A series of novel N‐(substituted benzyl)‐3,5‐bis(benzylidene)‐4‐piperidones 5a – 5o were synthesized with substituted benzylamines as raw materials via a series of Michael addition, Dieckmann condensation, hydrolysis decarboxylation and aldol condensation. The structures were confirmed by 1H NMR, IR, MS techniques and elemental analysis. Assay‐based antiproliferative activity study using leukemic cell lines K562 revealed that most of the title compounds have high effectiveness in inhibiting leukemia K562 cells proliferation, among which the compounds 5g (IC50=7.81 µg·mL−1), 5k (IC50=6.35 µg·mL−1), 5l (IC50=7.20 µg·mL−1), and 5o (IC50=5.79 µg·mL−1) have better inhibition activities than standard 5‐fluorouracil (IC50=8.56 µg·mL−1). 相似文献
Quercetin, a naturally occurring potent antioxidant, is limited in therapeutic use, owing to its poor water solubility and stability. Herein, a method of conjugating quercetin to an aldehyde functionalized dextran via an HCl catalyzed condensation reaction to yield a water soluble quercetin functionalized polymer is reported. The prepared conjugate is characterized by 1H and 1H‐13C heteronuclear single quantum correlation (HSQC) NMR, which demonstrate that conjugation occurs via both the A‐ and B‐rings of quercetin. The degree of quercetin functionalization can be tuned by varying the reaction temperature and/or the concentration of the HCl catalyst. However, as temperatures and HCl concentrations are increased above 40 °C and 2 m , respectively, the increase in functionalization is accompanied by an increase in the oxidation of the conjugated quercetin and a decrease in polymer yield. The prepared conjugate is shown to have improved stability compared with native quercetin while maintaining substantial free‐radical scavenging activity. Anticancer activity is evaluated in vitro in a neuroblastoma cell line. The dextran–aldehyde–quercetin conjugate prepared at 40 °C and 2 m HCl is shown to be cytotoxic to neuroblastoma cells (SH‐SY5Y–IC50 = 123 µg mL−1 and BE(2)‐C–IC50 = 380 µg mL−1) but shows no activity against nonmalignant MRC‐5 cells at concentrations up to 400 µg mL−1. 相似文献
A new series of tetrahydropyrido[4,3‐d]dihydropyrimidine‐2‐thiones ( 3a–3x ) were designed and synthesized. Their structures were confirmed by 1H NMR, IR, MS and elemental analysis, and the conformation of compound 3j was confirmed by X‐ray diffraction. Preliminary bioassays indicated that most of the target compounds presented good antiproliferative activities against leukemic K562 cells, ovarian cancer HO‐8910 cells and liver cancer SMMC‐7721 cells in vitro. Among them the compounds 3i and 3m afford the best activity, the IC50 of them were 3.22 and 3.65 µg/mL against leukemic K562 cells, respectively, which were lower than the anticancer drug of clinical practice 5‐FU (IC50=8.56 µg/mL). Preliminary mechanism of action studies revealed that compound 3i caused DNA fragmentation and activated caspase‐3/7 in leukemic K562 cells. 相似文献
The title compounds, C16H15BrN3O3+·Cl−·CH4O (WHI–P154) and C16H16N3O3+·Cl− (WHI–P180), are potent inhibitors [WHI–P154 with IC50 = 5.6 µM and WHI–P180 with IC50 = 4.0 µM for epidermal growth factor receptor (EGFR) kinase inhibition] of the EGFR tyrosine kinase as well as Janus Kinase 3. The molecular structures of these compounds are very similar except for the dihedral angle between the anilino and quinazoline moieties which is 1.10 (5)° for WHI–P154, and 45.66 (6) and 25.29 (7)° for the two molecules of WHI–P180 in the asymmetric unit. The nitrogen at the N3 position is protonated in both structures and participates in hydrogen bonding with the chlorine anions. 相似文献
Derivatives (1–15) of steroidal and indole class were synthesized using different strategies. These compounds were characterized by 1H NMR spectroscopy and EI-MS, respectively. The synthetic derivatives were examined for their cytotoxic effects on human adenocarcinoma cells (HCT-116) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and morphometric analysis. The cytotoxic effects of all the compounds were observed after 48 h treatment and it was found that out of fifteen, four compounds 1, 2, 3, and 14 showed inhibitory action on the cancer cells. We have calculated the IC50 values for compounds 1, 2, 3, and 14 which were 22.50 µg/mL, 55.65 µg/mL, 21.35 µg/mL and 58.50 µg/mL, respectively. The compounds 3 (IC50 = 21.35 µg/mL) and 1 (IC50 = 22.50 µg/mL) showed highest inhibitory activities as compared to compounds 2 (IC50 = 55.65 µg/mL) and 14 (IC50 = 58.50 µg/mL). These results suggested that steroidal thiazole and indole derivatives are potent lead molecules having strong anti-cancer proliferative capabilities. 相似文献
Stoichiometric reactions of 4,4'-diacetylcurcumin ( HL ) with series of transition metal ions, namely Fe3+, Co2+, Ni2+ and Zn2+, in methanol result in the corresponding homoleptic metal complexes. All the obtained complexes were characterized by elemental analysis, high resolution mass spectrometry, IR spectroscopy, magnetic moment and single-crystal X-ray diffraction. Structural analyses are unprecedentedly performed for the FeIII, CoII, and NiII complexes and reveal octahedral mononuclear complexes with the compositions [Fe(L)3] and [M(L)2(MeOH)2] (M = Co2+, Ni2+, Zn2+) for trivalent and divalent metal ions, respectively. In all complexes, the deprotonated ligands serve as monoanionic and bidentate ligands with (O,O)-chelating β-diketonate moieties. The free ligand HL exhibits considerable antiproliferative effects for the human MCF-7 breast and HepG2 liver cancer cells with IC50 values of 20.91 ± 2.16 μg · mL–1 and 12.85 ± 1.85 μg · mL–1, respectively. The CoII and ZnII complexes with IC50 values in the range of 14.53–20.80 μg · mL–1 for MCF-7 breast and 8.48–10.68 μg · mL–1 for HepG2 liver cancer cells show stronger antiproliferative effects than HL, the FeIII and NiII complexes cause weaker reductions of the growth of the two tested cancer cell lines. 相似文献
We observed how a change of specific residues in LfcinB dimeric and palindromic sequences caused a notable increase in the cytotoxic activity against CaCo-2 cells while maintaining or even diminishing the level of the cytotoxic effect against normal fibroblast and HEK-293 cells. In both cases, the IC50 of the peptides was reduced by more than half of the concentration, diminishing the IC50 value from 150 µg/mL (101 µM) (LfcinB (21–25)Pal: RWQWRWQWR) to 60 µg/mL (42.8 µM) for the modified palindromic peptide 5[A] LfcinB (21–25)Pal: RWQWAWQWR and the IC50 from 125 µg/mL (LfcinB (20–30)2: (RRWQWRMKKLG)2-K-Ahx to 58 µg/mL (18 µM) for the modified dimeric peptide 26[F] LfcinB (20–30)2: (RRWQWRFKKLG)2-K-Ahx. The cytotoxic effect of 26[F] LfcinB (20–30)2 and LfcinB (21–25)Pal peptides against colon cancer cell line HCT-116 was greater than the cytotoxic effect of these peptides against Caco-2 cells, suggesting that the cytotoxic effect of these peptides is selective for colon cancer cell lines. The cytotoxic effect of the peptides rapidly caused severe damage to the morphology of CaCo-2 cells, while the morphology of the normal fibroblast and HEK-293 cells was not affected. The dimeric modified peptide 26[F] LfcinB (20–30)2 mainly caused death through apoptotic events. As for the palindromic modified peptide 5[A] LfcinB (21–25)Pal, the cell death was induced by both necrotic and apoptotic pathways. All this suggests that specific modification of a single residue in the peptide sequence can improve the anticancer activity of the original monomeric or dimeric peptides, giving place to new potential molecules for the future development of drugs for use against colorectal carcinoma. Our results show that changes to a residue of the anti-cancer peptide sequence may be considered a versatile, feasible, and invaluable strategy for obtaining promising sequences for developing peptide-based cancer treatments. 相似文献
A series of compounds 5‐amino‐2‐ethylmercapto‐4‐phenyl‐6‐subistitutedthieno[2,3‐d]pyrimidines ( 8a–d ), 4‐chloro‐7‐ethylmercapto‐9‐phenylpyrimido[5′,4′:4,5]thieno[3,2‐d]triazine ( 9 ), and 2‐ethylmercapto‐8‐oxo‐4‐phenyl‐7‐(4‐chlorophenyl)pyrimido [4′,5′:4,5]thieno[2,3‐d]pyrimidine ( 10 ) were synthesized and their structures were confirmed by 1H NMR , 13C NMR, and MS . All compounds were evaluated for their IC50 values against three cancer cell lines (MCF ‐7, HUH ‐7 and BHK ) and WISH cells. The IC50 of compound ( 8d ) was calculated for each cell line. Interestingly, the IC50 for the normal human amnion WISH cell line was much higher (723 µg/mL) than those found for the tumor cell lines BHK (17 µg/mL), HUH ‐7 (5.8 µg/mL), and MCF ‐7 (8.3 µg/mL). The proliferation inhibition of normal (WISH ) and tumor (BHK , HUH ‐7, and MCF ‐7) cells by compound ( 8d ) was investigated using MTT assay, and the IC50 was calculated after 48 h of treatment for each cell line. 相似文献
AbstractA new cyclic pentapeptide, pentaminolarin (1), and a new cytochalasin, xylochalasin (2), along with thirteen known compounds (3–15) were isolated from the wood-decaying fungus Xylaria sp. SWUF08-37. The absolute configurations of 1 were determined by a combination of Marfey’s method and TDDFT ECD calculation and the absolute configurations of 2 were established by TDDFT ECD calculation. Compound 12 showed moderate cytotoxicity against HeLa (IC50?=?19.60?µg/mL), HT29 (IC50?=?17.31?µg/mL), HCT116 (IC50?=?14.28?µg/mL), MCF-7 (IC50?=?15.38?µg/mL), and Vero (IC50?=?24.97?µg/mL) cell lines by MTT assay. Compounds 1 and 2 showed slight cytotoxicity against all tested cancer cell lines. 相似文献
Medicinal plants from Chad grow under special climatic conditions in between the equatorial forest of Central Africa and the desert of North Africa and are understudied. Three medicinal plants from Chad (T. diversifolia, P. Biglobosa and C. Febrifuga) were evaluated for their phenolic composition, antioxidant and enzyme inhibition activities. The total phenolic composition varied from 203.19 ± 0.58 mg GAE/g DW in the ethyl acetate extract of P. biglobosa, to 56.41 ± 0.89 mg GAE/g DW in the methanol extract of C. febrifuga while the total flavonoid content varied from 51.85 ± 0.91 mg QE/g DW in the methanol extract of P. biglobosa to 08.56 ± 0.25 mg QE/g DW in the methanol extract of C. febrifuga. HPLC-DAD revealed that rutin, gallic acid and protocatechuic acid were the most abundant phenolics in T. diversifolia, P. Biglobosa and C. Febrifuga respectively. The antioxidant activity assayed by five different methods revealed very good activity especially in the DPPH?, ABTS?+ and CUPRAC assays where the extracts were more active than the standard compounds used. Good inhibition was exhibited against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with methanol (IC50: 15.63 ± 0.72 µg/mL), ethyl acetate (IC50: 16.20 ± 0.67 µg/mL) extracts of P. biglobosa, and methanol (IC50: 21.53 ± 0.65 µg/mL) and ethyl acetate (IC50: 30.81 ± 0.48 µg/mL) extracts of T. diversifolia showing higher inhibition than galantamine (IC50: 42.20 ± 0.44 µg/mL) against BChE. Equally, good inhibition was shown on α-amylase and α-glucosidase. On the α-glucosidase, the ethyl acetate (IC50 = 12.47 ± 0.61 µg/mL) and methanol extracts (IC50 = 16.51 ± 0.18 µg/mL) of P. biglobosa showed higher activity compared to the standard acarbose (IC50 = 17.35 ± 0.71 µg/mL) and on α-amylase, the ethyl acetate (IC50 = 13.50 ± 0.90 µg/mL) and methanol (IC50 = 18.12 ± 0.33 µg/mL) extracts of P. biglobosa showed higher activity compared to acarbose (IC50 = 23.84 ± 0.25 µg/mL). The results indicate that these plants are good sources of antioxidant phenolics and can be used to manage oxidative stress linked illnesses such as Alzheimer’s disease and diabetes. 相似文献
Poly(amidoamine)s with amino pendant groups were prepared by hydrogen‐transfer polyaddition of primary and secondary amines to bis‐acrylamines. Dansyl cadaverine (DC) doxorubicin (Dox) were bound to the polymers via a cis‐aconityl spacer to give conjugates containing 3 µg of DC per mg of polymer and 28 to 35 µg of Dox per mg of polymer. Release of DC and Dox at physiological and acidic pH varied from 0 to 35% over 48 h and was pH dependent. Although the ISA1Dox conjugate (IC50 = 6 µg Dox · mL?1) presented similar toxicity as the parent polymer without Dox, ISA23Dox showed increased toxicity (IC50 = 10 µg Dox · mL?1). These results suggest that ISA23Dox is able to release biologically active Dox in vitro and that this conjugate might be suitable for further development.
AbstractNovel Mannich base derivatives of glabridin were synthesized and their antiproliferative activity were performed along with our previously reported glabridin-chalcone hybrids molecules (GCHMs) against various human cell lines MDA-MB-231 (breast adenocarcinoma), HEK-293 (embryonic kidney cell line), K562 (leukemia), MCF-7 (breast adenocarcinoma), HeLa (cervix adenocarcinoma), HepG2 (hepatocellular carcinoma) and WRL-68 (hepatic carcinoma). The result showed that the glabridin significantly reduced cell proliferation with IC50 ranges from 3.67 to 58.30?µM against all the tested cell lines. The remarkable reduction in antiproliferative activity 2’,4’-dimethoxyglabridin and GCHMs compounds with phenolic OH groups protected by methoxy (OCH3) groups suggested that the free OH groups are essential factor for the antiproliferative activity of glabridin and its derivatives. The Mannich base derivatives of glabridin showed moderate activity IC50 (2.20–>95.78?µM). Furthermore, in silico target identification analysis revealed that AKT1, DECR1 and NOS1 are the potential targets for glabridin and their derivatives. 相似文献