Abstract：
:A new series of thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyphenyl) moiety were synthesized as diaryl-heterocylic analogs of combretastatin A-4 with anticancer activity. The cytotoxicity evaluation of synthesized compounds against cancer cell lines (A549, MCF-7 and SKOV3) revealed that most of them had potent cytotoxic activity toward all tested cell lines (IC50s < 10 μg/mL). Among them, 3-(chlorobenzyl) derivatives 5c and 5d showed the best inhibitory effect on MCF-7 cells (IC50 values of 1.14 and 2.41 μg/mL, respectively). Furthermore, the ability of tubulin polymerization inhibition and apoptosis induction were evaluated for the promising compounds 5c and 5d. Results suggested that these compounds remarkably inhibit tubulin polymerization and induce apoptosis resulting in cell death. In vitro studies revealed that these compounds had no significant cytotoxicity against normal cells at the concentrations required for growth inhibition of cancer cells. In vitro biding assay and in silico docking study also confirmed the binding of prototype compound to the colchicine binding site of tubulin.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Ansari M,Shokrzadeh M,Karima S,Rajaei S,Fallah M,Ghassemi-Barghi N,Ghasemian M,Emami Sdoi
10.1016/j.ejmech.2019.111784subject
Has Abstractpub_date
2020-01-01 00:00:00pages
111784eissn
0223-5234issn
1768-3254pii
S0223-5234(19)30936-5journal_volume
185pub_type
杂志文章abstract：:A series of novel rutaecarpine derivatives and related alkaloid derivatives 3-aminoalkanamido-substituted rutaecarpine 4a-f and 7,8-dehydrorutaecarpine 5a-c, and 6-aminoalkanamido-substituted 3-[2-(3-Indolyl)ethyl]-4(3a)-quinazolinones 8a-c, were synthesized and subjected to pharmacological evaluation as acetylcholine...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2009.12.044
更新日期：2010-04-01 00:00:00
abstract：:We report a convenient synthesis of carbazole-1,4-quinone alkaloid koeniginequinones A and B using a tandem ring-closing metathesis with the dehydrogenation reaction sequence under an O2 atmosphere as an important step. Using this method, carbazole-1,4-quinones substituted at the 5-, 6-, 7-, and/or 8-positions have be...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.05.065
更新日期：2016-10-04 00:00:00
abstract：:Inhibition data on rat monoamine oxidase B isoform of a large number of 7-metahalobenzyloxy-2H-chromen-2-one derivatives (67 compounds) carrying at position 4 a variety of substituents differing in steric, electrostatic, lipophilic and H-bonding properties, were modeled by Gaussian field-based 3D-QSAR and docking simu...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.10.029
更新日期：2015-01-07 00:00:00
abstract：:A series of tocopherol-based cationic lipid 3a-3f bearing a pH-sensitive imidazole moiety in the dipeptide headgroup and a reduction-responsive disulfide linkage were designed and synthesized. Acid-base titration of these lipids showed good buffering capacities. The liposomes formed from 3 and co-lipid 1, 2-dioleoyl-s...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2017.02.010
更新日期：2017-03-31 00:00:00
abstract：:Seventeen tetrahydroisoquinoline derivatives were designed, synthesized and evaluated for inhibition of NO production in lipopolysaccharide-stimulated BV-2 microglial cells. Compounds 5a, 9c and 11a potently attenuated NO production by >60%, and 5a and 11a inhibited BH4 production by >48% at 100 microM. In particular,...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2007.09.009
更新日期：2008-06-01 00:00:00
abstract：:In this study, we used a solution of FeCl(3) in THF to facilitate the Mannich-type reaction of aldehyde, amine and phosphite compounds to form corresponding alpha-aminophosphonates in a one-pot, three-component reaction. Selected alpha-aminophosphonates were entered into a biological assay test and were studied by doc...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2009.07.009
更新日期：2009-11-01 00:00:00
abstract：:The use of nitroreductases (NTR) that catalyze the reduction of nitro compounds by using NAD(P)H in GDEPT (Gene-directed enzyme prodrug therapy) studies which minimize toxicity at healthy cells and increases concentration of drugs at cancer cells is remarkable. Discovery of new prodrug/NTR combinations is necessary to...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2019.03.035
更新日期：2019-06-01 00:00:00
abstract：:We here describe the preparation of a series of hybrid molecules containing a combretastatin A-4 moiety and a pironetin analogue fragment connected through a spacer of variable length which includes a 1,2,3-triazole ring. The cytotoxic activities of these compounds have been measured. Relations between structure and c...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.09.053
更新日期：2014-11-24 00:00:00
abstract：:Oxindole has emerged as a valuable scaffold in medicinal chemistry possessing diverse range of pharmacological activities. Its value has further been increased by its natural occurrence as alkaloids in variety of plants. It was first extracted from the cat claw's plant Uncaria tomentosa found in the Amazon rainforest ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.ejmech.2016.08.011
更新日期：2016-11-10 00:00:00
abstract：:Explorations into modeling human oral bioavailability started with a whole dataset of 772 drug compounds. First, training set and test set were chosen based on Kohonen's self-organizing Neural Network (KohNN). Then, a quantitative model of the whole dataset was built using multiple linear regression (MLR) analysis. Th...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2008.05.017
更新日期：2008-11-01 00:00:00
abstract：:N-arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) wi...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2010.09.057
更新日期：2010-12-01 00:00:00
abstract：:A new quinazolone series has been designed, and synthesized by the anthranilic acid and different acid derivatives. Their structures have been elucidated on the basis of elemental analyses and spectral studies (IR, (1)H NMR, FT-IR and FAB-MS). A preliminary radiolabelling study with technetium has shown a very good fu...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2007.01.002
更新日期：2007-09-01 00:00:00
abstract：:In a wide search program towards new and efficient antimicrobial agents, a series of 40 substituted chalcones have been synthesized and tested for their in vitro antibacterial and antifungal activities. The structures of these compounds have been investigated by nuclear magnetic resonance spectroscopy and mass spectro...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2007.05.006
更新日期：2008-04-01 00:00:00
abstract：:A series of novel indole derivatives was designed and synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase). The most potent compound 14c was identified with an IC50 value of 0.10 μM by testing the inhibitory activity against recombinant human FBPase. The structure-activity relationships were investigated ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.11.049
更新日期：2015-01-27 00:00:00
abstract：:The absorption of 111 drug and drug-like compounds was evaluated from 111 references based on the ratio of urinary excretion of drugs following oral and intravenous administration to intact rats and biliary excretion of bile duct-cannulated rats. Ninety-eight drug compounds for which both human and rat absorption data...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0223-5234(03)00015-1
更新日期：2003-03-01 00:00:00
abstract：:In the human cell cycle, the Myt1 kinase is a crucial regulator of the G2/M transition. Because this membrane-associated kinase is hard to obtain and assay, there is a distinct lack of data so far. Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2012.06.007
更新日期：2013-03-01 00:00:00
abstract：:Sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors are the current focus on the indication for the management of hyperglycemia in diabetes. Here, a novel series of C-linked indolylxyloside-based inhibitors of SGLT2 has been discovered. Structure-activity relationship studies revealed that substituents at the...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2012.06.053
更新日期：2012-09-01 00:00:00
abstract：:Synthesis of a series of urea/thiourea/acetamide/sulphonamide derivatives of quinazolinones conjugated lysine has been reported. Structures of the products have been determined by standard spectroscopical studies. All the compounds have been screened for their antibacterial studies and structure-activity relationship ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2011.03.041
更新日期：2011-06-01 00:00:00
abstract：:Twenty four compounds with diversified 3-aryl acrylic amide side chains of the simplified saframycin-ecteinascidin pentacyclic skeleton were synthesized via a 14-step stereospecific route starting from L-dopa. The cytotoxicities of these compounds were tested against eight human tumor cell lines including HCT-8, BEL-7...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2013.01.033
更新日期：2013-04-01 00:00:00
abstract：:Phosphonocarboxylate (PC) analogs of the anti-osteoporotic drugs, bisphosphonates, represent the first class of selective inhibitors of Rab geranylgeranyl transferase (RabGGTase, RGGT), an enzyme implicated in several diseases including ovarian, breast and skin cancer. Here we present the synthesis and biological char...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.06.062
更新日期：2014-09-12 00:00:00
abstract：:The re-emergence of tuberculosis (TB) as a global health problem over the past few decades, accompanied by the rise of drug-resistant strains of Mycobacterium tuberculosis, emphasizes the need for discovery of new therapeutic drugs against this disease. The emerging serious problem both in terms of TB control and clin...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2008.04.013
更新日期：2009-02-01 00:00:00
abstract：:2-(5-Arylfurfurylidene/5-nitrofurfurylidene)-5-aryl-7-(2,4-dichloro-5-fluorophenyl)-5H-thiazolo[2,3-b]-pyrimidin-2(1H)-ones 5 and 6 are synthesized by a novel three component reaction of 4,6-diarylpyrimidino-2(1H)-thiones 4, monochloroacetic acid, arylfurfuraldehydes and 5-nitro-2-furfuraldenediacetate, respectively. ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2004.06.001
更新日期：2004-09-01 00:00:00
abstract：:Asiatic acid (AA) derivatives 4 and 5 modified at the C-11 and C-28 positions were designed and synthesized, their structures were confirmed using HRMS, (1)H NMR and (13)C NMR. In vitro antitumor activities of all compounds against MGC-803, NCI-H460, HepG2, Hela and 7404 cancer cell lines were evaluated and compared w...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.08.003
更新日期：2014-10-30 00:00:00
abstract：:A new series of indolo[1,2-c]quinazoline derivatives were prepared in good yield through reaction of 2-(o-aminophenyl)indole with a variety of arylaldehydes. The structures of the newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR and mass spectral studies and elemental analysis. All the title compo...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2009.11.038
更新日期：2010-03-01 00:00:00
abstract：:Derived from the structures of the alkaloids rutaecarpine and dehydroevodiamine (DHED), and the long-known acetylcholinesterase (AChE) inhibitor tacrine, respectively, novel compounds were synthesised, including: 13-methyl-5,8-dihydro-6H-isoquino[1,2-b]quinazolin-13-ium chloride (12), (8Z)-5,6-dihydro-8H-isoquino[1,2-...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2004.12.003
更新日期：2005-03-01 00:00:00
abstract：:Twenty-six naturally occurring oleanolic acid saponins and their derivatives, 16 of which were synthesized in this study, were preliminarily evaluated against human cancer cells. From SAR studies, the presence of α-l-rhamnosyl residue at the terminal of both C-3 and C-28 position for oleanolic acid bidesmosides was im...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2013.04.016
更新日期：2013-06-01 00:00:00
abstract：:Five series of thiourea derivatives bearing benzothiazole moiety (20 compounds) were efficiently synthesized and evaluated for antimicrobial and anticancer activities. The results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms and showed higher activity against fu...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2009.12.016
更新日期：2010-04-01 00:00:00
abstract：:A new series of substituted 8-fluro-4H-pyrimido[2,1-b] [1,3]benzothiazole-4-ones () substituted 7-methyl-4H-isoxazolo[2,3-a]pyrimidin-4-ones, and substituted 2-methyl-5,6,7,8-tetrahydro-9H-isoxazolo[2,3-a]pyridopyrimidin-9-ones, compounds I-VII, have been prepared via condensation of beta-keto esters with 2-aminopyrid...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2006.03.025
更新日期：2006-08-01 00:00:00
abstract：:The effect of double asymmetric induction for the synthesis of new cis-β-lactams by [2 + 2] cycloaddition reactions of chiral imines with a chiral ketene was investigated. The cycloaddition reaction was found to be totally diastereoselective leading exclusively to the formation of the cis-β-lactam derivatives. The new...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.09.077
更新日期：2014-11-24 00:00:00
abstract：:Purple acid phosphatases (PAPs) are binuclear hydrolases that catalyze the hydrolysis of phosphorylated substrates under acidic to neutral conditions. Elevated serum concentrations of PAP are observed in patients suffering from osteoporosis, identifying this enzyme as a potential target for the development of novel th...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2019.111611
更新日期：2019-11-15 00:00:00
