Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and Discovery of Estra-1,3,5(10),6,8-pentaene-2,16?-diol.

ABSTRACT: A metallacycle-centered approach to the assembly of partially aromatic synthetic steroids was investigated as a means to prepare a boutique collection of unique steroidal agents. The synthesis and discovery of estra-1,3,5(10),6,8-pentaene-2,16?-diol (VII) is described, along with structure-activity relationships related to its cytotoxic properties. Overall, VII was found to have a GI50 = 0.2 ?g/mL (?800 nM) in MDA-MB-231 human breast cancer cells, be an efficacious estrogen receptor agonist with potency for ER? > ER? (ER? EC50 = 21 nM), possess selective affinity to the cdc-2-like kinase CLK4 (Kd = 350 nM), and be phenotypically related to paclitaxel by an unbiased panel assessment.

SUBMITTER: Wai H

PROVIDER: S-EPMC6415968 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and Discovery of Estra-1,3,5(10),6,8-pentaene-2,16α-diol.

Wai HtooTint H Du Kang K Anesini Jason J Kim Wan Shin WS Eastman Alan A Micalizio Glenn C GC

Organic letters 20180917 19

A metallacycle-centered approach to the assembly of partially aromatic synthetic steroids was investigated as a means to prepare a boutique collection of unique steroidal agents. The synthesis and discovery of estra-1,3,5(10),6,8-pentaene-2,16α-diol (VII) is described, along with structure-activity relationships related to its cytotoxic properties. Overall, VII was found to have a GI<sub>50</sub> = 0.2 μg/mL (∼800 nM) in MDA-MB-231 human breast cancer cells, be an efficacious estrogen receptor a ...[more]

PMID: 30221523

Similar Datasets

3-Iodo-8?,9?,14?-estra-1,3,5(10)-trien-17-one.

Project description:In the title compound, C(18)H(21)IO, the cyclo-hexane ring adopts a chair conformation, whereas the cyclo-pentane ring and the ten-membered tetra-line portions each adopt an envelope conformation. For the five-membered ring, the methine C atom deviates by 0.638?(4)?Å (r.m.s. of the four other atoms is 0.005?Å) and for the ten-membered ring, the methine C atom constituting the flap deviates by 0.671?(3)?Å (r.m.s. of the other nine atoms is 0.066?Å).

| S-EPMC2969661 | biostudies-literature

17-Deoxoestrone [estra-1,3,5(10)-trien-3-ol]-methanol (3/1).

Project description:Three independent mol-ecules of the title estrone derivative and a mol-ecule of methanol comprise the asymmetric unit of the title compound [systematic name: 13-methyl-6,7,8,9,11,12,13,14,15,16-deca-hydro-cyclo-penta-[a]phenanthren-3-ol-meth-an-ol (3/1)], 3C(18)H(24)O·CH(3)OH. Two of the estrone mol-ecules exhibit 50:50 disorder (one displays whole-mol-ecule disorder and the other partial disorder in the fused five- and six-membered rings) so that five (partial) mol-ecular conformations are discernable. The conformation of the six-membered ring abutting the aromatic ring is close to a half-chair in all five components. The conformation of the six-membered ring fused to the five-membered ring is based on a chair with varying degrees of distortion ranging from minor to significant. Two distinct conformations are found for the five-membered ring: in four mol-ecules, the five-membered ring is twisted about the bond linking it to the six-membered ring, and in the other, the five-membered ring is an envelope with the quaternary C atom being the flap atom. The crystal packing features O-H⋯O hydrogen bonding whereby the four mol-ecules comprising the asymmetric unit are linked into a supra-molecular chain along the b axis.

| S-EPMC3089339 | biostudies-literature

17α-Ethynyl-3-methoxy-estra-1,3,5(10),9(11)-tetraen-17-ol.

Project description:In the title compound, C(21)H(24)O(2), rings B, C and D adopt half-chair, distorted half-chair and envelope conformations, respectively. In the crystal structure, there is an inter-molecular O-H⋯O hydrogen bond. The mol-ecules are arranged in a head-to-tail fashion, with the meth-oxy and hydr-oxy groups forming a two-dimensional hydrogen-bond network.

| S-EPMC2961110 | biostudies-literature

Crystal structure of bis-[3-meth-oxy-17?-estra-1,3,5(10)-trien-17-yl] oxalate.

Project description:In the title compound, C40H50O6, a symmetrical steroid oxalate diester, the dihedral angle between the CO2 planes of the oxalate linker is 61.5?(5)° and the C-C bond length is 1.513?(6)?Å. The steroid B, C and D rings adopt half-chair, chair and envelope conformations, respectively, in both halves of the mol-ecule, which adopts an overall shallow V-shaped conformation. In the crystal, mol-ecules are linked by weak C-H?O inter-actions, forming a three-dimensional network.

| S-EPMC4158478 | biostudies-literature

Crystal structure of 16-ferrocenylmethyl-3β-hydroxy-estra-1,3,5(10)-trien-17-one: a potential chemotherapeutic drug.

Project description:A new ferrocene complex, 16-ferrocenylmethyl-3β-hy-droxy-estra-1,3,5(10)-trien-17-one dimethyl sulfoxide monosolvate, [Fe(C5H5)(C24H27O2)]·C2H6OS, has been synthesized and structurally characterized by single-crystal X-ray diffraction techniques. The mol-ecule crystallizes in the space group P21 with one mol-ecule of dimethyl sulfoxide. A hydrogen bond links the phenol group and the dimethyl sulfoxide O atom, with an O⋯O distance of 2.655 (5) Å. The ferrocene group is positioned in the β face of the estrone moiety, with an O-C-C-C torsion angle of 44.1 (5)°, and the carbonyl bond length of the hormone moiety is 1.216 (5) Å, typical of a C=O double bond. The average Fe-C bond length of the substituted Cp ring [Fe-C(Cp*)] is similar to that of the unsubstituted one [Fe-C(Cp)], i.e. 2.048 (3) versus 2.040 (12) Å. The structure of the complex is compared with those of estrone and eth-oxy-methyl-estrone.

| S-EPMC4908549 | biostudies-literature

1,3,5-Tri-p-tolyl-pentane-1,5-diol.

Project description:In the title compound, C26H30O2, the central benzene ring forms dihedral angles of 14.85 (15) and 28.17 (14)° with the terminal benzene rings. The dihedral angle between the terminal benzene rings is 32.14 (13)°. The crystal packing exhibits two strong inter-molecular O-H⋯O hydrogen bonds, forming directed four-membered co-operative rings. A region of disordered electron density, most probably disordered ethyl acetate solvent mol-ecules, occupying voids of ca 519 Å(3) for an electron count of 59, was treated using the SQUEEZE routine in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155]. Their formula mass and unit-cell characteristics were not taken into account during refinement. The structure was refined as an inversion twin [absolute structure parameter = -0.3 (4)].

| S-EPMC3998290 | biostudies-literature

3-Ferrocenyl-estra-1,3,5 (10)-triene-17-one: Synthesis, Crystal Structure, Hirshfeld Surface Analysis, DFT Studies, and Its Binding to Human Serum Albumin Studied through Fluorescence Quenching and In Silico Docking Studies.

Project description:3-ferrocenyl-estra-1,3,5 (10)-triene-17-one (2), [Fe(C5H5)(C24H25O3)], crystallizes in the monoclinic space group C2. The cyclopentadienyl (Cp) rings adopt a nearly eclipsed conformation, and the Cp plane is tilted by 87.66° with respect to the substituted phenyl plane. An average Fe-C(Cp) bond length of 2.040(13) Å was determined, similar to the one reported for ferrocene. Hirshfeld surfaces and two-dimensional fingerprint plots were generated to analyze weak intermolecular C-H···π and C-H···O interactions. Density functional theory studies revealed a 1.15 kcal/mol rotational barrier for the C3-O1 single bound. Fluorescence quenching studies and in silico docking studies suggest that human serum albumin forms a complex with 2 via a static mechanism dominated by van der Waals interactions and hydrogen bonding interactions.

| S-EPMC10458889 | biostudies-literature

6-Methyl-1,3,5-triazine-2,4-diamine butane-1,4-diol monosolvate.

Project description:The title co-crystal, C4H7N5·C4H10O2, crystallizes with one mol-ecule of 6-methyl-1,3,5-triazine-2,4-diamine (DMT) and one mol-ecule of butane-1,4-diol in the asymmetric unit. The DMT mol-ecules form ribbons involving centrosymmetric R2(2)(8) dimer motifs between DMT mol-ecules along the c-axis direction. These ribbons are further hydrogen bonded to each other through butane-1,4-diol, forming sheets parallel to (121).

| S-EPMC3588973 | biostudies-literature

10-Phenyl-10<i>H</i>-phenoxazine-4,6-diol tetra-hydro-furan monosolvate.

Project description:In the crystalline state of the title solvate, C18H13NO3·C4H8O, hydrogen-bonding inter-actions between hydroxyl groups on a phenoxazine backbone and the tetra-hydro-furan solvent are observed that suggest the ability for this compound to act as a chelating ligand. The O⋯O donor-acceptor distances for this hydrogen bonding are 2.7729 (15) and 2.7447 (15) Å. The three-ring backbone of the phenoxazine bends out of planarity by 18.92 (3)°, as computed using mean planes that encompass each half of the three-ring structure, with the central N and O atoms forming the line of flexion. In the crystal, a π-π stacking arrangement exists between inversion-related mol-ecules, with a centroid-to-centroid distance of 3.6355 (11) Å. In the disordered tetra-hydro-furan solvate, all atoms except oxygen were modeled over two positions, with occupancies of 0.511 (8) and 0.489 (8).

| S-EPMC9462277 | biostudies-literature

1,3,5-Triaryl-1,3,5-Triazinane-2,4,6-Trithiones: Synthesis, Electronic Structure and Linear Optical Properties.

Project description:The synthesis of four new 1,3,5-triaryl-1,3,5-triazinane-2,4,6-trithione derivatives (thioisocyanurates) and two new partially thionated analogues from the corresponding 1,3,5-triaryl-1,3,5-triazinane-2,4,6-triones (isocyanurates) is reported, together with their spectroscopic properties. DFT calculations and comparison with the corresponding isocyanurates evidence the impact of the oxygen-for-sulfur replacement on the electronic structure and linear optical properties of these heterocycles. A bathochromic shift of the absorption bands and more efficient quenching of the fluorescence was observed.

| S-EPMC7700228 | 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