Abstract:
:There is much interest in the use of phytoestrogens such as coumestrol in breast cancer intervention due to their antiestrogenic activity and multiple modes of tumor cell death. However, the clear beneficial effects of naturally occurring estrogen mimetic coumestrol remain controversial due to experimental evidence that it has been shown to stimulate MCF-7 cell proliferation via agonist effect on estrogen receptor at low concentration. Herein, to disconnect the ER interaction and apoptosis-specific mechanism of coumestrol, various 3, 9-di-O-substituted coumestrols (7a-7e) and their furan ring-opened analogs (5a-5e) were synthesized and assessed for antiproliferative properties. Attachment of a dimethylamine-containing side chain to 3-O of coumestrol led to the most promising compound 7e with improved antiproliferative activity (1.7-fold increase) against MCF-7 cells, decreased estrogen activity (>20 times weaker ERα binder) and a novel action to induce apoptosis. Mechanistic studies revealed that 7e is a tubulin polymerization inhibitor, which could arrest cell cycle at G2/M phase and induce apoptosis along with the decrease of mitochondrial membrane potential. In summary, such subtle modifications to the 3, 9-di-hydroxyl groups of coumestrol allow the generation of a novel apoptosis inducer with distinct pharmacological properties, providing an excellent starting point to future development of novel tumor-vascular disrupting agents targeting tubulin.
journal_name
Bioorg Chemjournal_title
Bioorganic chemistryauthors
Luo G,Tang Z,Li X,Hou Q,Chen Y,Lao K,Xiang Hdoi
10.1016/j.bioorg.2018.12.024subject
Has Abstractpub_date
2019-04-01 00:00:00pages
140-151eissn
0045-2068issn
1090-2120pii
S0045-2068(18)30920-9journal_volume
85pub_type
杂志文章abstract::This work aimed to evaluate the inhibition of Candida rugosa lipase by five guanylhydrazone derivatives through biological, biophysical and theoretical studies simulating physiologic conditions. The compound LQM11 (IC50 = 14.70 μM) presented the highest inhibition against the enzyme. Therefore, for a better understand...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.03.030
更新日期:2019-06-01 00:00:00
abstract::GyrB and ParE are type IIA topoisomerases and found in most bacteria. Its function is vital for DNA replication, repair and decatenation. The highly conserved ATP-binding subunits of DNA GyrB and ParE are structurally related and have been recognized as prime candidates for the development of dual-targeting antibacter...
journal_title:Bioorganic chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.bioorg.2015.07.004
更新日期:2015-10-01 00:00:00
abstract::The overexpression of P-glycoprotein plays an important role in the process of multidrug resistance (MDR). P-gp inhibitors are one of the effective strategies to reverse tumor MDR. Novel P-gp inhibitors with phthalazinone scaffolds were designed, synthesized and evaluated. Compound 26 was found to be the most promisin...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.01.039
更新日期:2019-05-01 00:00:00
abstract::In the current study, a series of novel 1,2,4-triazol-3-amine derivatives were designed, synthesized, and biologically evaluated in vivo for their anticonvulsant and hypnotic effects in the pentylenetetrazole (PTZ)-induced seizures, maximal electroshock (MES)-induced seizures, and pentobarbital-induced sleeping tests....
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104212
更新日期:2020-11-01 00:00:00
abstract::The reactions of a ribonuclease model substrate, the compound uridine-3'-p-nitrophenyl phosphate, have been examined using heavy-atom isotope effects and stereochemical analysis. The cyclization of this compound is subject to catalysis by general base (by imidazole buffer), specific base (by carbonate buffer), and by ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1006/bioo.2000.1170
更新日期:2000-06-01 00:00:00
abstract::Suppression of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) along with nitric oxide reduction in RAW 264.7 cells by 7,8-dihydroxy-4-methylcoumarin, ethyl p-coumarate, ethyl caffeate and ethyl ferulate drove us to search structural-analogues of the aforementioned compounds through structure-based drug design. Doc...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.102991
更新日期:2019-08-01 00:00:00
abstract::Levels of cAMP that control critical platelet functions are regulated by cGMP-inhibited cAMP phosphodiesterase (PDE3A). We previously showed that millimolar concentrations of the hydrolyzable 8-[(4-bromo-2,3-dioxobutyl)thioadenosine 3',5'-cyclic monophosphate (8-BDB-TcAMP) inactivate PDE3A. We have now synthesized a n...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1006/bioo.2001.1226
更新日期:2002-02-01 00:00:00
abstract::A series of benzimidazole-oxindole conjugates were synthesized and evaluated for their cytotoxic activity. The cytotoxicity assay results suggest that conjugates 5c and 5p exhibit promising cytotoxicity against human breast cancer cell line (MCF-7). The Cell cycle analysis revealed that these conjugates induced cell c...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2015.09.003
更新日期:2015-12-01 00:00:00
abstract::Many artemisinin derivatives have good inhibitory effects on malignant tumors. In this work, a novel series of artemisinin derivatives containing piperazine and fluorine groups were designed and synthesized and their structures were confirmed by 1H NMR, 13C NMR and HRMS technologies. The in vitro cytotoxicity against ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104496
更新日期:2021-01-01 00:00:00
abstract::Five previously undescribed 4,5-seco-abietane rearrange diterpenoids (1-5, Prionidipene A-E) were isolated from the aerial parts of Salvia prionitis, along with thirteen known seco-abietane diterpenoids (6-18). The structures of 1-5 were elucidated mainly based on analysis of NMR and MS data. The absolute configuratio...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.08.040
更新日期:2018-12-01 00:00:00
abstract::New thiophene (2-13) and thienopyrimidine (15-27) derivatives have been synthesized. Twenty three compounds were screened against five cell lines namely; hepatocellular carcinoma (liver) HepG-2, epidermoid carcinoma (larynx) Hep-2, mammary gland (breast) MCF-7, human prostate cancer PC-3 and epithelioid cervix carcino...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.09.022
更新日期:2018-12-01 00:00:00
abstract::A class of 3-substituted 1H-pyrrolo[2,3-b]pyridine derivatives were designed, synthesized and evaluated for their in vitro biological activities against maternal embryonic leucine zipper kinase (MELK). Among these derivatives, the optimized compound 16h exhibited potent enzyme inhibition (IC50 = 32 nM) and excellent a...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103474
更新日期:2020-01-01 00:00:00
abstract::Drug resistance and cancer cells metastasis have been the leading causes of chemotherapy failure and cancer-associated death in breast cancer patients. In present, various active molecules either exhibiting novel mechanism of action such as inducing autophagy or inhibiting metastasis have been developed to address the...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.11.025
更新日期:2019-03-01 00:00:00
abstract::A series of new 1,2,3-triazole linked coumarinopyrazole conjugates 4a-e and 5a-e have been synthesized via the Copper(I)-catalysed Alkyne-Azide Cycloaddition (CuAAC). Going through the reaction of compound 2 with the 3-propargyl bromide gave a mixture of propargylated regioisomers 3 + 3' used as a dipolarophile to acc...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.06.005
更新日期:2018-10-01 00:00:00
abstract::Analkali tolerant α-l-rhamnosidase has been purified to homogeneity from the culture filtrate of a new fungal strain, Fusarium moniliforme MTCC-2088, using concentration by ultrafiltration and cation exchange chromatography on CM cellulose column. The molecular mass of the purified enzyme has been found to be 36.0 kDa...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.11.027
更新日期:2019-03-01 00:00:00
abstract::Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. I...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.102937
更新日期:2019-07-01 00:00:00
abstract::As a part of our continuing search for bioactive constituents from Brassicaceae family, three new bis-thioglycosides (1-3) were isolated from the 80% MeOH extract of Nasturtium officinale, together with 13 known compounds (4-16). The chemical structures of three new bis-thioglycosides (1-3) were elucidated using NMR t...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.01.062
更新日期:2019-05-01 00:00:00
abstract::Suntamide A (1), a new cyclic peptide, was isolated from Cicadidae Periostracum. The gross structure of 1 was elucidated by detailed analysis of HRMS and 1D/2D NMR spectra, and the absolute configuration was established by C3 Marfey's method. We extended our study to examine biological activity of 1, and found that 1 ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104493
更新日期:2021-01-01 00:00:00
abstract::Fusicoccane-derived diterpenoids bearing a unique bridgehead double-bond-containing tricyclo[9.2.1.03,7]tetradecane (5-9-5 ring system) core skeleton represent a rarely reported class of rearranged terpenoids, which traced back to fusicoccanes with a classical dicyclopenta[a,d]cyclooctane (5-8-5 ring system) core skel...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.103887
更新日期:2020-07-01 00:00:00
abstract::In this paper, we present our investigation on ribonuclease A (RNase) modifications induced by 1,4-benzoquinone (PBQ), 2-methyl-1,4-benzoquinone (MBQ), and 2-chloro-1,4-benzoquinone (CBQ). The goal of the study was to evaluate quinone-induced protein modifications as well as substituent effects, utilizing several tech...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2015.02.004
更新日期:2015-04-01 00:00:00
abstract::Novel ammonium and betaine derivatives of p-tert-butylthiacalix[4]arene in cone and 1,3-alternate conformation were synthesized with high yields for the first time. The obtained compounds form in water spherical nanoparticles. It was shown by molecular docking calculations and in vitro experiments that amino and betai...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103455
更新日期:2020-01-01 00:00:00
abstract::With the aim of finding new anti-inflammatory drugs, a series of new Glycyrrhetinic acid derivatives (1-34) have been designed and synthesized by structural modification, and their anti-inflammatory activities in vitro have been evaluated. The anti-inflammatory activities assay demonstrated that compound 5b suppressed...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104598
更新日期:2020-12-29 00:00:00
abstract::Xanthatin, a natural sesquiterpene lactone, occurs as one of the major constituents of Xanthium plants (Compositae) and exhibits many important biological properties. To discover natural products-based pesticides, forty-nine Michael-type thiol/amino adducts of xanthatin were synthesized and characterized, while their ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.103696
更新日期:2020-04-01 00:00:00
abstract::In this study, we prepared a novel amino cellulose derivative (benzyl cellulose-g-poly [2-(N,N-Dimethylamino)ethyl methacrylate]) via a homogeneous ATRP method. The successful synthesis of the novel amino cellulose was confirmed by FT-IR and 1H NMR. This study addressed the different characteristics of the prepared po...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104355
更新日期:2021-01-01 00:00:00
abstract::Tuberculosis (TB) is the world's second commonest cause of death next to HIV/AIDS. The increasing emergence of multi drug resistance and the recalcitrant nature of persistent infections pose an additional challenge for the treatment of TB. Due to the development of resistance to conventional antibiotics there is a nee...
journal_title:Bioorganic chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.bioorg.2013.11.004
更新日期:2014-02-01 00:00:00
abstract::Three novel series of s-triazine derivatives, including thirty-five new compounds 2a-d, 3a-3p, 4b-d, 5b-d, 6d-6d, and 7a-7f were synthesized comprising a diversity of substituents based on the structure of Astrazeneca arylaminotriazine DNA gyrase B inhibitor. The antimicrobial activity was determined for all compounds...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103013
更新日期:2019-08-01 00:00:00
abstract::A series of 4-imidazolylflavans having a variety of substituents on the 2-phenyl ring was synthesized and investigated for their inhibitory effect against aromatase. Structure-activity relationships of these compounds were determined. An additional chlorine atom or a cyano group at the 4' position did not enhance arom...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2004.06.008
更新日期:2004-12-01 00:00:00
abstract::Nine new ent-pimarane-type diterpenoids, siegesbeckia A-I (1-9), together with four known analogues ent-3α,15,16,19-tetrahydroxypimar-8(14)-ene (10), 15,16-dihydroxypimar-8(14)-en-3-one (11), 14β,16-epoxy-7-pimarene-3α,15β-diol (12) and darutigenol (13), were obtained from the aerial parts of Siegesbeckia glabrescens ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.103854
更新日期:2020-06-01 00:00:00
abstract::The interaction of the coordination compounds with biological molecules resulted in the investigation of the drug potential of these molecules. In this study, enzyme inhibition of DSA (1-3) coordination compounds that were previously investigated for their anticancer and antibacterial properties was investigated. Also...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104066
更新日期:2020-08-01 00:00:00
abstract::Herein, substituted imidazole-pyrazole hybrids (2a-2n) were prepared via a multi component reaction employing pyrazole-4-carbaldehydes (1a-1d), ammonium acetate, benzil and arylamines as reactants. All the new compounds were characterized through their spectral and elemental analyses. Further these compounds were test...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.10.047
更新日期:2019-02-01 00:00:00