Synthesis,computational quantum chemical study,in silico ADMET and molecular docking analysis,in vitro biological evaluation of a novel sulfur heterocyclic thiophene derivative containing 1,2,3-triazole and pyridine moieties as a potential human topoisomerase IIα inhibiting anticancer agent

Computational quantum chemical study and biological evaluation of a synthesized novel sulfur heterocyclic thiophene derivative containing 1,2,3-triazole and pyridine moieties namely BTPT [2-(1-benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-6-methoxy-4-(thiophen-2-yl) pyridine] was presented in this study. The crystal structure was determined by SCXRD method. For the title compound BTPT, spectroscopic characterization like ¹H NMR, ¹³C NMR, FTIR, UV–vis were carried out theoretically by computational DFT method and compared with experimental data. Druglikeness parameters of BTPT were found through in silico pharmacological ADMET properties estimation. The molecular docking investigation was performed with human topoisomerase IIα (PDB ID:1ZXM) targeting ATP binding site. In vitro cytotoxicity activity of BTPT/doxorubicin were examined by MTT assay procedure against three human cancer cell lines A549, PC-3, MDAMB-231 with IC50 values of 0.68/0.70, 1.03/0.77 and 0.88/0.98 μM, respectively. Our title compound BTPT reveals notable cytotoxicity against breast cancer cell (MDAMB-231), moderate activity with human lung cancer cell (A-549) and less inhibition with human prostate cancer cell (PC-3) compared to familiar cancer medicine doxorubicin. From the results, BTPT could be observed as a potential candidate for novel anticancer drug development process.     

Synthesis,characterization, DNA binding,cytotoxicity and molecular docking properties of three novel butterfly-like complexes with nitrogen-containing heterocyclic ligands

Three novel complexes, namely [Nd·L₁·HCOO·(H₂O)₄] ( 1 ), [Pr·L₁·HCOO·(H₂O)₄] ( 2 ) and [In·L₂·Cl·(H₂O)₂] ( 3 ) (L₁ = 1,1-bis(5-(pyrazin-2-yl)-1,2,4-triazol-3-yl)methane, L₂ = 1,1-bis(5-(pyrazin-2-yl)-1,2,4-triazol-3-yl)ketone), were synthesized and characterized. The molecular structures of 1 – 3 were confirmed using single-crystal X-ray diffraction. All three obtained complexes are zero-dimensional and connected to each other by hydrogen bonds. In 1 and 2 the metal is surrounded by nine donors and 3 has seven coordination sites. The interaction of 1 – 3 with calf thymus DNA (CT-DNA) was explored using UV absorption spectra and fluorescence spectra. The intrinsic binding constants of 1 – 3 with CT-DNA are about 1.9 × 10⁴, 1.4 × 10⁴ and 1.1 × 10⁴, respectively. Stern–Volmer quenching plots of 1 – 3 have slopes of 0.1508, 0.134 and 0.1205, respectively. The ability of these complexes to cleave pBR322 plasmid DNA was demonstrated using gel electrophoresis assay. Apoptosis studies of the three novel complexes showed a significant inhibitory effect on HeLa cells. Furthermore, MTT assays were used to evaluate the anticancer activity of the three complexes. The cytotoxicity study indicated that complex 1 possesses a higher inhibitory rate of HeLa cells than the other complexes. Especially, the efficacy of 1 was shown to be the highest for cisplatin at 24 h. A further molecular docking technique was introduced to understand the binding of the complexes toward the target DNA.     

Brugnanin,a new syn-2,3-dihydrobenzofuran neolignan dioate from the mangrove <Emphasis Type="Italic">Bruguiera gymnorrhiza</Emphasis>

Brugnanin (1), a neolignan dioate, was isolated from a mangrove plant Bruguiera gymnorrhiza. Based on spectroscopic interpretation of MS, IR, and NMR data, 1 was elucidated as (7R*,8S*,E)-3-hydroxy-5,5′-dimethoxy-7-O-4′,8-3′-neolignan-7′-ene-9,9′-dioic acid dioctadecyl ester. MTT assay showed that 1 had weak inhibitory activity against growth of CNE-1 nasopharyngeal carcinoma cell line. Published in Khimiya Prirodnykh Soedinenii, No. 2, pp. 147–149, March–April, 2008.     

稀土元素对人肝癌细胞SMMC-7721增殖的影响

用MTT法研究了14种稀土元素(La，Ce，Pr，Nd，Sm，Eu，Gd，Tb，Dy，Ho，Er，Tm，Yb和Lu)对人肝癌细胞SMMC-7721增殖的影响。他们对肝癌细胞的生长作用可分为3类。其中La^3 、Ce^3 和Eu^3 对肝癌细胞的增殖有剂量依赖性正效应，能够在一定浓度范围内刺激细胞生长；Sm^3 ，Gd^3 ，Ho^3 ，Er^3 ，Yb^3 对肝癌细胞生长的刺激作用没有剂量依赖性特征；而Pr^3 ，Nd^3 ，Tb^3 ，Dy^3 ，Tm^3 和Lu^3 则表现出对肝癌细胞的增殖具有不用程度的抑制。推测14种稀土元素作用方式的不同与他们的原子结构有一定的关系，它们对肝癌细胞的相对增殖率随着原子序数的增加呈现出一定的规律性。     

N-取代苄基-4-羟基-4-取代哌啶衍生物的合成及初步抗白血病活性

为了寻找对白血病细胞系增殖有较高抑制活性的先导化合物,本文以取代苄胺为原料,经Michael加成,Dieckmann缩合,水解脱羧和与Grignard试剂反应合成了12个均未见文献报道的目标化合物6a─6l,结构均经过1H NMR、IR、MS及元素分析确证。并采用MTT法对目标化合物进行了对白血病K562细胞系增殖影响的初步测试,结果表明大部分具有较好的抑制细胞系增殖的活性,有潜在的抗白血病活性。     

Ratiometric fluorescence transduction by hybridization after isothermal amplification for determination of zeptomole quantities of oligonucleotide biomarkers with a paper-based platform and camera-based detection

Paper is a promising platform for the development of decentralized diagnostic assays owing to the low cost and ease of use of paper-based analytical devices (PADs). It can be challenging to detect on PADs very low concentrations of nucleic acid biomarkers of lengths as used in clinical assays. Herein we report the use of thermophilic helicase-dependent amplification (tHDA) in combination with a paper-based platform for fluorescence detection of probe-target hybridization. Paper substrates were patterned using wax printing. The cellulosic fibers were chemically derivatized with imidazole groups for the assembly of the transduction interface that consisted of immobilized quantum dot (QD)–probe oligonucleotide conjugates. Green-emitting QDs (gQDs) served as donors with Cy3 as the acceptor dye in a fluorescence resonance energy transfer (FRET)-based transduction method. After probe-target hybridization, a further hybridization event with a reporter sequence brought the Cy3 acceptor dye in close proximity to the surface of immobilized gQDs, triggering a FRET sensitized emission that served as an analytical signal. Ratiometric detection was evaluated using both an epifluorescence microscope and a low-cost iPad camera as detectors. Addition of the tHDA method for target amplification to produce sequences of ∼100 base length allowed for the detection of zmol quantities of nucleic acid targets using the two detection platforms. The ratiometric QD-FRET transduction method not only offered improved assay precision, but also lowered the limit of detection of the assay when compared with the non-ratiometric QD-FRET transduction method. The selectivity of the hybridization assays was demonstrated by the detection of single nucleotide polymorphism.     

A capacitive immunosensor for detection of cholera toxin

Contamination of food with biological toxins as well as their potential use as weapons of mass destruction has created an urge for rapid and cost effective analytical techniques capable of detecting trace amounts of these toxins. This paper describes the development of a sensitive method for detection of cholera toxin (CT) using a flow-injection capacitive immunosensor based on self-assembled monolayers. The sensing surface consists of monoclonal antibodies against the B subunit of CT (anti-CT), immobilized on a gold transducer. Experimental results show that the immunosensor responded linearly to CT concentrations in the range from 1.0 × 10⁻¹³ to 1.0 × 10⁻¹⁰ M under optimized conditions. The limit of detection (LOD) was 1.0 × 10⁻¹⁴ M. Two more analytical methods were employed for detection of CT using the same antibody namely, sandwich ELISA and surface plasmon resonance (SPR)-based immunosensor. The former had an LOD of 1.2 × 10⁻¹² M and a working range from 3.7 × 10⁻¹¹ to 2.9 × 10⁻¹⁰ M whereas, the later had an LOD of 1.0 × 10⁻¹¹ M and a linearity ranging from 1.0 × 10⁻⁹ to 1.0 × 10⁻⁶ M. These results demonstrate that the developed capacitive immunosensor system has a higher sensitivity than the other two techniques. The binding affinity of CT to the immobilized anti-CT was determined using the SPR-based immunosensor and an association constant (K_A) of 1.4 × 10⁹ M⁻¹ was estimated.     

In vitro and in silico study of Aloe vera leaf extract against human breast cancer

Abstract

Aloe vera leaf contains some bioactive compounds that have a strong binding affinity toward estrogen receptor as compared to standard drug tamoxifen. In this study, we have found that the IC₅₀ of Aloe vera leaf extract against breast cancer cell line (MCF-7) is 23?µg/mL which is much lower than the IC₅₀ (332?µg/mL) of Aloe vera leaf extract against non-cancerous cell line (NIH-3T3). We have also calculated the total concentration of phenolic acid (385.662?µg/mL), flavonoids (160.402?µg/mL) and alkaloids (276.754?µg/mL) in Aloe vera leaf extract. The free radical scavenging activity of Aloe vera leaf extract is 67% to 89% (at 50 to 300?µg/ml). Our virtual molecular docking study suggests that bioactive compounds like Aloe-emodin (?8.8?Kcal/mol), 7-hydroxy-2,5 dimethylchromone (?7.5?Kcal/mol), Beta-sitosterol (?7.3?Kcal/mol) etc. have a greater binding affinity toward estrogen alpha receptor as compared to standard drug Tamoxifen (?6.4?Kcal/mol).

     

High‐Throughput Mutational Analysis of a Twister Ribozyme

Recent discoveries of new classes of self‐cleaving ribozymes in diverse organisms have triggered renewed interest in the chemistry and biology of ribozymes. Functional analysis and engineering of ribozymes often involve performing biochemical assays on multiple ribozyme mutants. However, because each ribozyme mutant must be individually prepared and assayed, the number and variety of mutants that can be studied are severely limited. All of the single and double mutants of a twister ribozyme (a total of 10 296 mutants) were generated and assayed for their self‐cleaving activity by exploiting deep sequencing to count the numbers of cleaved and uncleaved sequences for every mutant. Interestingly, we found that the ribozyme is highly robust against mutations such that 71 % and 30 % of all single and double mutants, respectively, retain detectable activity under the assay conditions. It was also observed that the structural elements that comprise the ribozyme exhibit distinct sensitivity to mutations.