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1.
Abstract

1-Carbonyl 5-fluorouracil derivatives,5′-acyl-5-fluorouridines, and 5-fluorouridilic acid esters were synthesized and their antitumor activities were tested.  相似文献   

2.
Chao Gao  Dai  Honglin  Si  Xiaojie  Zhang  Yutong  Liu  Limin  Wang  Zhengjie  Meng  Yaqi  Zhang  Yang  Wang  Tao  Zheng  Jiaxin  Shan  Lihong  Liu  Hongmin  Zhang  Qiurong 《Russian Journal of Bioorganic Chemistry》2022,48(2):411-422
Russian Journal of Bioorganic Chemistry - In order to discover novel high efficiency and low toxic anticancer drugs, a series of novel 2-amino-5-ethylpyrimidine derivatives (XIIa–x) were...  相似文献   

3.
Abstract

5-Ethynyl-1-(2-deoxy-β-D-ribofuranosyl)imidazole-4-carbonitrile (4) and -carboxamide (5) and 5-ethynyl-1-(5-deoxy-β-D-ribofuranosyl)imidazole-4-carbonitrile (11) and -carboxamide (12) have been synthesized from the corresponding 5-iodo derivatives 2 and 7 by a palladium-catalyzed cross-coupling reaction with (tri-methylsilyl)acetylene. The aglycons, 5-ethynylimidazole derivatives 14 and 15 were synthesized by the hydrolytic cleavage of the corresponding nucleosides. The antileukemic activity of these nucleosides and base analogues are also described.  相似文献   

4.
The formation of (4R)-4-carbamoyl-4-[(4R)-3-O-benzyl-1,2-O-isopropylidene-β-l-threofuranos-4-C-yl]-oxazolidin-2-one instead of expected imidazolidin-2,4-dione (hydantoin) derivative from 5-amino-5-cyano-5-deoxy-3-O-benzyl-1,2-O-isopropylidene-α-d-glucofuranose or 3-O-benzyl-1,2-O-isopropylidene-α-d-xylo-hexofuranos-5-ulose under Bucherer-Bergs reaction conditions is reported. Single crystal X-ray diffraction data revealed that 3T4 is the prefered conformation for the furanose ring, while E2 and 2T1 conformations are adopted by the 1,3-dioxolane and 2-oxazolidinone five-membered rings, respectively.  相似文献   

5.
This article deals with the synthesis of 4-(2-hydroxyquinolin-3-yl)-6-phenyl-5,6-dihydropyrimidin derivatives (2a–f), on condensation with various aromatic aldehydes and ketones in aqueous ethanolic NaOH solution yielding the corresponding chalcones (3). These chalcones were further reacted with thiourea/urea in the presence of a base, which led to the formation of the titled derivatives (2a–f). The newly synthesized heterocyles were characterized by elemental analysis, FTIR, 1HNMR, and electronic and mass spectral data. The compounds (2a and 2b) were evulated for in vitro cyctotoxicity against human breast adenocarcinoma cell (MCF-7). In MTT cytotoxicity studies, both quinolinde derivatives were found most effective. The binding interaction behavior of the compound (2a) and (2d) with calf thymus-DNA (CT-DNA) was studied by electronic spectra, viscosity measurements, and thermal denaturation studies. On binding to CT-DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. The binding constant (Kb) observed 4.3 × 105 M?1 for (2a), and 3.8 × 105 M?1 for (2d) suggested that compound (2a) binds more strongly with base pairs than (2d).  相似文献   

6.
The syntheses of the ribo- and deoxyribonucleoside derivatives of 4-formyl-4-imidazolin-2-one, isosteric isomers of uridine and 2'-deoxyuridine, respectively, were carried out by ring contraction of the corresponding 5-bromouracil nucleosides, followed by conversion of the carboxyl side-chain of the products to the respective carboxaldehyde derivatives.  相似文献   

7.
Abstract

The introduction of sulfonamido group on the C-2 position of pyrimidine nucleosides was achieved by ring opening of 2,2′- and 2,3′-anhydronucleosides. N-sulfonyl derivatives of nucleobases and sulfonamido derivatives of nucleosides were assayed for in vitro antitumor activity.  相似文献   

8.
A series of new sulfonamides have been synthesized from Ampyrone with different benzene sulfonyl chlorides to yield the N-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) benzenesulfonamides (4ae). All synthesized compounds were characterized on the basis of FTIR, 1H NMR, and 13C NMR, and also by the aid of mass spectral data. Further, all synthesized compounds have studied for their in vitro antimicrobial activities against selected bacterial as well as fungal strains by the agar well diffusion method. Free radical scavenging activity has been investigated by using DPPH method. Among all the synthesized compounds, 4b, 4d, and 4e exhibited significant antimicrobial and antioxidant activities.  相似文献   

9.
A method for the convenient synthesis of the recently isolated allylic gonadal steroids, 3 alpha-hydroxy-4-pregnen-20-one (3 alpha-dihydroprogesterone; 3 alpha-DHP) and 3 alpha-hydroxy-4-androsten-17-one (3 alpha-HA), was developed using 4-pregnene-3,20-dione (progesterone) and 4-androstene-3,17-dione as substrates and potassium trisiamylborohydride (KS-Selectride) as reducing agent. Similar reactions were also used for the reduction of 5 alpha-pregnane-3,20-dione to 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-HP). The yields were about 15%, 50%, and greater than 90% for 3 alpha-DHP, 3 alpha-HA and 3 alpha-HP, respectively. Structures of the products, including the 3 beta-isomers and the 17 alpha-epimer, formed in these reactions were determined by NMR and mass spectroscopic methods.  相似文献   

10.
Betulin (lup-20(29)-ene-3β, 28-diol) is a naturally occurring triterpene, which is found in substantial amounts from the outer bark of birch trees. A library of 51 structurally diverse semisynthetic betulin derivatives was screened against five bacterial strains, Enterobacter aerogenes, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus and a fungal strain Candida albicans, using broth microdilution assays. Primary antimicrobial screening at 50 µM concentration led to the identification of five compounds showing antimicrobial properties (inhibition of growth by >70% against one or more microbial strains). According to the dose-response results, 28-O-(N-acetylanthraniloyl)betulin (compound 5) was the most active, showing MIC90 of 6.25 µM against two Gram-positive bacteria, E. faecalis and S. aureus. However, the activity of this compound was affected by albumin binding, which was demonstrated by the loss of activity in a host-pathogen co-culture assay as well as in the antibacterial assay in the presence of increased concentration of albumin. Furthermore, the effects on mammalian cells were evaluated by cytotoxicity assessment on hepatocyte cell culture after 24 h exposure to the compounds. Betulinic aldehyde (18), betulin-28-oxime (31) and hetero cycloadduct with acetoxy groups at carbon atoms 3 and 28 and ethyl substituent at the triazolo ring (43) displayed cytotoxicity towards hepatocytes, with IC50 values of 47, 25 and 16 µM, respectively. The IC50 value for 28-O-(N-acetylanthraniloyl)betulin (5) was 56 µM. The current study presents an insight into using betulin scaffold for developing derivatives with antibacterial potential, and furthermore the necessity of in-depth analysis of found actives through selectivity profiling and follow-up studies including in silico ADMET predictions.  相似文献   

11.
Liu Limin  Zhengjie  Wang  Xiujuan  Liu  Chao  Gao  Honglin  Dai  Tao  Wang  Na  Li  Heyi  Yan  Yang  Zhang  Luye  Zhang  Jiaxin  Zheng  Lihong  Shan  Hongmin  Liu  Qiurong  Zhang 《Russian Journal of Bioorganic Chemistry》2021,47(6):1301-1311
Russian Journal of Bioorganic Chemistry - In order to find efficient new antitumor drugs, a series of novel pyrimidine derivatives containing urea moiety were designed and synthesized, and the...  相似文献   

12.
Abstract

Simple method for the preparation of anhydrides of nucleoside-5′-monophosphoric acid and with 1-hydroxyethane-1,1-diylbis(phosphonic acid) has been developed.  相似文献   

13.
Arthropod-borne flavivirus infection continues to cause significant morbidity and mortality worldwide. Identification of drug targets and novel antiflaviviral compounds to treat these diseases has become a global health imperative. A previous screen of 235,456 commercially available small molecules identified the 2-thioxothiazolidin-4-one family of compounds as inhibitors of the flaviviral NS5 capping enzyme, a promising target for antiviral drug development. Rational drug design methodologies enabled identification of lead compound BG-323 from this series. We have shown previously that BG-323 potently inhibits NS5 capping enzyme activity, displays antiviral effects in dengue virus replicon assays and inhibits growth of West Nile and yellow fever viruses with low cytotoxicity in vitro. In this study we further characterized BG-323’s antiviral activity in vitro and in vivo. We found that BG-323 was able to reduce replication of WNV (NY99) and Powassan viruses in culture, and we were unable to force resistance into WNV (Kunjin) in long-term culture experiments. We then evaluated the antiviral activity of BG-323 in a murine model. Mice were challenged with WNV NY99 and administered BG-323 or mock by IP inoculation immediately post challenge and twice daily thereafter. Mice were bled and viremia was quantified on day three. No significant differences in viremia were observed between BG-323-treated and control groups and clinical scores indicated both BG-323-treated and control mice developed signs of illness on approximately the same day post challenge. To determine whether differences in in vitro and in vivo efficacy were due to unfavorable pharmacokinetic properties of BG-323, we conducted a pharmacokinetic evaluation of this small molecule. Insights from pharmacokinetic studies indicate that BG-323 is cell permeable, has a low efflux ratio and does not significantly inhibit two common cytochrome P450 (CYP P450) isoforms thus suggesting this molecule may be less likely to cause adverse drug interactions. However, the T1/2 of BG-323 was suboptimal and the percent of drug bound to plasma binding proteins was high. Future studies with BG-323 will be aimed at increasing the T1/2 and determining strategies for mitigating the effects of high plasma protein binding, which likely contribute to low in vivo efficacy.  相似文献   

14.
15.
Russian Journal of Bioorganic Chemistry - In this study, a series of new N4-alkyl-N2-phenyl-pyrrolo[3,2-d]pyrimidine-2,4-diamine derivatives has been designed and synthesized. The...  相似文献   

16.
New cyclopropane derivatives of betulin were synthesized by attachment of dichlorocarbenes or dibromocarbenes to the double bond of betulin diacetate, followed by the deprotection of hydroxyl groups. The betulin cyclopropane derivative was obtained from 20,29-dihydro-20,29-dichloromethylenebetulin by treatment with lithium in tert-butanol. These compounds were converted into the corresponding derivatives of betulonic acid by oxidation with chromium trioxide. The reduction of oxo group with sodium borohydride led to the corresponding derivatives of betulinic acid. 20,29-Dihydro-20,29-dichloromethylenebetulinic acid proved to be the most cytotoxic toward human melanoma of the Colo 38 and Bro lines and human ovarian carcinoma of the CaOv line (IC50 10 μM). 20,29-Dihydro-20,29-dibromomethylenebetulinic acid inhibited the growth of the Bro melanoma cell line and the CaOv carcinoma cell line practically by 50% at a concentration of 10 μM. The other derivatives of betulinic and betulonic acids were active toward all of the three cancer cell lines at concentrations higher than 10 μM.__________Translated from Bioorganicheskaya Khimiya, Vol. 31, No. 3, 2005, pp. 320–325.Original Russian Text Copyright © 2005 by Symon, Veselova, Kaplun, Vlasenkova, Fedorova, Lyutik, Gerasimova, Shvets.  相似文献   

17.
New 2-phenacyl-1,2,4-triazol-3-ones were obtained by the reaction of 5-alkyl-1,2,4-triazol-3-ones with α-bromoacetophenone in an alkaline medium. Selective reduction of the side chain carbonyl group to hydroxy group was achieved with NaBH4. The reaction of some compounds containing a phenolic hydroxyl with 4-toluenesulfonyl chloride or benzyl bromide in the presence of NaOH led to tosylated or benzylated derivatives. The tosylation or benzylation at the alcoholic hydroxyl was carried out in the presence of sodium metal. Some of the newly synthesized compounds revealed an antimicrobial activity; 6 of 14 new compounds that were studied by the National Cancer Institute were found to possess antitumor activity.__________Translated from Bioorganicheskaya Khimiya, Vol. 31, No. 4, 2005, pp. 430–440.Original Russian Text Copyright ¢ 2005 by N. Demirbas, A. Demirbas, Karaoglu.The text was submitted by the authors in English.  相似文献   

18.
Russian Journal of Bioorganic Chemistry - To obtain nucleoside derivatives with antibacterial activity, we have proposed three ways of the synthesis of 5-alkylthiomethyl-2'-deoxyuridines, which...  相似文献   

19.
Russian Journal of Bioorganic Chemistry - A series of diterpenes that contain the morpholine, pyrrolidine, benzyl, nitrophenyl, and 1,2,3-tetrazole heterocyclic fragments have been synthesized from...  相似文献   

20.
Russian Journal of Bioorganic Chemistry - Phase transfer catalysis reaction of 4-hydroxy-6-methyl-2H-chromen-2-one with alkyl halides afforded C4 oxygen alkylation products of 2H-chromen-2-one...  相似文献   

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