- RNA Control by Photoreversible Acylation
-
External photocontrol over RNA function has emerged as a useful tool for studying nucleic acid biology. Most current methods rely on fully synthetic nucleic acids with photocaged nucleobases, limiting application to relatively short synthetic RNAs. Here we report a method to gain photocontrol over RNA by postsynthetic acylation of 2′-hydroxyls with photoprotecting groups. One-step introduction of these groups efficiently blocks hybridization, which is restored after light exposure. Polyacylation (termed cloaking) enables control over a hammerhead ribozyme, illustrating optical control of RNA catalytic function. Use of the new approach on a transcribed 237 nt RNA aptamer demonstrates the utility of this method to switch on RNA folding in a cellular context, and underlines the potential for application in biological studies.
- Velema, Willem A.,Kietrys, Anna M.,Kool, Eric T.
-
-
Read Online
- Monocarbonyl Analogs of Curcumin based on the pseudopelletierine scaffold: Synthesis and anti-inflammatory activity
-
Curcumin (CUR) is a natural compound that exhibits anti-inflammatory, anti-bacterial, and other biological properties. However, its application as an effective drug is problematic due to its poor oral bioavailability, solubility in water, and poor absorption from the gastrointestinal tract. The aim of this work is to synthesize monocarbonyl analogs of CUR based on the 9-methyl-9-azabicyclo[3.2.1]nonan-3-one (pseudopelletierine, granatanone) scaffold to improve its bioavailability. Granatane is a homologue of tropane, whose structure is present in numerous naturally occurring alkaloids, e.g., l-cocaine and l-scopolamine. In this study, ten new pseudopelletierine-derived monocarbonyl analogs of CUR were successfully synthesized and characterized by spectral methods and X-ray crystallography. Additionally, in vitro test of the cytotoxicity and anti-inflammatory properties of the synthesized compounds were performed.
- Brzezinski, Krzysztof,Eljaszewicz, Andrzej,Gandusekar, Ramesh,Ksiezak, Sylwia,Lazny, Ryszard,Moniuszko, Marcin,Pawelski, Damian,Plonska-Brzezinska, Marta E.,Radziwon, Piotr,Sredzinski, Dariusz,Walewska, Alicja
-
-
- Bronchospasmolytic activity and adenosine receptor binding of some newer 1,3-dipropyl-8-phenyl substituted xanthine derivatives
-
The aldehyde derivatives of 1,3-dipropyl xanthines as described in this paper, constitutes a new series of selective adenosine ligands displaying bronchospasmolytic activity. The effect of substitution at third- and fourth-position of 8-phenyl xanthine ha
- Gumber, Divya,Yadav, Divya,Yadav, Rakesh,Kachler, Sonja,Klotz, Karl Norbert
-
p. 600 - 609
(2020/03/23)
-
- Photoreversible Acylation Reagents
-
Reagents and methods to cloak and uncloak RNA polymers and applications thereof are provided. Photocloaking molecules are used to label RNA polymers. Radiant energy is used to remove photoreleaseable protecting adducts and revert a RNA polymer to its nati
- -
-
Paragraph 0218-0221
(2019/09/06)
-
- With tyrosine kinase inhibitory activity of 2 - indolone derivatives and its preparation method and application
-
The invention discloses a 2-indolone derivative with tyrosine kinase inhibition activity, geometric isomers and medicinal salts thereof, and a preparation method and an application of the above compounds. Tyrosine kinase inhibition activity evaluation confirms that the derivative is a compound with good tyrosine kinase activity, so the derivative has potential antitumor activity, and can be used to prepare tumor disease prevention and treatment medicines (antitumor medicines) as an active component. The derivative provides research and enforcement foundation for tumor treatment, and has a wide application prospect.
- -
-
-
- Synthesis and Evaluation of a New Series of 8-(2-Nitroaryl)Xanthines as Adenosine Receptor Ligands
-
(Table presented.). A new series of 1,3-dimethylxanthine derivatives bearing 8-(2-nitroaryl) residue was synthesized and evaluated for affinity for recombinant human adenosine receptors subtypes. Nitrate esters of 7-substituted-1,3-dimethyl-8-phenylxanthines were also synthesized and tested. Introducing a nitro substituent at the 2-position of the 8-substituted phenyl ring resulted in generally low affinity for adenosine receptors (ARs), selectivity toward the A2A subtype was enhanced in some of the compounds. 8-(4-Cyclopentyloxy-5-methoxy-2-nitrophenyl)-1,3-dimethylxanthine (9e) proved to be a potent compound among the 2-nitrophenyl substituted xanthines exhibiting a Ki = 1 μM at human A2A ARs with at least 30 fold selectivity versus human A1 and A2B ARs. Replacement of 8-chloropropoxy phenyl with 8-nitrooxypropoxy phenyl resulted in a negligible change in binding affinity of the 8-substituted xanthines for various AR subtypes. Drug Dev Res 77 : 241–250, 2016.
- Bansal, Ranju,Kumar, Gulshan,Rohilla, Suman,Klotz, Karl-Norbert,Kachler, Sonja,Young, Louise C.,Harvey, Alan L.
-
p. 241 - 250
(2016/08/28)
-
- TRICYCLIC PIPERIDINE COMPOUNDS
-
The present invention relates to compounds of the formula (I) wherein R1a, R1b, R2, R3, (R4)n and ring (A) are as described in the description, to their preparation, to pharmaceutically acc
- -
-
Page/Page column 77
(2016/11/21)
-
- Indolinone based LRRK2 kinase inhibitors with a key hydrogen bond
-
The most prevalent leucine-rich repeat kinase 2 (LRRK2) mutation G2019S is associated with Parkinson's disease (PD). It enhances kinase activity and has been identified in both familial and sporadic cases. Kinase activity was reported to be required for LRRK2 mutants to exert their toxic effects. Hence LRRK2 kinase inhibition may be a promising therapeutic target for PD. Here we report on the discovery and characterization of indolinone based LRRK2 inhibitors. Indolinone 15b, the most potent and selective inhibitor of the present series, is characterized by an IC50of 15 nM against wild-type LRRK2 and 10 nM against the LRRK2 G2019S mutant, respectively. Compound 15b was further evaluated in a kinase panel including 46 human protein kinases and in a zebrafish embryo phenotype assay, which enabled toxicity determination in whole organisms.
- G?ring, Stefan,Taymans, Jean-Marc,Baekelandt, Veerle,Schmidt, Boris
-
p. 4630 - 4637
(2015/02/05)
-
- Synthesis, antimalarial activity and cytotoxic potential of new monocarbonyl analogues of curcumin
-
A series of novel monocarbonyl analogues of curcumin have been designed, synthesized and tested for their activity against Molt4, HeLa, PC3, DU145 and KB cancer cell lines. Six of the analogues showed potent cytotoxicity towards these cell lines with IC50 values below 1 μM, which is better than doxorubicin, a US FDA approved drug. Several analogues were also found to be active against both CQ-resistant (W2 clone) and CQ-sensitive (D6) strains of Plasmodium falciparum in an in-vitro antimalarial screening. This level of activity warrants further investigation of the compounds for development as anticancer and antimalarial agents.
- Manohar, Sunny,Khan, Shabana I.,Kandi, Shamseer Kulangara,Raj, Kranthi,Sun, Guojing,Yang, Xiaochuan,Calderon Molina, Angie D.,Ni, Nanting,Wang, Binghe,Rawat, Diwan S.
-
p. 112 - 116
(2013/02/23)
-
- Modification of a promiscuous inhibitor shifts the inhibition from γ-secretase to FLT-3
-
The inhibition of FLT-3 activity is an interesting target for the treatment of acute myeloid leukemia (AML). The serendipitous identification of FLT-3 inhibitors from a CK1/γ-secretase programme provided compounds with dual inhibitory activity. We analyzed the structure-activity relationship of these inhibitors and derivatized them to arrive at compounds with reduced impact on γ-secretase activity and enhanced FLT-3 inhibition.
- Amombo, Ghislaine Marlyse Okala,Kramer, Thomas,Lo Monte, Fabio,Goering, Stefan,Fach, Matthias,Smith, Steven,Kolb, Stephanie,Schubenel, Robert,Baumann, Karlheinz,Schmidt, Boris
-
supporting information
p. 7634 - 7640
(2013/02/21)
-
- Synthesis of some imidazolyl-substituted 2-benzylidene indanone derivatives as potent aromatase inhibitors for breast cancer therapy
-
The synthesis and aromatase inhibitory activity of a new series of 2-benzylidene indanones is presented. The imidazolyl-substituted indanones displayed potent aromatase inhibitory activity. The vanilloid-based derivative 2-[4-(3-imidazol-1-ylpropoxy)-3-me
- Bansal, Ranju,Narang, Gaurav,Zimmer, Christina,Hartmann, Rolf W.
-
experimental part
p. 661 - 669
(2012/05/20)
-
- Synthesis and QSAR studies of 16-(3 -methoxy-4-substituted benzylidene) androstene derivatives as anticancer agents
-
In a systematic effort aimed at identifying new steroidal cytotoxic agents with potent antipoliferative activity against cancer cells and developing their QSAR models, a series of 16-(3- methoxy-4-substituted benzylidene)androst-5-ene derivatives have been synthesized. The selected compounds are evaluated for antineoplastic activity against a panel of three human cell lines- breast, CNS and lungs at NCI, Bethesda, USA. The results presented herein indicate that compound 15-18, 21, 22, 25-30 are active anticancer agents. The QSAR investigation with multiple linear regression analysis has been applied to find a correlation between different calculated physicochemical parameters of these compounds and biological activity. Application of datasets by using CODESSA software has led to QSAR equations based on the 3 descriptors. The significant QSAR models have been obtained with R2 values which range from 0.9692-0.8225 and good predictive performance (q2 range: 0.9264-0.7121). These models are expected to be useful for the anticancer screening of androstene derivatives having substitution at position 3, 16 and 17 of steroid nucleus.
- Dubey, Sonal,Kaur, Parmeet,Jindal, Dharam Paul,Satyanarayan, Yalamanchili Darji,Piplani, Poonam
-
scheme or table
p. 948 - 955
(2010/10/18)
-
- Synthesis of a series of 8-(substituted-phenyl)xanthines and a study on the effects of substitution pattern of phenyl substituents on affinity for adenosine A1 and A2A receptors
-
A new series of 8-(substituted-phenyl)xanthines have been synthesized and compounds were evaluated for their affinity for A1 and A2 adenosine receptors (AR) using radioligand binding assays. The effects of varying the positions of 8-phenyl substituents on affinity and selectivity at A1 and A2A adenosine receptors have been studied. Isovanilloid 1,3-dimethyl-8-[4-methoxy-3-(2-morpholin-4-ylethoxy)phenylxanthine (9d) displayed the highest affinity and selectivity towards A2A AR subtypes with Ki = 100 nM over A1 receptors (Ki > 100 mM). It has been observed that substitution pattern on 8-phenyl group greatly affects the affinity and selectivity at adenosine receptors, with A2A tolerating bulkier substituents than did A1 receptors.
- Bansal, Ranju,Kumar, Gulshan,Gandhi, Deepika,Young, Louise C.,Harvey, Alan L.
-
experimental part
p. 2122 - 2127
(2009/09/30)
-
- Synthesis and antimicrobial activity of novel analogs of trifenagrel
-
Novel analogs of trifenagrel were synthesized by using inexpensive and reusable phosphotungstic acid, H3[PW12O40] (3 mol %) catalyst under classical heating. Two of the newly synthesized triaryl imidazoles exhibited moderate antibacterial activity.
- Nagarapu, Lingaiah,Aneesa,Satyender, Apuri,Chandana,Bantu, Rajaskaker
-
experimental part
p. 195 - 200
(2009/07/19)
-