Abstract:
:Among the plant constituents of Clerodendrum colebrookianum Walp., acteoside, martinoside, and osmanthuside β6 interact with ROCK, a drug target for cancer. In this study, aglycone fragments of these plant constituents (caffeic acid, ferulic acid, and p-coumaric acid) along with the homopiperazine ring of fasudil (standard ROCK inhibitor) were used to design hybrid molecules. The designed molecules interact with the key hinge region residue Met156/Met157 of ROCK I/II in a stable manner according to our docking and molecular dynamics simulations. These compounds were synthesized and tested in vitro in SW480, MDA-MB-231, and A-549 cancer cell lines. The most promising compound was chemically optimized to obtain a thiourea analog, 6a (IC50 = 25 µM), which has >3-fold higher antiproliferative activity than fasudil (IC50 = 87 µM) in SW480 cells. Treatment with this molecule also inhibits the migration of colon cancer cells and induces cell apoptosis. Further, SPR experiments suggests that the binding affinity of 6a with ROCK I protein is better than that of fasudil. Hence, the drug-like natural product analog 6a constitutes a highly promising new anticancer lead.Communicated by Ramaswamy H. Sarma.
journal_name
J Biomol Struct Dynjournal_title
Journal of biomolecular structure & dynamicsauthors
Arya H,Yadav CS,Lin SY,Syed SB,Charles MRC,Kannadasan S,Hsieh HP,Singh SS,Gajurel PR,Coumar MSdoi
10.1080/07391102.2019.1664326subject
Has Abstractpub_date
2020-08-01 00:00:00pages
3563-3577issue
12eissn
0739-1102issn
1538-0254journal_volume
38pub_type
杂志文章abstract::A mononuclear cadmium(II) complex of formula [Cd(5,5'-dmbipy)2(OAc)2]·2H2O (5,5'-dmbipy = 5,5'-dimethyl-2,2'-bipyridine and OAc = acetato ligand) has been synthesized and characterized by FT-IR, UV-Vis, 1H-NMR, elemental analysis and single-crystal X-ray structure analysis. The molecular structure of the complex shows...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2019.1570867
更新日期:2020-01-01 00:00:00
abstract::At high binding densities acridine orange (AO) forms complexes with ds DNA which are insoluble in aqueous media. These complexes are characterized by high red- and minimal green-luminescence, 1:1 (dye/P) stoichiometry and resemble complexes of AO with ss nucleic acids. Formation of these complexes can be conveniently ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1984.10507532
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abstract::We studied the Tetrahymena thermophila rRNA IVS sequence with the aim of obtaining a model of the structure characterized by the bases proximity of the self-reactions sites. The considered sequence kept up those fragments essential for its catalytic activity as demonstrated by deletion mutants. The first step was the ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1991.10507864
更新日期:1991-04-01 00:00:00
abstract::Crystals of the small ribosomal subunit from Thermus thermophilus diffract to 3A and exhibit reasonable isomorphism and moderate resistance to irradiation. A 5A MIR map of this particle shows a similar shape to the part assigned to this particle within the cryo-EM reconstructions of the whole ribosome and contains reg...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2000.10506553
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abstract::The binding of quinolones, nalidixic acid (Nal), oxolinic acid (Oxo) with double stranded polynucleotides was undertaken by using UV-melting, UV-Vis absorption, fluorescence and CD spectroscopic techniques. The binding of Nal or Oxo to the polynucleotides under low-salt buffer conditions were determined for poly (dA)....
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2002.10506844
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abstract::Seven new quinoline-based bioorganic compounds were prepared by solvent-free synthesis and characterized using spectral techniques. The binding of these compounds with human serum albumin (HSA) was investigated by multi-spectroscopic methods. The quenching of Trp fluorescence upon addition of these compounds to HSA co...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1496141
更新日期:2019-07-01 00:00:00
abstract::The location, orientation and dynamics of a thiazole-containing analogue of distamycin 1 bound to the decadeoxyribonucleotide d-[CGCAATTGCG]2 have been studied by non-exchangable and imino proton NMR resonances of the 1:1 complex. Using NOE difference, COSY and NOESY experiments, lexitropsin (1) was located in the min...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1991.10507890
更新日期:1991-08-01 00:00:00
abstract::Chlamydia trachomatis (C.t) is a Gram-negative obligate intracellular bacteria and is a major causative of infectious blindness and sexually transmitted diseases. Among the varied serovars of this organism, A, B and C are reported as prominent ocular pathogens. Genomic studies of these strains shall aid in deciphering...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2017.1343685
更新日期:2018-06-01 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
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doi:10.1080/07391102.2009.10507304
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2013.819789
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abstract::COVID-19 is a novel severe acute respiratory syndrome coronavirus. Currently, there is no effective treatment and vaccines seem to be the solution in the future. Virtual screening of potential drugs against the S protein of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) has provided small molecular comp...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1837676
更新日期:2020-10-29 00:00:00
abstract::The NIa protease of Potyviridae is the major viral protease that processes potyviral polyproteins. The NIa protease coding region of Cardamom mosaic virus (CdMV) is amplified from the viral cDNA, cloned and expressed in Escherichia coli. NIa protease forms inclusion bodies in E.coli. The inclusion bodies are solubiliz...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2012.706078
更新日期:2013-01-01 00:00:00
abstract::Communicated by Ramaswamy H. Sarma. ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1507839
更新日期:2019-08-01 00:00:00
abstract::The World Health Organization has classified the COVID-19 outbreak a pandemic which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and declared it a global health emergency. Repurposing drugs with minimum side effects are one approach to quickly respond in attempt to prevent the spread of CO...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1863265
更新日期:2020-12-27 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1867640
更新日期:2021-01-05 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2001.10506736
更新日期:2001-10-01 00:00:00
abstract::The interaction of Δ- and Λ-[Ru(phen)2DPPZ]2+ (DPPZ = dipyrido[3,2-a:2', 3'-c]phenazine, phen = phenanthroline) with a G-quadruplex formed from 5'-G2T2G2TGTG2T2G2-3'(15-mer) was investigated. The well-known enhancement of luminescence intensity (the 'light-switch' effect) was observed for the [Ru(phen)2DPPZ]2+ complex...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2017.1345324
更新日期:2018-06-01 00:00:00
abstract::The purpose of this study was to investigate the site-selective binding of erlotinib hydrochloride (ET), a targeted anticancer drug, to bovine serum albumin (BSA) through 1H NMR, spectroscopic, thermodynamic, and molecular modeling methods. The fluorescence quenching of BSA by ET was a result of the formation of BSA-E...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2012.726532
更新日期:2013-10-01 00:00:00
abstract::P-glycoprotein (P-gp) is a main factor contributing to multidrug resistance. The effect of this transporter protein on limiting the effectiveness of chemotherapy has been shown by various studies. In a previous report, we synthesized some 14-dihydropyridine (DHP) derivatives as inhibitors of human P-gp. In the present...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2016.1268976
更新日期:2018-01-01 00:00:00
abstract::In the past two decades RNase A has been the focus of diverse investigations in order to understand the nature of substrate binding and to know the mechanism of enzyme action. Although this system is reasonably well characterized from the view point of some of the binding sites, the details of interactions in the seco...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1994.10508761
更新日期:1994-12-01 00:00:00
abstract::Partition ratios of 8 free l-amino acids (Gln, Glu, His, Lys, Met, Ser, Thr, and Tyr) were measured in 10 different polymer/polymer aqueous two-phase systems containing 0.15 M NaCl in 0.01 M phosphate buffer, pH 7.4. The solute-specific coefficients representing the solute dipole/dipole, hydrogen-bonding and electrost...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2013.800994
更新日期:2014-01-01 00:00:00
abstract::Novel [Pd(o-CH2C6H4P(o-tolyl)2)(histidine)] (1) and [Pd(o-CH2C6H4P(o tolyl)2)(phenylalanine)] (2) P,C-orthopalladated complexes have been prepared and characterized by elemental analysis, IR and NMR spectroscopy. To study the stability of the compounds in biological media, the complexes were incubated in Tris buffer d...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1865202
更新日期:2020-12-24 00:00:00
abstract::We performed molecular dynamics simulations for various oligomers with different beta-sheet conformations consisting of alpha-Synuclein 71-82 residues using an all atom force field and explicit water model. Tetramers of antiparallel beta-sheet are shown to be stable, whereas parallel sheets are highly unstable due to ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2009.10507314
更新日期:2009-12-01 00:00:00
abstract::The concept of "words" in continuous languages devoid of blanks is introduced and an operational definition of words given. With this novel concept nucleotide sequences become object for linguistic analysis. The typical word size of the nucleotide language is found to be 3 to 5 (tri- to pentamers). Different genomes h...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1986.10507643
更新日期:1986-08-01 00:00:00
abstract::Transcription factor NAM-B1 has a major role in the process of senescence, which results in higher Fe and Zn concentrations in grains of wild wheat (T. durum; Td). The absence of the wild type NAMB1 in T. aestivum (Ta), one of the cardinal crops essential for more than 1/3rd of the global population, affects Fe and Zn...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2019.1680435
更新日期:2020-08-01 00:00:00
abstract::The hexachlorocyclotriphosphaze compound (N3P3Cl6, HCCP) was reacted with excess (E)-(1-(4'-oxyphenyl)-3-(substituted-phenyl)prop-2-en-1-ones (2-11) to produce hexakis[(1-(4-oxyphenyl)-3-(substituted-phenyl)prop-2-en-1-one)]cyclotriphosphazenes (CP 2-11). The structures of products (CP 2-11) were confirmed using eleme...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1846621
更新日期:2020-11-19 00:00:00
abstract::A new molecular mechanism of trinucleotide expansion diseases is suggested. The mechanism involves the formation of double-helical RNA hairpins by transcripts carrying (CNG)(n) sequences, which are processed via the RNAi pathway with subsequent RNA silencing of genes containing (CNG)(n) sequences. Depletion of protein...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2005.10531230
更新日期:2005-12-01 00:00:00
abstract::Fpg protein (formamidopyrimidine or 8-oxoguanine DNA glycosylase) from E. coli catalyzes excision of several damaged purine bases, including 8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine from DNA. In this study the interaction of E. coli Fpg with various specific and nonspecific oligodeoxynucleo...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1999.10508363
更新日期:1999-10-01 00:00:00
abstract::EcoRII DNA methyltransferase (M.EcoRII) recognizes the DNA sequence 5'.CC*T/AGG.3' and catalyzes the transfer of the methyl group from S-adenosyl-L-methionine to the C5 position of the inner cytosine residue (C*). We obtained several DNA duplexes containing photoactive 5-iodo-2'-deoxyuridine (i(5)dU) or 5-[4-(3-(trifl...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2002.10506860
更新日期:2002-12-01 00:00:00
abstract::The structural analysis of the photoactivated binary system of complementary-addressing nucleic acid sequences (1:2:3) by high-resolution NMR spectroscopy and restrained molecular dynamics is reported. The binary system comprised a 12 base-pair target DNA sequence, pdGTATCAGTTTCT (1), and two hexanucleotides, (dAGAAAC...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1999.10508353
更新日期:1999-10-01 00:00:00