Solvent-Free Synthesis of Pyrimidine Nucleoside-Aminophosphonate Hybrids and Their Biological Activity Evaluation

A novel and highly efficient one-pot three-component synthesis of α-aminophosphonates under neat condition was developed. By employing this method, hybrid compounds of aminophosphonate with pyrimidine nucleosides were synthesized in good to excellent yields starting from 5-formyl-2′-deoxyuridine, aniline and dimethyl phosphite. The antiviral and antileishmanial activities of these novel hybrid compounds were also studied but none were found to be active.     

Synthesis and Biological Evaluation of Novel Carbazole Hybrids as Promising Antimicrobial Agents

Two series of carbazole analogs of 8‐methoxy‐N‐substituted‐9H‐carbazole‐3‐carboxamides (series 1) and carbazolyl substituted rhodanines (series 2) were synthesized through facile synthetic routes. All the final compounds from these two series were evaluated for their preliminary in vitro antifungal and antibacterial activity against four fungal (Candida albicans, Cryptococcus neoformans, Cryptococcus tropicalis and Aspergillus niger) and four bacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) strains, respectively. Among the tested compounds, three compounds of series 1 displayed promising antifungal and antibacterial activity, especially against C. neoformans and S. aureus. In addition, one compound of series 1 displayed notable antimicrobial activity (MIC: 6.25 μg/mL) against clinical isolates of C. albicans and C. neoformans (MIC: 12.5 μg/mL). From the second series, four compounds exhibited significant antifungal and antibacterial activity, especially against C. neoformans and S. aureus. The most active compound of series 2 displayed a prominent antimicrobial activity against C. neoformans (MIC: 3.125 μg/mL) and S. aureus (MIC: 1.56 μg/mL), respectively.     

Design,Synthesis, and Biological Evaluation of Novel Amyl Ester Tethered Dihydroartemisinin-Isatin Hybrids as Potent Anti-Breast Cancer Agents

A series of novel amyl ester tethered dihydroartemisinin-isatin hybrids 4a–d and 5a–h were designed, synthesized, and evaluated as anti-breast cancer agents. The synthesized hybrids were preliminarily screened against estrogen receptor-positive (MCF-7 and MCF-7/ADR) and triple-negative (MDA-MB-231 and) breast cancer cell lines. Three hybrids 4a , d and 5e not only were more potent than artemisinin and adriamycin against drug-resistant MCF-7/ADR and MDA-MB-231/ADR breast cancer cell lines, but also displayed non-cytotoxicity towards normal MCF-10 A breast cells, and the SI values were >4.15, indicating their excellent selectivity and safety profiles. Thus, hybrids 4a , d and 5e could act as potential anti-breast cancer candidates and were worthy of further preclinical evaluations. Moreover, the structure–activity relationships which may facilitate further rational design of more effective candidates were also enriched.     

Design,Synthesis, Antimicrobial Evaluation and in Silico Studies of Eugenol-Sulfonamide Hybrids

Using molecular hybridization, specific sulfonamide derivatives of eugenol were synthesized with subtle modifications in the allylic chain of the eugenol subunit (and also in the nature of the substituent group in the sulfonamide aromatic ring) which allowed us to study the influence of structural changes on the antimicrobial potential of the hybrids. Antimicrobial test results showed that most of the synthesized hybrid compounds showed good activity with better results than the parent compounds. Molecular docking studies of the hybrids with the essential bacterial enzyme DHPS showed complexes with low binding energies, suggesting that DHPS could be a possible target for the antibacterial sulfonamide-eugenol hybrids. Furthermore, most of the final compounds presented similar docking poses to that of the crystallographic ligand sulfamethoxazole. The results obtained allow us to conclude that these are promising compounds for use as new leads in the search for new antibacterial sulfonamides.     

Synthesis,Design, and Biological Evaluation of Novel Diethylphenylcarbamothioylphosphonate

Russian Journal of Bioorganic Chemistry - The aim of this work was to synthesize a diethyl phenylcarbamothioyl phosphonate (EThmP) and evaluate its biological activities. ThmP has been prepared...     

Design and Biological Evaluation of New Mechanismbased Inhibitors of S-Adenosyl-L-homocysteine Hydrolase

Abstract

Geminal dihalohomovinyl 2 and haloacetylenic 4 analogs derived from adenosine were prepared. These compounds exhibited type II (covalent) mechanism-based inactivation of S-adenosyl-L-homocysteine hydrolase.     

Hybrids of Human and Monkey Adenoviruses (Adeno-Adeno Hybrids) That Can Reproduce in Monkey Cells: Biological and Molecular Genetic Peculiarities

A highly oncogenic monkey adenovirus SA7(C8) facilitates the reproduction of human adenovirus type 2 (Ad2) in monkey cells. Upon mixed infection of monkey cells with both viruses, these viruses recombine producing defective adeno-adeno hybrids Ad2C8 serologically identical to Ad2 and capable of assisting Ad2 to reproduce in monkey cells. Ad2C8 and Ad2 form an intercomplementary pair inseparable in monkey cells. Unlike oncogenic SA7(C8), Ad2C8 is a nononcogenic virus for hamsters but is able to induce tumor antigens of this virus (T and TSTA). Molecular genetic analysis of 68 clones of adeno-adeno hybrids revealed that the left part of their genome consists of Ad2 DNA, and the right part contains no less than 40% of the viral SA7(C8) genome where E2A, E3, and E4 genes are located. Apparently, the products of these genes contribute to the composition of adenoviral tumor antigens, while the E4 gene is involved in complementation of monkey and human adenoviruses and makes a contribution to host range determination of these viruses.     

Synthesis and Biological Activities of Novel (Z)-/(E)-Anisaldehyde-Based Oxime Ester Compounds

In search of novel natural product-based bioactive molecules, twenty (ten pairs) novel (Z)-/(E)-anisaldehyde-based oxime ester compounds were designed and synthesized by using anisaldehyde as starting material. Structural characterization of the target compounds was carried out by NMR, FT-IR, ESI-MS, and elemental analysis. Their herbicidal and antifungal activities were preliminarily tested. As a result, at 50 μg/mL, compound (E)- 5b exhibited excellent to good inhibition rates of 92.3 %, 79.2 %, and 73.9 %, against Rhizoctonia solani, Fusarium oxysporum f. sp. cucumerinum, and Bipolaris maydis, respectively, better than or comparable to that of the positive control chlorothalonil. In addition, at 100 μg/mL, compounds (E)- 5b , (E)- 5f , (Z)- 5f and (E)- 5d exhibited excellent to good inhibition rates of 85.8 %, 82.9 %, 78.6 % and 64.2 %, respectively, against the root-growth of rape (B. campestris), much better than that of the positive control flumioxazin. The bioassay result also showed that the synthesized compounds had obvious differences in antifungal and herbicidal activities between (Z)- and (E)-isomers. Preliminary structure–activity relationship was also discussed by theoretical calculation.     

Biological Evaluation of Carpeting

Studies of microbial contamination were carried out on a carpet strip (acrilan) installed in a laboratory corridor and on two carpet strips (acrilan and wool) installed in two rooms in a pediatric hospital. A sampling procedure of randomly removing 8-mm plugs from the carpets was used for subsequent enumeration and identification of contaminating microorganisms. Microbial counts increased with time, reached a "plateau" at about 4 weeks, and appeared to be related to the amount of activity present in the carpeted area. Vacuuming of carpets showed only a slight reduction in the number of recoverable microorganisms. Qualitative studies on a strip of acrilan carpet installed in a hospital room indicated that Staphylococcus epidermidis and gram-positive nonsporeforming rods were the predominating microorganisms. Coagulase-positive S. aureus organisms were isolated during every sampling period, and gram-negative rods were also regularly isolated. Most nitrate-reducing gram-negative rods belonged to the Enterobacter and Escherichia groups. Survival studies conducted on carpet strips after hospital installation showed relatively constant levels of contamination for about 6 weeks, followed by a gradual reduction in numbers; coagulase-positive S. aureus were found for 35 days, whereas the proportions of most organisms remained relatively constant with time.     

Design,Synthesis, and Biological Evaluation of a Novel Series of Pirfenidone Derivatives

Russian Journal of Bioorganic Chemistry - In this study, a series of novel pirfenidone derivatives were designed and synthesized, and their activities against pulmonary fibrosis were evaluated. The...     

Design,Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists

By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relationships (SARs) of target compounds were concluded in this study, and five compounds were found to exhibited medium to potent CCR5 fusion activities with IC₅₀ values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC₅₀ value of 6.29 µM and an anti-HIV-1 inhibitor with an IC₅₀ value of 0.44 µM.     

葡萄种间杂交砧木育种F_1代植株耐盐性分析

以耐盐性较强的砧木1103P为对照品种,对左山一×SO4杂种砧木F1代的6个株系(A15、A17、A34、A35、A38和A48)及左山一×101-1杂种F1代2个株系(B24和B26)的一年生盆栽扦插苗进行100 mmol·L–1 NaCl胁迫处理,以各自无盐胁迫为对照处理。20天后,根据表型计算盐害指数,测定叶绿素含量、光合气体交换参数、叶绿素荧光参数以及生长量指标;以各项生长指标的耐盐系数为耐盐指标,通过主成分分析、相关性分析、隶属函数分析和聚类分析等方法对葡萄株系进行综合评价。结果表明,A34和A35植株无盐害症状,盐害级数为0;A15和A17植株有少部分叶片边缘焦枯,盐害级数为1。盐胁迫大幅度降低了1103P和B26等株系的叶绿素含量、光合速率、新梢生长量和生物量;而A15、A17、A34和A35植株的各项指标降低幅度较小。将生物量等12个单项指标转换成3个相互独立的综合指标,通过聚类分析,发现A34、A35、A15和A17植株的耐盐性较强,A38、A48和B24植株的耐盐性中等,1103P和B26植株的耐盐性较弱,与盐害分级结果一致。     

Design, Synthesis, and Biological Evaluation of Novel cRGD-Paclitaxel Conjugates for Integrin-Assisted Drug Delivery

The efficacy of taxane-based antitumor therapy is limited by several drawbacks which result in a poor therapeutic index. Thus, the development of approaches that favor selective delivery of taxane drugs (e.g., paclitaxel, PTX) to the disease area represents a truly challenging goal. On the basis of the strategic role of integrins in tumor cell survival and tumor progression, as well as on integrin expression in tumors, novel molecular conjugates were prepared where PTX is covalently attached to either cyclic AbaRGD (Azabicycloalkane-RGD) or AmproRGD (Aminoproline-RGD) integrin-recognizing matrices via structurally diverse connections. Receptor-binding assays indicated satisfactory-to-excellent α(V)β(3) binding capabilities for most conjugates, while in vitro growth inhibition assays on a panel of human tumor cell lines revealed outstanding cell sensitivity values. Among the nine conjugate ensemble, derivative 21, bearing a robust triazole ring connected to ethylene glycol units by an amide function and showing excellent cell sensitivity properties, was selected for in vivo studies in an ovarian carcinoma model xenografted in immunodeficient mice. Remarkable antitumor activity was attained, superior to that of PTX itself, which was associated with a marked induction of aberrant mitoses, consistent with the mechanism of action of spindle poisons. Overall, the novel cRGD-PTX conjugates disclosed here represent promising candidates for further advancement in the domain of targeted antitumor therapy.     

Design,Synthesis, Biological Activity Evaluation and Action Mechanism of Myricetin Derivatives Containing Thiazolebisamide

The plant diseases caused by a variety of pathogens such as viruses, bacteria and fungi pose a great threat to global food production and food safety. Therefore, the search for green, efficient and pollution-free pesticides has become an important task. In this article, 23 myricetin derivatives containing thiazolebisamides active groups have been designed and synthesized. Their activities were evaluated by performing in vitro antibacterial and in vivo antiviral assays, microscale thermophoresis (MST) and molecular docking assays. The results of in vivo antiviral assays showed that compounds A4 and A23 exhibited good antiviral activity with EC₅₀ values of 79.0 and 54.1 μg/mL for therapeutic activity and 103.3 and 91.2 μg/mL for protective activity, respectively. The dissociation constants (Kd) values of compounds A4 and A23 against TMV-CP were 0.021 and 0.018 μM, respectively, determined by microscale thermophoresis (MST), which were much smaller than those of the commercial drug ningnanmycin (NNM), which were 2.84 μM. The interaction of compounds A4 , A23 with TMV-CP was further verified at the molecular level. In addition, in vitro antifungal assays of this series of compounds showed that they exhibited some inhibitory activity against a variety of fungi, especially against the phytophthora capsici. Among them, A13 and A20 showed similar inhibitory activity to the control drug azoxystrobin at 100 μg/mL against the phytophthora capsici.     

Ontogenetic Variation in Biological Activities of Venoms from Hybrids between Bothrops erythromelas and Bothrops neuwiedi Snakes

Lance-headed snakes are found in Central and South America, and they account for most snakebites in Brazil. The phylogeny of South American pitvipers has been reviewed, and the presence of natural and non-natural hybrids between different species of Bothrops snakes demonstrates that reproductive isolation of several species is still incomplete. The present study aimed to analyze the biological features, particularly the thrombin-like activity, of venoms from hybrids born in captivity, from the mating of a female Bothrops erythromelas and a male Bothrops neuwiedi, two species whose venoms are known to display ontogenetic variation. Proteolytic activity on azocoll and amidolytic activity on N-benzoyl-DL-arginine-p-nitroanilide hydrochloride (BAPNA) were lowest when hybrids were 3 months old, and increased over body growth, reaching values similar to those of the father when hybrids were 12 months old. The clotting activity on plasma diminished as hybrids grew; venoms from 3- and 6-months old hybrids showed low clotting activity on fibrinogen (i.e., thrombin-like activity), like the mother venom, and such activity was detected only when hybrids were older than 1 year of age. Altogether, these results point out that venom features in hybrid snakes are genetically controlled during the ontogenetic development. Despite the presence of the thrombin-like enzyme gene(s) in hybrid snakes, they are silenced during the first six months of life.     

测定6-姜酚标样物质——6-姜酚肟的制取与鉴定

为了获得高纯度的6-姜酚肟,以姜油树脂为原料,通过溶剂萃取、肟化反应和硅胶柱真空层析,获得白色晶体,通过紫外光谱、红外光谱、核磁共振谱、质谱等测定所得白色晶体为6.姜酚肟,并证实了其存在顺反异构.     

Design,Synthesis, Molecular Docking Studies,and Biological Evaluation of Pyrazoline Incorporated Isoxazole Derivatives

Russian Journal of Bioorganic Chemistry - A novel series of pyrazoline incorporated isoxazole derivatives were designed and synthesized. The synthesized compounds were characterized by 1H NMR, IR...     

葡萄种间杂交砧木育种F1代植株耐碱性盐能力分析

我们对以左山一山葡萄(Vitis amurensis cv. ‘Zuoshan1’)为母本、SO4为父本杂交的4个子代株系(A11、A14、A15和A17)及101-1为父本杂交的2个子代株系(B24和B26)的耐碱性盐能力进行评价, 旨在探明杂交砧木在碱性盐胁迫下的生理响应, 筛选出耐碱性盐的株系作为我国盐碱地栽培的候选砧木。实验以砧木1103P及Crimson为对照, 对组培苗炼苗后的盆栽苗进行100 mmol∙L^-1 NaHCO₃ (pH8.62)浇灌处理, 通过主成分分析和相关性分析等方法进行综合评价。结果表明, NaHCO₃胁迫降低了各植株的株高、叶片含水量、植株含水量和根系活力, 增加了叶片电导率、丙二醛含量、可溶性糖与游离脯氨酸含量。A17的株高增长量受影响最小; Crimson、A17和B24植株含水量降低较少; A14和A15的根系活力与对照差异不显著; 1103P、B24、A14、B26、Crimson和A15的相对电导率及B26、A17和A15叶片丙二醛含量与对照无显著差异; A15的叶片可溶性糖及游离脯氨酸含量增加最高。各株系耐碱能力D值分析表明, A14、A15和B24的耐碱性较强, Crimson、A11与A17的耐碱性中等, 1103P和B26的耐碱性较弱。     

Design and Synthesis of Novel Cytotoxic Indole‐Thiosemicarbazone Derivatives: Biological Evaluation and Docking Study

In this work, two novel series of indole‐thiosemicarbazone derivatives were designed, synthesized, and evaluated for their cytotoxic activity against MCF‐7, A‐549, and Hep‐G2 cell lines in comparison to etoposide and colchicine as the reference drugs. Generally, the synthesized compounds showed better cytotoxicity towards A‐549 and Hep‐G2 than MCF‐7. Among them, (2E)‐2‐{[2‐(4‐chlorophenyl)‐1H‐indol‐3‐yl]methylidene}‐N‐(4‐methoxyphenyl)hydrazinecarbothioamide ( 8l ) was found to be the most potent compound against A‐549 and Hep‐G2, at least three times more potent than etoposide. The morphological analysis by the acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that compound 8l induced apoptosis in A‐549 cells. Moreover, molecular docking methodology was exploited to elucidate the details of molecular interactions of the studied compounds with putative targets.     

羟基磷灰石水泥的体外生物学安全性试验

羟基磷灰石水泥(HAC)是新型的羟基磷灰石类人工骨材料。1991年得到美国食品与药物管理局(FDA)的批准,在临床试用,用于颅骨缺损的填充治疗。华东理工大学最近研制出类似的HAC。我们用它的生理盐水浸出液对其进行了生物学安全性试验,包括细胞培养毒性试验、全身注射毒性试验、Ames试验、微核试验及UDS试验。结果表明HAC的浸出液对培养细胞的生长无抑制作用,对体细胞的遗传物质(染色体、DNA)无致突变作用。上述结果提示我们,HAC用于人体是安全的。