Browse
Submit Data
Databases
API
Help

Dataset Information

12 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone: A convenient synthesis, antiproliferation activity, structure-activity relationships, and role of heterocyclic moiety.

ABSTRACT: A series of steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone were designed and prepared by a convenient heterocyclization reaction. The in vitro anticancer activities for these obtained compounds were evaluated against human cancer cell lines (HepG2, Huh-7, and SGC-7901), which demonstrated that some of these heterocyclic pyrimidine derivatives exhibited significantly good cytotoxic activities against all tested cell lines compared with 5-fluorouracil (5-FU), especially, compound 3b exhibited high potential growth inhibitory activities against all tested cell lines with the IC₅₀ values of 5.41?±?1.34, 5.65?±?1.02 and 10.64?±?1.49??M, respectively, which might be used as promising lead scaffold for discovery of novel anticancer agents.

SUBMITTER: Ke S

PROVIDER: S-EPMC5349525 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone: A convenient synthesis, antiproliferation activity, structure-activity relationships, and role of heterocyclic moiety.

Ke Shaoyong S Shi Liqiao L Zhang Zhigang Z Yang Ziwen Z

Scientific reports 20170314

A series of steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone were designed and prepared by a convenient heterocyclization reaction. The in vitro anticancer activities for these obtained compounds were evaluated against human cancer cell lines (HepG2, Huh-7, and SGC-7901), which demonstrated that some of these heterocyclic pyrimidine derivatives exhibited significantly good cytotoxic activities against all tested cell lines compared with 5-fluorouracil (5-FU), especially, compoun ...[more]

PMID: 28290501

Similar Datasets

Peptidomimetics Based On Dehydroepiandrosterone Scaffold: Synthesis, Antiproliferation Activity, Structure-Activity Relationship, and Mechanisms.

Project description:A series of novel peptidomimetics bearing dehydroepiandrosterone moiety were designed, synthesized, and evaluated for their inhibition activities against cell proliferation. According to the preliminary studies on inhibitory activities, some of the newly prepared compounds indicated significantly inhibition activities against human hepatoma cancer (HepG2), human lung cancer (A549), human melanoma (A875) cell lines compared with the control 5-fluorouracil. Especially, compounds Ii (IC50?<?14??M) and Ik (IC50?<?13??M) exhibited obvious inhibition activities against all tested cell lines. The highly potential compound Ik induced apoptosis in HepG2 cells were analyzed by flow cytometry, and the apoptotic effects of compound Ik were further evaluated using Annexin V-FITC/propidium iodide dual staining assay, which revealed these highly potential compounds induced cell death in HepG2 cells at least partly by apoptosis.

| S-EPMC5009342 | biostudies-literature

The catalytic activity of mycelial fungi towards 7-oxo-DHEA - an endogenous derivative of steroidal hormone dehydroepiandrosterone.

Project description:Seventeen species of fungi belonging to thirteen genera were screened for the ability to carry out the transformation of 7-oxo-DHEA (7-oxo-dehydroepiandrosterone). Some strains expressed new patterns of catalytic activity towards the substrate, namely 16β-hydroxylation (Laetiporus sulphureus AM498), Baeyer-Villiger oxidation of ketone in D-ring to lactone (Fusicoccum amygdali AM258) and esterification of the 3β-hydroxy group (Spicaria divaricata AM423). The majority of examined strains were able to reduce the 17-oxo group of the substrate to form 3β,17β-dihydroxy-androst-5-en-7-one. The highest activity was reached with Armillaria mellea AM296 and Ascosphaera apis AM496 for which complete conversion of the starting material was achieved, and the resulting 17β-alcohol was the sole reaction product. Two strains of tested fungi were also capable of stereospecific reduction of the conjugated 7-keto group leading to 7β-hydroxy-DHEA (Inonotus radiatus AM70) or a mixture of 3β,7α,17β-trihydroxy-androst-5-ene and 3β,7β,17β-trihydroxy-androst-5-ene (Piptoporus betulinus AM39). The structures of new metabolites were confirmed by MS and NMR analysis. They were also examined for their cholinesterase inhibitory activity in an enzymatic-based assay in vitro test.

| S-EPMC8449666 | biostudies-literature

Potential of Steroidal Alkaloids in Cancer: Perspective Insight Into Structure-Activity Relationships.

Project description:Steroidal alkaloids contain both steroidal and alkaloid properties in terms of chemical properties and pharmacological activities. Due to outstanding biological activities such as alkaloids and similar pharmacological effects to other steroids, steroidal alkaloids have received special attention in anticancer activity recently. Substituted groups in chemical structure play markedly important roles in biological activities. Therefore, the effective way to obtain lead compounds quickly is structural modification, which is guided by structure-activity relationships (SARs). This review presents the SAR of steroidal alkaloids and anticancer, including pregnane alkaloids, cyclopregnane alkaloids, cholestane alkaloids, C-nor-D-homosteroidal alkaloids, and bis-steroidal pyrazine. A summary of SAR can powerfully help to design and synthesize more lead compounds.

| S-EPMC8489381 | biostudies-literature

<i>N</i>-Heterocyclic Carbene-Platinum Complexes Featuring an Anthracenyl Moiety: Anti-Cancer Activity and DNA Interaction.

Project description:A platinum (II) complex stabilized by a pyridine and an N-heterocyclic carbene ligand featuring an anthracenyl moiety was prepared. The compound was fully characterized and its molecular structure was determined by single-crystal X-ray diffraction. The compound demonstrated high in vitro antiproliferative activities against cancer cell lines with IC50 ranging from 10 to 80 nM. The presence of the anthracenyl moiety on the N-heterocyclic carbene (NHC) Pt complex was used as a luminescent tag to probe the metal interaction with the nucleobases of the DNA through a pyridine-nucleobase ligand exchange. Such interaction of the platinum complex with DNA was corroborated by optical tweezers techniques and liquid phase atomic force microscopy (AFM). The results revealed a two-state interaction between the platinum complex and the DNA strands. This two-state behavior was quantified from the different experiments due to contour length variations. At 24 h incubation, the stretching curves revealed multiple structural breakages, and AFM imaging revealed a highly compact and dense structure of platinum complexes bridging the DNA strands.

| S-EPMC6747518 | biostudies-literature

A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines.

Project description:An efficient one-pot synthesis of pyrazolo[3,4-d]pyrimidine derivatives by the four-component condensation of hydrazines, methylenemalononitriles, aldehydes and alcohols has been developed via two different reaction pathways. The structures of target products were characterized by IR spectroscopy, NMR ((1)H and (13)C) spectroscopy and HRMS (ESI) spectrometry. The crystal structure of 4-ethoxy-6-(2-nitrophenyl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine was determined by single crystal X-ray diffraction.

| S-EPMC4660965 | biostudies-literature

Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents against Hormone-Dependent Breast Cancer Cells.

Project description:Most breast and prostate tumors are hormone-dependent, making it possible to use hormone therapy in patients with these tumors. The design of effective endocrine drugs that block the growth of tumors and have no severe side effects is a challenge. Thereupon, synthetic steroids are promising therapeutic drugs for the treatment of diseases such as hormone-dependent breast and prostate cancers. Here, we describe novel series of steroidal pyrimidines and dihydrotriazines with anticancer activities. A flexible approach to unknown pyrimidine and dihydrotriazine derivatives of steroids with selective control of the heterocyclization pattern is disclosed. A number of 18-nor-5?-androsta-2,13-diene[3,2-d]pyrimidine, androsta-2-ene[3,2-d]pyrimidine, ?1, 3, 5(10)-estratrieno[16,17-d]pyrimidine, and 17-chloro-16-dihydrotriazine steroids were synthesized by condensations of amidines with ?-chlorovinyl aldehydes derived from natural hormones. The synthesized compounds were screened for cytotoxicity against breast cancer cells and showed IC50 values of 7.4 ?M and higher. Compounds were tested against prostate cancer cells and exhibited antiproliferative activity with IC50 values of 9.4 ?M and higher comparable to that of cisplatin. Lead compound 4a displayed selectivity in ER?-positive breast cancer cells. At 10 ?M concentration, this heterosteroid inhibited 50% of the E2-mediated ER? activity and led to partial ER? down-regulation. The ER? reporter assay and immunoblotting were supported by the docking study, which showed the probable binding mode of compound 4a to the estrogen receptor pocket. Thus, heterosteroid 4a proved to be a selective ER? modulator with the highest antiproliferative activity against hormone-dependent breast cancer and can be considered as a candidate for further anticancer drug development. In total, the synthesized heterosteroids may be considered as new promising classes of active anticancer agents.

| S-EPMC5767602 | biostudies-literature

Structure-activity relationships for hydroxylated polychlorinated biphenyls as inhibitors of the sulfation of dehydroepiandrosterone catalyzed by human hydroxysteroid sulfotransferase SULT2A1.

Project description:Polychlorinated biphenyls (PCBs) are persistent worldwide pollutants that are of concern due to their bioaccumulation and health effects. Metabolic oxidation of PCBs results in the formation of hydroxylated metabolites (OHPCBs). Among their biological effects, OHPCBs have been shown to alter the metabolism of endocrine hormones, including inhibition of mammalian cytosolic sulfotransferases (SULTs) that are responsible for the inactivation of thyroid hormones and phenolic steroids (i.e., hSULT1A1, hSULT1B1, and hSULT1E1). OHPCBs also interact with a human hydroxysteroid sulfotransferase that plays a role in the sulfation of endogenous alcohol-containing steroid hormones and bile acids (i.e., hSULT2A1). The objectives of our current study were to examine the effects of a series of OHPCB congeners on the activity of hSULT2A1 and to develop a three-dimensional quantitative structure-activity relationship (3D-QSAR) model for OHPCBs as inhibitors of the enzyme. A total of 15 OHPCBs were examined, and the sulfation of 1 ?M [(3)H] dehydroepiandrosterone (DHEA) was utilized as a model reaction catalyzed by the enzyme. All 15 OHPCBs inhibited the sulfation of DHEA, with IC(50) values ranging from 0.6 ?M to 96 ?M, and eight of these OHPCBs were also substrates for the enzyme. Comparative molecular field analysis (CoMFA) provided a predictive 3D-QSAR model with a q(2) value of 0.697 and an r(2) value of 0.949. The OHPCBs that had the highest potency as inhibitors of DHEA sulfation were those with a 3, 5-dichloro-4-hydroxy substitution pattern on the biphenyl ring system, and these congeners were also substrates for sulfation catalyzed by hSULT2A1.

| S-EPMC3196794 | biostudies-literature

N-Heterocyclic Carbenes Derived from Guanosine: Synthesis and Evidences of Their Antiproliferative Activity.

Project description:Palladium(II) and platinum(II) complexes bearing N-heterocyclic carbenes derived from guanosine are synthesized via oxidative addition, followed by protonation in the presence of acid. Cytotoxicity of the compounds is evaluated in several cell lines. Compounds 2a, 2b, and 3a are selective for glioblastoma U251 cells and are nontoxic toward healthy human embryonic kidney (HEK293) cells.

| S-EPMC6288774 | biostudies-literature

A convenient and practical synthesis of ?-diketones bearing linear perfluorinated alkyl groups and a 2-thienyl moiety.

Project description:A versatile and robust synthetic protocol for the preparation of ?-diketones bearing 2-thienyl and perfluorinated alkyl radicals of different length or a methyl group was developed. This protocol is suitable for the preparation of multigram quantities of diketones without cumbersome purification procedures. Moreover, the known method for purification of diketones via copper chelates was improved considerably.

| S-EPMC6317410 | biostudies-literature

Decisive interactions between the heterocyclic moiety and the cluster observed in polyoxometalate-surfactant hybrid crystals.

Project description:Inorganic-organic hybrid crystals were successfully obtained as single crystals by using polyoxotungstate anion and cationic dodecylpyridazinium (C12pda) and dodecylpyridinium (C12py) surfactants. The decatungstate (W10) anion was used as the inorganic component, and the crystal structures were compared. In the crystal comprising C12pda (C12pda-W10), the heterocyclic moiety directly interacted with W10, which contributed to a build-up of the crystal structure. On the other hand, the crystal consisting of C12py (C12py-W10) had similar crystal packing and molecular arrangement to those in the W10 crystal hybridized with other pyridinium surfactants. These results indicate the significance of the heterocyclic moiety of the surfactant to construct hybrid crystals with polyoxometalate anions.

| S-EPMC4425093 | 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