排序方式: 共有22条查询结果,搜索用时 15 毫秒
1.
Elizaveta D. Gladkova Arina A. Chepanova Ekaterina S. Ilina Alexandra L. Zakharenko Jhannes Reynisson Olga A. Luzina Konstantin P. Volcho Olga I. Lavrik Nariman F. Salakhutdinov 《Molecules (Basel, Switzerland)》2021,26(7)
A new type of berberine derivatives was obtained by the reaction of berberrubine with aliphatic sulfonyl chlorides. The new polycyclic compounds have a sultone ring condensed to C and D rings of a protoberberine core. The reaction conditions were developed to facilitate the formation of sultones with high yields without by-product formation. Thus, it was shown that the order of addition of reagents affects the composition of the reaction products: when sulfochlorides are added to berberrubine, their corresponding 9-O-sulfonates are predominantly formed; when berberrubine is added to pre-generated sulfenes, sultones are the only products. The reaction was shown to proceed stereo-selectively and the cycle configuration was confirmed by 2D NMR spectroscopy. The inhibitory activity of the synthesized sultones and their 12-brominated analogs against the DNA-repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1), an important target for a potential antitumor therapy, was studied. All derivatives were active in the micromolar and submicromolar range, in contrast to the acyclic analogs and 9-O-sulfonates, which were inactive. The significance of the sultone cycle and bromine substituent in binding with the enzyme was confirmed using molecular modeling. The active inhibitors are mostly non-toxic to the HeLa cancer cell line, and several ligands show synergy with topotecan, a topoisomerase 1 poison in clinical use. Thus, novel berberine derivatives can be considered as candidates for adjuvant therapy against cancer. 相似文献
2.
Aldar A. Munkuev Evgenii S. Mozhaitsev Arina A. Chepanova Evgeniy V. Suslov Dina V. Korchagina Olga D. Zakharova Ekaterina S. Ilina Nadezhda S. Dyrkheeva Alexandra L. Zakharenko Jhannes Reynisson Konstantin P. Volcho Nariman F. Salakhutdinov Olga I. Lavrik 《Molecules (Basel, Switzerland)》2021,26(11)
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising target for anticancer therapy due to its ability to counter the effects topoisomerase 1 (Top1) poison, such as topotecan, thus, decreasing their efficacy. Compounds containing adamantane and monoterpenoid residues connected via 1,2,4-triazole or 1,3,4-thiadiazole linkers were synthesized and tested against Tdp1. All the derivatives exhibited inhibition at low micromolar or nanomolar concentrations with the most potent inhibitors having IC50 values in the 0.35–0.57 µM range. The cytotoxicity was determined in the HeLa, HCT-116 and SW837 cancer cell lines; moderate CC50 (µM) values were seen from the mid-teens to no effect at 100 µM. Furthermore, citral derivative 20c, α-pinene-derived compounds 20f, 20g and 25c, and the citronellic acid derivative 25b were found to have a sensitizing effect in conjunction with topotecan in the HeLa cervical cancer and colon adenocarcinoma HCT-116 cell lines. The ligands are predicted to bind in the catalytic pocket of Tdp1 and have favorable physicochemical properties for further development as a potential adjunct therapy with Top1 poisons. 相似文献
3.
Peter Jaein Choi Petr Tomek Moana Tercel Jhannes Reynisson Thomas In Hyeup Park Elizabeth Alexandra Cooper William Alexander Denny Jiney Jose Euphemia Leung 《Molecules (Basel, Switzerland)》2022,27(3)
The CDK4/6 inhibitor palbociclib, combined with endocrine therapy, has been shown to be effective in postmenopausal women with estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer. However, palbociclib is not as effective in the highly aggressive, triple-negative breast cancer that lacks sensitivity to chemotherapy or endocrine therapy. We hypothesized that conjugation of the near-infrared dye MHI-148 with palbociclib can produce a potential theranostic in triple-negative, as well as estrogen receptor-positive, breast cancer cells. In our study, the conjugate was found to have enhanced activity in all mammalian cell lines tested in vitro. However, the conjugate was cytotoxic and did not induce G1 cell cycle arrest in breast cancer cells, suggesting its mechanism of action differs from the parent compound palbociclib. The study highlights the importance of investigating the mechanism of conjugates of near-infrared dyes to therapeutic compounds, as conjugation can potentially result in a change of mechanism or target, with an enhanced cytotoxic effect in this case. 相似文献
4.
Madsen Per Jensen Ole Kiel Amtoft Torben Reynisson Ragnar V. Mikkelsen Jan Hvolgaard Laursen SØren Kolding Troels Emil Larsen Torben Jenner Michael Bohl 《Wireless Personal Communications》2002,23(1):55-66
Unified RF requirements are derived for an UMTS Terrestrial RadioAccess/Frequency Division Duplex (UTRA/FDD) compliant mobile transceiver. Aset of transceiver requirements are proposed with consideration to systemissues including duplex aspects. From these design-compatible requirements areproposed for each functional block in the transceiver. 相似文献
5.
Intercalation of trioxatriangulenium ion in DNA: binding,electron transfer,x-ray crystallography,and electronic structure 总被引:1,自引:0,他引:1
Reynisson J Schuster GB Howerton SB Williams LD Barnett RN Cleveland CL Landman U Harrit N Chaires JB 《Journal of the American Chemical Society》2003,125(8):2072-2083
Trioxatriangulenium ion (TOTA(+)) is a flat, somewhat hydrophobic compound that has a low-energy unoccupied molecular orbital. It binds to duplex DNA by intercalation with a preference for G-C base pairs. Irradiation of intercalated TOTA(+) causes charge (radical cation) injection that results in strand cleavage (after piperidine treatment) primarily at GG steps. The X-ray crystal structure of TOTA(+) intercalated in the hexameric duplex d[CGATCG](2) described here reveals that intercalation of TOTA(+) results in an unusually large extension of the helical rise of the DNA and that the orientation of TOTA(+) is sensitive to hydrogen-bonding interactions with backbone atoms of the DNA. Electronic structure calculations reveal no meaningful charge transfer from DNA to TOTA(+) because the lowest unoccupied molecular orbital of TOTA(+), (LUMO)(T), falls in the gap between the highest occupied molecular orbital, (HOMO)(D), and the (LUMO)(D) of the DNA bases. These calculations reveal the importance of backbone, water, and counterion interactions, which shift the energy levels of the bases and the intercalated TOTA(+) orbitals significantly. The calculations also show that the inserted TOTA(+) strongly polarizes the intercalation cavity where a sheet of excess electron density surrounds the TOTA(+). 相似文献
6.
Muhammad Imadur Rahman Ragnar Reynisson Daniel Figueiredo Ramjee Prasad 《Wireless Personal Communications》2009,50(1):83-97
This article proposes a novel way of grouping users in an orthogonal frequency division multiplexing (OFDM) communication
link based on predefined criteria. The total available spectrum is divided into a number of bands equal to the number of groups.
For efficient time-frequency resource allocation, sub-carrier and band hopping are used simultaneously. Under some constraints,
sub-carriers can also be assigned to different users based on known channel characteristics using dynamic sub-carrier allocation.
Sub-carrier and band hopping are used for mitigating the frequency selectivity of the wireless channel and for minimizing
and avoiding interference in the system. The proposed scheme is equally applicable to both downlink and uplink.
相似文献
Ramjee PrasadEmail: |
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Using Density Functional Theory, the hydrogen bonding energy is calculated for the interaction of phenol and aniline with four model compounds representing the protein backbone and various amino acid site chain residues. The models are methanol, protonated methylamine, formaldehyde and acetate anion. The H-bond energies for the uncharged species are 2.5kcalmol–1, whereas the charged model compounds bind with much higher energies of 20kcalmol–1. The effect of para-substitution on the hydrogen bond energies is determined. Substitution has little effect on the H-bond energy of the neutral complexes (<2kcalmol–1), but for the positively and negatively charged systems substitution drastically alters the binding energies, e.g., 14.3kcalmol–1 for para-NO2. In the context of protein–ligand binding, relatively small changes in binding energy can cause large changes in affinity due to their exponential relationship. This means that for –NO2 an enormous change of 10 orders of magnitude for the affinity constant is predicted. These calculations allow prediction of H-bonds, using different substituents, in order to fine-tune and optimize ligand–protein interactions in the search for drug candidates. 相似文献
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Lisa I. Pilkington Xue Yang Meng‐Wen Liu Yacine Hemar Margaret A. Brimble Jhannes Reynisson 《化学:亚洲杂志》2019,14(8):1117-1127
Several hundred (396) compounds from New Zealand flora with medicinal properties were analyzed for their physicochemical properties. It was found that approximately 10 % fulfilled all the requirements to be considered to be lead‐like, over half of the compounds were deemed to be in the drug‐like space and ≈75 % were in the known drug space. These results indicate the presence of a significant proportion of compounds that are of particular interest to pursue as potential lead compounds or therapeutics. Additionally, compound classes were analyzed separately—most carbonyl‐containing compounds (aldehydes, ketones, esters and lactones), along with phenols were the most lead‐like compounds, which also displayed very good proportions in the drug‐like and known drug space. The information presented herein can be harnessed and utilized in future work, through focussing on the compounds and compound classes that exhibit high‐levels of lead‐likeness for further development. 相似文献