MyMedR

Molecular Basis of Modulating Adenosine Receptors Activities

Mahmod Al-Qattan MN, Mordi MN

Curr Pharm Des, 2019;25(7):817-831.

PMID: 30834826 DOI: 10.2174/1381612825666190304122624

Modulating cellular processes through extracellular chemical stimuli is medicinally an attractive approach to control disease conditions. GPCRs are the most important group of transmembranal receptors that produce different patterns of activations using intracellular mediators (such as G-proteins and Beta-arrestins). Adenosine receptors (ARs) belong to GPCR class and are divided into A1AR, A2AAR, A2BAR and A3AR. ARs control different physiological activities thus considered valuable target to control neural, heart, inflammatory and other metabolic disorders. Targeting ARs using small molecules essentially works by binding orthosteric and/or allosteric sites of the receptors. Although targeting orthosteric site is considered typical to modulate receptor activity, allosteric sites provide better subtype selectivity, saturable modulation of activity and variable activation patterns. Each receptor exists in dynamical equilibrium between conformational ensembles. The equilibrium is affected by receptor interaction with other molecules. Changing the population of conformational ensembles of the receptor is the method by which orthosteric, allosteric and other cellular components control receptor signaling. Herein, the interactions of ARs with orthosteric, allosteric ligands as well as intracellular mediators are described. A quinary interaction model for the receptor is proposed and energy wells for major conformational ensembles are retrieved.

Matched MeSH terms: Ligands

Fulltext Polymer Ligands Derived from Jute Fiber for Heavy Metal Removal from Electroplating Wastewater

Rahman ML, Fui CJ, Ting TX, Sarjadi MS, Arshad SE, Musta B

Polymers (Basel), 2020 Oct 29;12(11).

PMID: 33137923 DOI: 10.3390/polym12112521

Industrial operations, domestic and agricultural activities worldwide have had major problems with various contaminants caused by environmental pollution. Heavy metal pollution in wastewater also a prominent issue; therefore, a well built and economical treatment technology is demanded for pollution-free wastewater. The present work emphasized pure cellulose extracted from jute fiber and further modification was performed by a free radical grafting reaction, which resulted in poly(methyl acrylate) (PMA)-grafted cellulose and poly(acrylonitrile)-grafted cellulose. Subsequently, poly(hydroxamic acid) and poly(amidoxime) ligands were prepared from the PMA-grafted cellulose and PAN-grafted cellulose, respectively. An adsorption study was performed using the desired ligands with heavy metals such as copper, cobalt, chromium and nickel ions. The binding capacity (qe) with copper ions for poly(hydroxamic acid) is 352 mg g-1 whereas qe for poly(amidoxime) ligand it was exhibited as 310 mg g-1. Other metal ions (chromium, cobalt and nickel) show significance binding properties at pH 6. The Langmuir and Freundlich isotherm study was also performed. The Freundlich isotherm model showed good correlation coefficients for all metal ions, indicating that multiple-layers adsorption was occurred by the polymer ligands. The reusability was evaluated and the adsorbents can be reused for 7 cycles without significant loss of removal performance. Both ligands showed outstanding metals removal capacity from the industrial wastewater as such 98% of copper can be removed from electroplating wastewater and other metals (cobalt, chromium, nickel and lead) can also be removed up to 90%.

Matched MeSH terms: Ligands

Ajmalicine and its Analogues Against AChE and BuChE for the Management of Alzheimer's Disease: An In-silico Study

Liu S, Dang M, Lei Y, Ahmad SS, Khalid M, Kamal MA, et al.

Curr Pharm Des, 2020;26(37):4808-4814.

PMID: 32264807 DOI: 10.2174/1381612826666200407161842

BACKGROUND: Alzheimer's disease (AD) is the most well-known reason for disability in persons aged greater than 65 years worldwide. AD influences the part of the brain that controls cognitive and non-cognitive functions.

OBJECTIVE: The study focuses on the screening of natural compounds for the inhibition of AChE and BuChE using a computational methodology.

METHODS: We performed a docking-based virtual screening utilizing the 3D structure of AChE and BuChE to search for potential inhibitors for AD. In this work, a screened inhibitor Ajmalicine similarity search was carried out against a natural products database (Super Natural II). Lipinski rule of five was carried out and docking studies were performed between ligands and enzyme using 'Autodock4.2'.

RESULTS: Two phytochemical compounds SN00288228 and SN00226692 were predicted for the inhibition of AChE and BuChE, respectively. The docking results revealed Ajmalicine, a prominent natural alkaloid, showing promising inhibitory potential against AChE and BuChE with the binding energy of -9.02 and -8.89 kcal/mole, respectively. However, SN00288228- AChE, and SN00226692-BuChE were found to have binding energy -9.88 and -9.54 kcal/mole, respectively. These selected phytochemical compounds showed better interactions in comparison to Ajmalicine with the target molecule.

CONCLUSION: The current study verifies that SN00288228 and SN00226692 are more capable inhibitors of human AChE and BuChE as compared to Ajmalicine with reference to ΔG values.

Matched MeSH terms: Ligands

Fulltext Chirogenesis and Pfeiffer Effect in Optically Inactive EuIII and TbIII Tris(β-diketonate) Upon Intermolecular Chirality Transfer From Poly- and Monosaccharide Alkyl Esters and α-Pinene: Emerging Circularly Polarized Luminescence (CPL) and Circular Dichroism (CD)

Fujiki M, Wang L, Ogata N, Asanoma F, Okubo A, Okazaki S, et al.

Front Chem, 2020;8:685.

PMID: 32903703 DOI: 10.3389/fchem.2020.00685

We report emerging circularly polarized luminescence (CPL) at 4f-4f transitions when lanthanide (EuIII and TbIII) tris(β-diketonate) embedded to cellulose triacetate (CTA), cellulose acetate butyrate (CABu), D-/L-glucose pentamethyl esters ( D-/ L-Glu), and D-/L-arabinose tetramethyl esters ( D-/ L-Ara) are in film states. Herein, 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate (fod) and 2,2,6,6-tetramethyl-3,5-heptanedione (dpm) were chosen as the β-diketonates. The glum value of Eu(fod)3 in CABu are +0.0671 at 593 nm (5

D

0

→

7

F1) and -0.0059 at 613 nm (5

D

0

→

7

F2), respectively, while those in CTA are +0.0463 and -0.0040 at these transitions, respectively. The glum value of Tb(fod)3 in CABu are -0.0029 at 490 nm (5

D

4

→

7

F6), +0.0078 at 540 nm (5

D

4

→

7

F5), and -0.0018 at 552 nm (5

D

4

→

7

F5), respectively, while those in CTA are -0.0053, +0.0037, and -0.0059 at these transitions, respectively. D-/ L-Glu and D-/ L-Ara induced weaker glum values at 4f-4f transitions of Eu(fod)3, Tb(fod)3, and Tb(dpm)3. For comparison, Tb(dpm)3 in α-pinene showed clear CPL characteristics, though Eu(dpm)3 did not. A surplus charge neutralization hypothesis was applied to the origin of attractive intermolecular interactions between the ligands and saccharides. This idea was supported from the concomitant opposite tendency in upfield 19F-NMR and downfield 1H-NMR chemical shifts of Eu(fod)3 and the opposite Mulliken charges between F-C bonds (fod) and H-C bonds (CTA and D-/ L-Glu). An analysis of CPL excitation (CPLE) and CPL spectra suggests that (+)- and (-)-sign CPL signals of EuIII and TbIII at different 4f-4f transitions in the visible region are the same with the (+)-and (-)-sign exhibited by CPLE bands at high energy levels of EuIII and TbIII in the near-UV region.

Matched MeSH terms: Ligands

G protein-coupled estrogen receptor-1: homology modeling approaches and application in screening new GPER-1 modulators

Khan SU, Ahemad N, Chuah LH, Naidu R, Htar TT

J Biomol Struct Dyn, 2020 Nov 08.

PMID: 33164654 DOI: 10.1080/07391102.2020.1844059

G protein-coupled receptors (GPCRs) belong to the largest family of protein targets comprising over 800 members in which at least 500 members are the therapeutic targets. Among the GPCRs, G protein-coupled estrogen receptor-1 (GPER-1) has shown to have the ability in estrogen signaling. As GPER-1 plays a critical role in several physiological responses, GPER-1 has been considered as a potential therapeutic target to treat estrogen-based cancers and other non-communicable diseases. However, the progress in the understanding of GPER-1 structure and function is relatively slow due to the availability of a only a few selective GPER-1 modulators. As with many GPCRs, the X-ray crystal structure of GPER-1 is yet to be resolved and thus has led the researchers to search for new GPER-1 modulators using homology models of GPER-1. In this review, we aim to summarize various approaches used in the generation of GPER-1 homology model and their applications that have resulted in new GPER-1 ligands.

Matched MeSH terms: Ligands

Fulltext Synthesis, characterizations and anti-corrosion screening of Sadimine and Brosadamine

Siti Noriah Mohd Shotor, Nur Anis Atirah Zulkiflee

Journal of Academia Universiti Teknologi MARA Negeri Sembilan, 2020;8(2):1-8.

MyJurnal

This paper deals with a review of the inhibition activity of a Schiff bases on the deterioration of mild steel in hydrochloric acid media. Two Schiff base ligands namely N,N’- Bis(salicylidene) ethylenediamine (Sadimine) and N,N’-Bis(bromosalicylidene)- ethylenediamine (Brosadimine) were synthesized from the condensation reactions of salicylaldehyde or 5-bromosalicylaldehyde with ethylenediamine respectively and evaluated as corrosion inhibitor for mild steel in 1 M HCl solution using weight loss method. The use of inhibitors is one of the most practical methods for protection of mild steel against corrosion in acidic media. Schiff bases are widely being employed in such applications. This paper highlights the influence of structure–inhibition activity relationship of Schiff base compounds
on their performance as corrosion inhibitors of mild steel in acid media. Sadimine and
Brosadimine show appreciable corrosion inhibition efficiency against the corrosion of mild
steel in 1 M HCl solution at room temperature. It has been found that Brosadimine shows
greater corrosion inhibition efficiency than Sadimine due to extra halogen group presence in
the structure. As the concentration of studied inhibitors increases, the corrosion inhibition
efficiency of the prepared compounds also increases. This study demonstrated that corrosion
inhibitors for metals and alloys can preserve the quality and life of metals from corrosion.

Matched MeSH terms: Ligands

In silico approach for Post-SELEX DNA aptamers: A mini-review

Ahmad NA, Mohamed Zulkifli R, Hussin H, Nadri MH

J Mol Graph Model, 2021 06;105:107872.

PMID: 33765525 DOI: 10.1016/j.jmgm.2021.107872

Aptamers are short oligonucleotides that possess high specificity and affinity against their target. Generated via Systematic Evolution of Ligands by Exponential Enrichment, (SELEX) in vitro, they were screened and enriched. This review covering the study utilizing bioinformatics tools to analyze primary sequence, secondary and tertiary structure prediction, as well as docking simulation for various aptamers and their ligand interaction. Literature was pooled from Web of Science (WoS) and Scopus databases until December 18, 2020 using specific search string related to DNA aptamers, in silico, structure prediction, and docking simulation. Out of 330 published articles, 38 articles were assessed in the analysis based on the predefined inclusion and exclusion criteria. It was found that Mfold and RNA Composer web server is the most popular tool in secondary and tertiary structure prediction of DNA aptamers, respectively. Meanwhile, in docking simulation, ZDOCK and AutoDock are preferred to analyze binding interaction in the aptamer-ligand complex. This review reports a brief framework of recent developments of in silico approaches that provide predictive structural information of ssDNA aptamer.

Matched MeSH terms: Ligands

Discovery of new targeting agents against GAPDH receptor for antituberculosis drug delivery

Noh MAA, Fazalul Rahiman SS, A Wahab H, Mohd Gazzali A

J Basic Clin Physiol Pharmacol, 2021 Jun 25;32(4):715-722.

PMID: 34214294 DOI: 10.1515/jbcpp-2020-0435

OBJECTIVES: Tuberculosis (TB) remains a public health concern due to the emergence and evolution of multidrug-resistant strains. To overcome this issue, reinforcing the effectiveness of first line antituberculosis agents using targeted drug delivery approach is an option. Glyceraldehyde-3-Phosphate Dehydrogenase (GADPH), a common virulence factor found in the pathogenic microorganisms has recently been discovered on the cell-surface of Mycobacterium tuberculosis, allowing it to be used as a drug target for TB. This study aims to discover active small molecule(s) that target GAPDH and eventually enhance the delivery of antituberculosis drugs.

METHODS: Ten ligands with reported in vitro and/or in vivo activities against GAPDH were evaluated for their binding interactions through molecular docking studies using AutoDock 4.2 program. The ligand with the best binding energy was then modified to produce 10 derivatives, which were redocked against GAPDH using previous protocols. BIOVIA Discovery Studio Visualizer 2019 was used to explore the ligand-receptor interactions between the derivatives and GAPDH.

RESULTS: Among the 10 ligands, curcumin, koningic acid and folic acid showed the best binding energies. Further analysis on the docking of two folic acid derivatives, F7 (γ-{[tert-butyl-N-(6-aminohexyl)]carbamate}folic acid) and F8 (folic acid N-hydroxysuccinimide ester) showed that the addition of a bulky substituent at the carboxyl group of the glutamic acid subcomponent resulted in improved binding energy.

CONCLUSIONS: Folic acid and the two derivatives F7 and F8 have huge potentials to be developed as targeting agents against the GAPDH receptor. Further study is currently on-going to evaluate the effectiveness of these molecules in vitro.

Matched MeSH terms: Ligands

New fragment weighting scheme for the Bayesian inference network in ligand-based virtual screening

Abdo A, Salim N

J Chem Inf Model, 2011 Jan 24;51(1):25-32.

PMID: 21155550 DOI: 10.1021/ci100232h

Many of the conventional similarity methods assume that molecular fragments that do not relate to biological activity carry the same weight as the important ones. One possible approach to this problem is to use the Bayesian inference network (BIN), which models molecules and reference structures as probabilistic inference networks. The relationships between molecules and reference structures in the Bayesian network are encoded using a set of conditional probability distributions, which can be estimated by the fragment weighting function, a function of the frequencies of the fragments in the molecule or the reference structure as well as throughout the collection. The weighting function combines one or more fragment weighting schemes. In this paper, we have investigated five different weighting functions and present a new fragment weighting scheme. Later on, these functions were modified to combine the new weighting scheme. Simulated virtual screening experiments with the MDL Drug Data Report (23) and maximum unbiased validation data sets show that the use of new weighting scheme can provide significantly more effective screening when compared with the use of current weighting schemes.

Matched MeSH terms: Ligands

Fulltext Ligand-based virtual screening using Bayesian networks

Abdo A, Chen B, Mueller C, Salim N, Willett P

J Chem Inf Model, 2010 Jun 28;50(6):1012-20.

PMID: 20504032 DOI: 10.1021/ci100090p

A Bayesian inference network (BIN) provides an interesting alternative to existing tools for similarity-based virtual screening. The BIN is particularly effective when the active molecules being sought have a high degree of structural homogeneity but has been found to perform less well with structurally heterogeneous sets of actives. In this paper, we introduce an alternative network model, called a Bayesian belief network (BBN), that seeks to overcome this limitation of the BIN approach. Simulated virtual screening experiments with the MDDR, WOMBAT and MUV data sets show that the BIN and BBN methods allow effective screening searches to be carried out. However, the results obtained are not obviously superior to those obtained using a much simpler approach that is based on the use of the Tanimoto coefficient and of the square roots of fragment occurrence frequencies.

Matched MeSH terms: Ligands

Fulltext In Silico Drug Design of Anti-Breast Cancer Agents

Rajagopal K, Kalusalingam A, Bharathidasan AR, Sivaprakash A, Shanmugam K, Sundaramoorthy M, et al.

Molecules, 2023 May 18;28(10).

PMID: 37241915 DOI: 10.3390/molecules28104175

Cancer is a condition marked by abnormal cell proliferation that has the potential to invade or indicate other health issues. Human beings are affected by more than 100 different types of cancer. Some cancer promotes rapid cell proliferation, whereas others cause cells to divide and develop more slowly. Some cancers, such as leukemia, produce visible tumors, while others, such as breast cancer, do not. In this work, in silico investigations were carried out to investigate the binding mechanisms of four major analogs, which are marine sesquiterpene, sesquiterpene lactone, heteroaromatic chalcones, and benzothiophene against the target estrogen receptor-α for targeting breast cancer using Schrödinger suite 2021-4. The Glide module handled the molecular docking experiments, the QikProp module handled the ADMET screening, and the Prime MM-GB/SA module determined the binding energy of the ligands. The benzothiophene analog BT_ER_15f (G-score -15.922 Kcal/mol) showed the best binding activity against the target protein estrogen receptor-α when compared with the standard drug tamoxifen which has a docking score of -13.560 Kcal/mol. TRP383 (tryptophan) has the highest interaction time with the ligand, and hence it could act for a long time. Based on in silico investigations, the benzothiophene analog BT_ER_15f significantly binds with the active site of the target protein estrogen receptor-α. Similar to the outcomes of molecular docking, the target and ligand complex interaction motif established a high affinity of lead candidates in a dynamic system. This study shows that estrogen receptor-α targets inhibitors with better potential and low toxicity when compared to the existing market drugs, which can be made from a benzothiophene derivative. It may result in considerable activity and be applied to more research on breast cancer.

Matched MeSH terms: Ligands

A new sensitive electrochemical method for the determination of vanadium(IV) and vanadium(V) in Benfield sample

Qureshi MS, Mohd Yusoff AR, Shah A, Nafady A, Sirajuddin

Talanta, 2015 Jan;132:541-7.

PMID: 25476342 DOI: 10.1016/j.talanta.2014.10.005

Vanadium(IV) and vanadium(V) can be determined by using differential pulse cathodic stripping voltammetry technique (DPCSV). Cupferron (ammonium N-nitrosophenylhydroxylamine) was used as ligand to form complex compounds with vanadium ions in Britton-Robinson buffer (BRB) solution. At concentration lower than 1.0×10(-6) M, both V(IV) and V(V) cupferron complexes showed a single cathodic peak at -0.576 V in BRB of pH 4; thus V(IV) and V(V) ions cannot be differentiated at low concentration. However, the ionic species of vanadium can be differentiated at high concentration in the presence of cupferron. Parameters including pH of BRB solution, initial potential and accumulation potential were optimized. Under the optimized parameters, the limit of detection (LOD) was 0.09 nM, and the peak current was linear in the concentration range 0.01-0.9 µM total vanadium ions. The determination of V(IV) and V(V) ions was carried out at higher concentration in the sample using calibration plot method. At higher concentration range of 10-60 µM V(IV) and V(V) ions were determined with LOD of 1.2 and 1.1 µM, respectively. The developed method was successfully applied to 10,00,000 fold diluted Benfield sample and 0.6227 M total vanadium ions were determined. The determination of V(IV) and V(V) ions were also successfully carried out in artificial sample as well as Benfield sample (dilution factor, 10,000). The concentration of V(IV) and V(V) ions was 22.52 µM and 38.91 µM, respectively, giving total vanadium concentration of 0.6143 M in Benfield sample.

Matched MeSH terms: Ligands

Fulltext Diorganotin(IV) derivatives of N-methyl p-fluorobenzo-hydroxamic acid: preparation, spectral characterization, X-ray diffraction studies and antitumor activity

Naqeebullah, Farina Y, Chan KM, Mun LK, Rajab NF, Ooi TC

Molecules, 2013 Jul 22;18(7):8696-711.

PMID: 23881054 DOI: 10.3390/molecules18078696

Three diorganotin(IV) complexes of the general formula R2Sn[RcC(O)N(RN)O] (Rc = aryl, RN = Alkyl) have been synthesized by refluxing in toluene the corresponding diorganotin(IV) oxides with the free ligand N-methyl p-fluorobenzohydroxamic acid, using a Dean and Stark water separator. The ligand was derived from the reaction of the corresponding p-fluorobenzoyl chloride and N-methylhydroxylamine hydrochloride in the presence of sodium hydrogen carbonate. The isolated free ligand and its respective diorganotin compounds have been characterized by elemental analysis, IR and 1H-, 13C-, 119Sn-NMR spectroscopies. The crystal structures of the diorganotin complexes have been confirmed by single crystal X-ray diffraction methods. The investigations carried out on the diorganotin(IV) complexes of N-methyl p-fluorobenzohydroxamic acid confirmed a 1:2 stoichiometry. The complex formation took place through the O,O-coordination via the carbonyl oxygen and subsequent deprotonated hydroxyl group to the tin atom. The crystal structures of three diorganotin complexes were determined and were found to adopt six coordination geometries at the tin centre with coordination to two ligand moieties.

Matched MeSH terms: Ligands

Fulltext Adapting Document Similarity Measures for Ligand-Based Virtual Screening

Himmat M, Salim N, Al-Dabbagh MM, Saeed F, Ahmed A

Molecules, 2016 Apr 13;21(4):476.

PMID: 27089312 DOI: 10.3390/molecules21040476

Quantifying the similarity of molecules is considered one of the major tasks in virtual screening. There are many similarity measures that have been proposed for this purpose, some of which have been derived from document and text retrieving areas as most often these similarity methods give good results in document retrieval and can achieve good results in virtual screening. In this work, we propose a similarity measure for ligand-based virtual screening, which has been derived from a text processing similarity measure. It has been adopted to be suitable for virtual screening; we called this proposed measure the Adapted Similarity Measure of Text Processing (ASMTP). For evaluating and testing the proposed ASMTP we conducted several experiments on two different benchmark datasets: the Maximum Unbiased Validation (MUV) and the MDL Drug Data Report (MDDR). The experiments have been conducted by choosing 10 reference structures from each class randomly as queries and evaluate them in the recall of cut-offs at 1% and 5%. The overall obtained results are compared with some similarity methods including the Tanimoto coefficient, which are considered to be the conventional and standard similarity coefficients for fingerprint-based similarity calculations. The achieved results show that the performance of ligand-based virtual screening is better and outperforms the Tanimoto coefficients and other methods.

Matched MeSH terms: Ligands

SELEX Modifications and Bioanalytical Techniques for Aptamer-Target Binding Characterization

Tan SY, Acquah C, Sidhu A, Ongkudon CM, Yon LS, Danquah MK

Crit Rev Anal Chem, 2016 Nov;46(6):521-37.

PMID: 26980177 DOI: 10.1080/10408347.2016.1157014

The quest to improve the detection of biomolecules and cells in health and life sciences has led to the discovery and characterization of various affinity bioprobes. Libraries of synthetic oligonucleotides (ssDNA/ssRNA) with randomized sequences are employed during Systematic Evolution of Ligands by Exponential Enrichment (SELEX) to select highly specific affinity probes called aptamers. With much focus on the generation of aptamers for a variety of target molecules, conventional SELEX protocols have been modified to develop new and improved SELEX protocols yielding highly specific and stable aptamers. Various techniques have been used to analyze the binding interactions between aptamers and their cognate molecules with associated merits and limitations. This article comprehensively reviews research advancements in the generation of aptamers, analyses physicochemical conditions affecting their binding characteristics to cellular and biomolecular targets, and discusses various field applications of aptameric binding. Biophysical techniques employed in the characterization of the molecular and binding features of aptamers to their cognate targets are also discussed.

Matched MeSH terms: Ligands

Fulltext Crystal structures of (2,2'-bipyridyl-κ(2) N,N')bis-[N,N-bis-(2-hydroxy-eth-yl)di-thio-carbamato-κ(2) S,S']zinc dihydrate and (2,2'-bipyridyl-κ(2) N,N')bis-[N-(2-hydroxy-eth-yl)-N-iso-propyl-dithio-carbamato-κ(2) S,S']zinc

Safbri SA, Halim SN, Tiekink ER

Acta Crystallogr E Crystallogr Commun, 2016 Feb 1;72(Pt 2):203-8.

PMID: 26958388 DOI: 10.1107/S2056989016000700

The common feature of the title compounds, [Zn(C5H10NO2S2)2(C10H8N2)]·2H2O, (I), and [Zn(C6H12NOS2)2(C10H8N2)], (II), is the location of the Zn(II) atoms on a twofold rotation axis. Further, each Zn(II) atom is chelated by two symmetry-equivalent and symmetrically coordinating di-thio-carbamate ligands and a 2,2'-bi-pyridine ligand. The resulting N2S4 coordination geometry is based on a highly distorted octa-hedron in each case. In the mol-ecular packing of (I), supra-molecular ladders mediated by O-H⋯O hydrogen bonding are found whereby the uprights are defined by {⋯HO(water)⋯HO(hy-droxy)⋯} n chains parallel to the a axis and with the rungs defined by 'Zn[S2CN(CH2CH2)2]2'. The water mol-ecules connect the ladders into a supra-molecular layer parallel to the ab plane via water-O-H⋯S and pyridyl-C-H⋯O(water) inter-actions, with the connections between layers being of the type pyridyl-C-H⋯S. In (II), supra-molecular layers parallel to the ab plane are sustained by hy-droxy-O-H⋯S hydrogen bonds with connections between layers being of the type pyridyl-C-H⋯S.

Matched MeSH terms: Ligands

Fulltext Bis[N-(2-hy-droxy-eth-yl)-N-iso-propyl-dithio-carbamato-κ(2) S,S'](piperazine-κN)cadmium: crystal structure and Hirshfeld surface analysis

Safbri SA, Halim SN, Jotani MM, Tiekink ER

Acta Crystallogr E Crystallogr Commun, 2016 Feb 1;72(Pt 2):158-63.

PMID: 26958378 DOI: 10.1107/S2056989016000165

The title compound, [Cd(C6H12NOS2)2(C4H10N2)], features a distorted square-pyramidal coordination geometry about the central Cd(II) atom. The di-thio-carbamate ligands are chelating, forming similar Cd-S bond lengths and define the approximate basal plane. One of the N atoms of the piperazine mol-ecule, which adopts a chair conformation, occupies the apical site. In the crystal, supra-molecular layers propagating in the ac plane are formed via hy-droxy-O-H⋯O(hy-droxy), hy-droxy-O-H⋯N(terminal-piperazine) and coordinated-piperazine-N-H⋯O(hy-droxy) hydrogen bonds; the layers also feature methine-C-H⋯S inter-actions and S⋯S [3.3714 (10) Å] short contacts. The layers stack along the b-axis direction with very weak terminal-piperazine-N-H⋯O(hy-droxy) inter-actions between them. An evaluation of the Hirshfeld surfaces confirms the importance of inter-molecular inter-actions involving oxygen and sulfur atoms.

Matched MeSH terms: Ligands

Aptamer-based 'point-of-care testing'

Gopinath SC, Lakshmipriya T, Chen Y, Phang WM, Hashim U

Biotechnol Adv, 2016 May-Jun;34(3):198-208.

PMID: 26876017 DOI: 10.1016/j.biotechadv.2016.02.003

Aptamers are single-stranded oligonucleotides that can be artificially generated by a method called Systematic evolution of ligands by exponential enrichment (SELEX). The generated aptamers have been assessed for high-performance sensing applications due to their appealing characteristics. With either aptamers alone or complementing with antibodies, several high sensitive and portable sensors have been demonstrated for use in 'point-of-care testing'. Due to their high suitability and flexibility, aptamers are conjugated with nanostructures and utilized in field applications. Moreover, aptamers are more amenable to chemical modifications, making them capable of utilization with most developed sensors. In this overview, we discuss novel, portable, and aptamer-based sensing strategies that are suitable for 'point-of-care testing'.

Matched MeSH terms: Ligands

Fulltext Protease-targeting peptide-functionalized porous silicon nanoparticles for cancer fluorescence imaging

Kanathasan JS, Palanisamy UD, Radhakrishnan AK, Chakravarthi S, Thong TB, Swamy V

Nanomedicine (Lond), 2022 Sep;17(21):1511-1528.

PMID: 36382634 DOI: 10.2217/nnm-2022-0017

Background: Porous silicon (pSi) nanoparticles (NPs) functionalized with suitable targeting ligands are now established cancer bioimaging agents and drug-delivery platforms. With growing interest in peptides as tumor-targeting ligands, much work has focused on the use of various peptides in combination with pSi NPs for cancer theranostics. Here, the authors investigated the targeting potential of pSi NPs functionalized with two types of peptide, a linear 10-mer peptide and its branched (Y-shaped) equivalent, that respond to legumain activity in tumor cells. Results: In vitro experiments established that the linear peptide-pSi NP conjugate had better aqueous stability under tumor conditions and higher binding efficiency (p 0.05) of linear peptide-conjugated pSi NPs in the tumor site within 4 h compared with nonconjugated pSi NPs. These results suggest that the linear peptide-pSi NP formulation is a nontoxic, stable and efficient fluorescence bioimaging agent and potential drug-delivery platform.

Matched MeSH terms: Ligands

Fulltext Pea eggplant (Solanum torvum Swartz) is a source of plant food polyphenols with SARS-CoV inhibiting potential

Govender N, Zulkifli NS, Badrul Hisham NF, Ab Ghani NS, Mohamed-Hussein ZA

PeerJ, 2022;10:e14168.

PMID: 36518265 DOI: 10.7717/peerj.14168

BACKGROUND: Pea eggplant (Solanum torvum Swartz) commonly known as turkey berry or 'terung pipit' in Malay is a vegetable plant widely consumed by the local community in Malaysia. The shrub bears pea-like turkey berry fruits (TBFs), rich in phytochemicals of medicinal interest. The TBF phytochemicals hold a wide spectrum of pharmacological properties. In this study, the TBF phytochemicals' potential inhibitory properties were evaluated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of the Coronavirus disease 2019 (COVID-19). The TBF polyphenols were screened against SARS-CoV receptors via molecular docking and the best receptor-ligand complex was validated further by molecular dynamics (MD) simulation.

METHOD: The SARS-CoV receptor structure files (viral structural components) were retrieved from the Protein Data Bank (PDB) database: membrane protein (PDB ID: 3I6G), main protease (PDB ID: 5RE4), and spike glycoproteins (PDB ID: 6VXX and 6VYB). The receptor binding pocket regions were identified by Discovery Studio (BIOVIA) for targeted docking with TBF polyphenols (genistin, kaempferol, mellein, rhoifolin and scutellarein). The ligand and SARS-CoV family receptor structure files were pre-processed using the AutoDock tools. Molecular docking was performed with the Lamarckian genetic algorithm using AutoDock Vina 4.2 software. The best pose (ligand-receptor complex) from the molecular docking analysis was selected based on the minimum binding energy (MBE) and extent of structural interactions, as indicated by BIOVIA visualization tool. The selected complex was validated by a 100 ns MD simulation run using the GROMACS software. The dynamic behaviour and stability of the receptor-ligand complex were evaluated by the root mean square displacement (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), solvent accessible surface volume (SASV) and number of hydrogen bonds.

RESULTS: At RMSD = 0, the TBF polyphenols showed fairly strong physical interactions with SARS-CoV receptors under all possible combinations. The MBE of TBF polyphenol-bound SARS CoV complexes ranged from -4.6 to -8.3 kcal/mol. Analysis of the structural interactions showed the presence of hydrogen bonds, electrostatic and hydrophobic interactions between the receptor residues (RR) and ligands atoms. Based on the MBE values, the 3I6G-rhoifolin (MBE = -8.3 kcal/mol) and 5RE4-genistin (MBE = -7.6 kcal/mol) complexes were ranked with the least value. However, the latter showed a greater extent of interactions between the RRs and the ligand atoms and thus was further validated by MD simulation. The MD simulation parameters of the 5RE4-genistin complex over a 100 ns run indicated good structural stability with minimal flexibility within genistin binding pocket region. The findings suggest that S. torvum polyphenols hold good therapeutics potential in COVID-19 management.

Matched MeSH terms: Ligands

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