME descriptors were predicted for the active pyridines through a theoretical kinetic study.

| S-EPMC6100082 | biostudies-other

Family-level stereoselective synthesis and biological evaluation of pyrrolomorpholine spiroketal natural product antioxidants.

Project description:The pyranose spiroketal natural products pollenopyrroside A and shensongine A (also known as xylapyrroside A, ent-capparisine B) have been synthesized by stereoselective spirocyclizations of a common C1-functionalized glycal precursor. In conjunction with our previously reported syntheses of the corresponding furanose isomers, this provides a versatile family-level synthesis of the pyrrolomorpholine spiroketal natural products and analogues. In rat mesangial cells, hyperglycemia-induced production of reactive oxygen species, which is implicated in diabetic nephropathy, was inhibited by pollenopyrroside A and shensongine A with mid-?M IC50 values, while unnatural C2-hydroxy analogues exhibited more potent, sub-?M activity.

| S-EPMC5571482 | biostudies-literature

Total synthesis of psoralidin, an anticancer natural product.

Project description:A base-catalyzed condensation of phenyl acetate with acid chloride, followed by intramolecular cyclization and microwave-assisted cross-metathesis reaction, leads to the first total synthesis of psoralidin, a natural product with a broad range of biological activities, in a highly convergent and regioselective manner.

| S-EPMC2662043 | biostudies-literature

Synthesis and Biological Evaluation of Small Molecules as Potential Anticancer Multitarget Agents.

Project description:Twenty-six triazole-based derivatives were designed for targeting both PD-L1 (programmed death receptor ligand 1) and VEGFR-2 (vascular endothelial growth factor receptor 2). These compounds were synthetized and biologically evaluated as multitarget inhibitors of VEGFR-2, PD-L1 and c-Myc proteins. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, A-549, and MCF-7) and on the non-tumor cell line HEK-293 was determined. The effects on the abovementioned biological targets were evaluated for some selected compounds. Compound 23, bearing a p-chlorophenyl group, showed better results than sorafenib in regard to the downregulation of VEGFR-2 and a similar effect to BMS-8 on both PD-L1 and c-Myc proteins. The antiangiogenic and antivascular activities of chloro derivatives were also established by endothelial microtube formation assay on Matrigel®.

| S-EPMC9266368 | biostudies-literature

Total Synthesis of Callyspongiolide: An Anticancer Marine Natural Product.

Project description:The stereoselective total synthesis of cytotoxic marine macrolide callyspongiolide has been reported. The 14-membered macrolactone ring along with Z-olefin in the molecule was constructed via an intramolecular Horner-Wadsworth-Emmons olefination in a Z-selective fashion. The other E-olefinic moiety as well as the C9 stereocenter was introduced via stereoselective addition of the methyl group in an SN2' fashion. The C5 stereocenter was installed via Sakurai allylation, whereas the C7 center was fixed by Jacobsen hydrolytic kinetic resolution. The C12 methyl and C13 hydroxy centers were fixed via Macmillan coupling reaction. The macrolactone core with a vinyl iodide side chain was coupled with the known alkyne fragment to complete the synthesis.

| S-EPMC6643460 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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