Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and Evaluation of Estradiol Derivatives as Anti-Breast Cancer Agents.

ABSTRACT: 3-N-alkyloxyestradiol derivatives were synthesized, characterized and tested for activity in MCF-7 human breast cancer cells. Among the compounds, the diisopropyl and piperidinyl derivatives were found to be more active than 4-hydroxytamoxifen (HO-Tam), the active metabolite of tamoxifen based upon IC(50) values. The IC(50)s were correlated with structures using molecular modeling.

SUBMITTER: Cooperwood JS

PROVIDER: S-EPMC2882686 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and Evaluation of Estradiol Derivatives as Anti-Breast Cancer Agents.

Cooperwood John S JS Edwards Jesse J Musa Musiliyu M Simmons Devora D Mian Abdul D AD Park Kwon-Kyun KK Wan Zhongliang Z

Letters in drug design & discovery 20100701 6

3-N-alkyloxyestradiol derivatives were synthesized, characterized and tested for activity in MCF-7 human breast cancer cells. Among the compounds, the diisopropyl and piperidinyl derivatives were found to be more active than 4-hydroxytamoxifen (HO-Tam), the active metabolite of tamoxifen based upon IC(50) values. The IC(50)s were correlated with structures using molecular modeling. ...[more]

PMID: 20543998

Similar Datasets

Design, synthesis, and evaluation of estradiol-linked genotoxicants as anti-cancer agents.

Project description:A series of bifunctional compounds was prepared consisting of 17beta estradiol linked to a DNA damaging N,N-bis-(2-chloroethyl)aniline. The objective of our studies was to determine the characteristics of the linker that permitted both reaction with DNA and binding of the resultant covalent adducts to the estrogen receptor. Linker characteristics were pivotal determinants underlying the ability of the compounds to kill selectively breast cancer cells that express the estrogen receptor.

| S-EPMC4096836 | biostudies-literature

Design, synthesis and biological evaluation of new carbazole derivatives as anti-cancer and anti-migratory agents.

Project description:Based on the efficacy of EHop-016 as an inhibitor of migration and Rac1 activation, a new series of carbazole derivatives has been synthesized. Cytotoxic and anti-migratory effects of these compounds were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. Preliminary investigations of their anticancer activity demonstrated that several compounds have moderate antiproliferative effects on cancer cell lines with GI50 values in the range of 13-50?µM. Furthermore, compounds 3b and 11b inhibit migration activity of metastatic cell line MDA-MB-231 by 32% and 34%, respectively. Compound 11b was shown to inhibit activation of the Rho GTPase Rac1 by 55% at 250?nM in both MDA-MB-231 and MDA-MB-435 cell lines. Compared with the IC50 of Rac1 inhibition by lead compound EHop-016 of 1.1?µM, compound 11b demonstrates 4X improved in vitro efficacy.

| S-EPMC5822041 | biostudies-literature

Design, Synthesis and Preliminary Biological Evaluation of Benzylsulfone Coumarin Derivatives as Anti-Cancer Agents.

Project description:In this work, a series of benzylsulfone coumarin derivatives 5a-5o were synthesized and characterized. Kinase inhibitory activity assay indicated that most of the compounds showed considerable activity against PI3K. Anti-tumor activity studies of the active compounds were also carried out in vitro on the Hela, HepG2, H1299, HCT-116, and MCF-7 tumor cell lines by MTS assay. The structure-activity relationships (SARs) of these compounds were analyzed in detail. Compound 5h exhibited the most potent activities against the mentioned cell lines with IC50 values ranging from 18.12 to 32.60 μM, followed by 5m with IC50 values of 29.30-42.14 μM. Furthermore, 5h and 5m clearly retarded the migration of Hela cells in vitro. Next, an in silico molecular docking study was conducted to evaluate the binding models of 5h and 5m towards PI3Kα and PI3Kβ. Collectively, the above findings suggested that compounds 5h and 5m might be promising PI3K inhibitors deserving further investigation for cancer treatment.

| S-EPMC6891324 | biostudies-literature

Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents.

Project description:Colorectal cancer (CRC) is a common malignant tumour of human digestive tract. The high mortality rate of CRC is closely related to the limitations of existing treatments. Thus, there is an urgent need to search for new anti-CRC agents. In this work, twenty novel coumarin-dithiocarbamate derivatives (IDs) were designed, synthesized and evaluated in vitro. The results suggest that the most active compound ID-11 effectively inhibited the proliferation of CRC cell lines while shown little impact on normal colon epithelial cells. Mechanism studies revealed that ID-11 displayed bromodomain-containing protein 4 inhibitory activity, and induced G2/M phase arrest, apoptosis as well as decreased the expression levels of the key genes such as c-Myc and Bcl-2 in CRC cell lines. Moreover, the ADMET properties prediction results shown that ID-11 possess well metabolic characteristics without obvious toxicities. Our data demonstrated that compound ID-11 may be a promising anti-CRC agent and deserved for further development.

| S-EPMC8759731 | biostudies-literature

Synthesis and Biological Evaluation of Thalidomide Derivatives as Potential Anti-Psoriasis Agents.

Project description:Several thalidomide derivatives were synthesized and evaluated for their anti-inflammatory activity. Introduction of the benzyl group to the parent thalidomide is unfavorable in which 2-(1-benzyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (4a) was inactivated. However, the inhibitory activities on TNF-? and IL-6 expression in HaCaT cells were improved by the substitution of a chloro- or methoxy- group at the phenyl position of 4a. The IL-6 inhibitory activity decreased in an order of 5c (69.44%) > 4c (48.73%) > 6c (3.19%) indicating the 3-substituted derivative is more active than the 4-substituted counterpart, which in turn is more active than the 2-substituted counterpart. Among them, 2-[1-(3-chlorobenzyl)-2,6-dioxopiperidin-3-yl]isoindoline-1,3-dione (5c) was found to inhibit TNF-? and IL-6 expression in HaCaT cells with a higher potency than thalidomide and no significant cell cytotoxicity was detected at 10 ?M. In psoriasis, Compound 5c reduced IL-6, IL-8, IL-1? and IL-24 in imiquimod-stimulated models. Our results indicated that compound 5c is a potential lead of novel anti-psoriasis agents. Structural optimization of compound 5c and its in vivo assay are ongoing.

| S-EPMC6212999 | biostudies-literature

Synthesis and biological evaluation of new ligustrazine derivatives as anti-tumor agents.

Project description:To discover new anti-cancer agents with multi-effect and low toxicity, a series of ligustrazine derivatives were synthesized using several effective anti-tumor ingredients of Shiquandabu Wan as starting materials. Our idea was enlightened by the "combination principle" in drug discovery. The ligustrazine derivatives' anti-tumor activities were evaluated on the HCT-8, Bel-7402, BGC-823, A-549 and A2780 human cancer cell lines. In addition the angiogenesis activities were valued by the chick chorioallantoic membrane (CAM) assay. 1,7-bis(4-(3,5,6-Trimethylpyrazin-2-yl)-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (4) and 3 ?,12 ?-dihydroxy-5?-dholanic acid-3,5,6-trimethylpyrazin-2-methyl ester (5) not only displayed antiproliferative activities on these cancer cells, but also dramatically suppressed normal angiogenesis in CAM. The LD?? value of the compound 5 exceeded 3.0 g/kg by oral administration in mice.

| S-EPMC6268357 | biostudies-literature

Synthesis and biological evaluation of new 3-amino-2-azetidinone derivatives as anti-colorectal cancer agents.

Project description:Several synthetic combretastatin A4 (CA-4) derivatives were recently prepared to increase the drug efficacy and stability of the natural product isolated from the South African tree Combretum caffrum. A group of ten 3-amino-2-azetidinone derivatives, as combretastatin A4 analogues, was selected through docking experiments, synthesized and tested for their anti-proliferative activity against the colon cancer SW48 cell line. These molecules, through the formation of amide bonds in position 3, allow the synthesis of various derivatives that can modulate the activity with great resistance to hydrolytic conditions. The cyclization to obtain the 3-aminoazetidinone ring is highly diastereoselective and provides a trans biologically active isomer under mild reaction conditions with better yields than the 3-hydroxy-2-azetidinone synthesis. All compounds showed IC50 values ranging between 14.0 and 564.2 nM, and the most active compound showed inhibitory activity against tubulin polymerization in vitro, being a potential therapeutic agent against colon cancer.

| S-EPMC6071799 | biostudies-literature

The synthesis and biological evaluation of sanguinarine derivatives as anti-non-small cell lung cancer agents.

Project description:A novel series of sanguinarine (SA) derivatives were synthesized and evaluated as anti-non-small cell lung cancer (NSCLC) agents. The compounds inhibited A549 and H1975 NSCLC cells with IC50 values of 0.96 - >30 μM and 0.79 - >30 μM, respectively. Compounds 8d-8j exhibited low micromolar inhibitory activity and indicated that the C6-position of SA was tolerated to be substituted by hydrophilic groups and CN. Further investigation of their mechanism of action showed that compound 8h induced apoptosis of A549 and H1975 cells by inhibiting the Akt signaling pathway and elevating the reactive oxygen species (ROS). This study provided a strategy for developing new anti-cancer agents.

| S-EPMC7489057 | biostudies-literature

Design, synthesis and biological evaluation of 2-quinolyl-1,3-tropolone derivatives as new anti-cancer agents.

Project description:Tropolones are promising organic compounds that can have important biologic effects. We developed a series of new 2-quinolyl-1,3-tropolones derivatives that were prepared by the acid-catalyzed reaction of 4,7-dichloro-2-methylquinolines with 1,2-benzoquinones. 2-Quinolyl-1,3-tropolones have been synthesized and tested for their anti-proliferative activity against several human cancer cell lines. Two compounds (3d and mixture B of 3i-k) showed excellent activity against six cancer cell lines of different tissue of origin. The promising compounds 3d and mixture B of 3i-k also demonstrated induction of apoptotic cell death of ovarian cancer (OVCAR-3, OVCAR-8) and colon cancer (HCT 116) cell lines and affected ERK signaling. In summary, 2-quinolyl-1,3-tropolones are promising compounds for development of effective anticancer agents.

| S-EPMC8121267 | biostudies-literature

Design and Synthesis of Tetrahydroisoquinoline Derivatives as Anti-Angiogenesis and Anti-Cancer Agents.

Project description:AimThe aim of our research work is the synthesis of tetrahydroisoquinoline derivatives as anti-Angiogenesis and anti-cancer agents.BackgroundCancer is the second leading cause of deaths in the United States. The current recovery rate from the advanced treatment for the cancer is excessively low. Therefore, the identification of novel, potent, and less toxic anticancer agents remains a top priority.ObjectiveTo evaluate anti-angiogenesis and anticancer activities of THIQs on different colorectal cancer cell lines (CRC) viz., Colo320, DLD-1, HCT116, SNU-C1, SW480, and GSK3b in pre-treated viability HCT116. and to carry out molecular docking studies of THIQs.MethodsTwenty synthesized THIQs were screened in the Eli Lilly's Open Innovation Drug Discovery Program and selected twelve compounds for in vitro primary screening in the KRas (Kirsten rat sarcoma)-Wnt SL (Synthetic Lethal) in the basal viability of different colon cancer cell lines. Docking studies of the active THIQs were also performed in our laboratory, targeting the active sites of KRas and VEGF receptors.ResultsCompound GM-3-18 was found to possess significant activities for KRas inhibition, with IC50 values in the range of 0.9 μM to 10.7 μM, for all colon cancer cell lines. Compound GM-3-121 showed potent anti-angiogenesis activity with IC50 = 1.72 μM. Molecular docking studies showed that the carbonyl oxygen atoms of GM-3-18 and GM-3-121 showed hydrogen bonding interactions with the hydrogen of - OH groups of THR 74 (A).ConclusionThe results indicated that all the compounds showed moderate to high activity for KRas inhibition. The THIQs bearing the chloro group at the 4-position of the phenyl ring (GM-3-18) exhibited significant KRas inhibition against all colon cancer cell lines.

| S-EPMC8694809 | 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