共查询到20条相似文献,搜索用时 15 毫秒
1.
Dharam Pal Pathak Vidushi Sharma Sachin Kumar 《Bioorganic & medicinal chemistry letters》2018,28(9):1566-1569
Coumarin containing pyrazoline derivatives have been synthesized and tested as inhibitors of in vitro development of a chloroquine-sensitive (MRC-02) and chloroquine-resistant (RKL-2) strain of Plasmodium falciparum and in vivo Plasmodium berghei malaria. Docking study was also done on cysteine protease falcipain-2 which showed that the binding pose of C-14 molecule and epoxysuccinate, inhibitor of falcipain-2, binds in the similar pattern. The most active antimalarial compound was 3-(1-benzoyl-5-(4-flurophenyl)-4,5-dihydro-1H-pyrazol-3yl)-7-(diethyamino)-2H-chromen-2-one C-14, with an IC50 of 4.21?µg/ml provided complete protection to the infected mice at 24?mg/kg X 4?days respectively. 相似文献
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Sandeep Kumar Marvadi Vagolu Siva Krishna Dharmarajan Sriram Srinivas Kantevari 《Bioorganic & medicinal chemistry letters》2019,29(4):529-533
A series of novel substituted 1,2,3-triazolyldihydroquinolines 6a–o was designed and synthesized from 2-acetylthiophene in five-step reaction sequence involving modified Boltzmann-Rahtz reaction of β-Enaminone; Vilsmeier-Haack chloroformylation using DMF/POCl3; Ohira-Bestmann homologation of aldehyde to alkyne as key steps. The reaction of alkyne 4 with various aryl azides in the presence of copper sulfate and sodium ascorbate resulted desired new 1,2,3-triazolyldihydroquinolines 6a–o in excellent yields. In vitro screening of new compounds for anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv (Mtb), resulted in three derivatives 6a (MIC:1.56?µg/mL) and 6d, 6l (MIC:3.12?µg/mL) as promising antitubercular agents with lower cytotoxicity profiles. 相似文献
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Jurupula Ramprasad Vinay Kumar Sthalam Rama Linga Murthy Thampunuri Supriya Bhukya Ramesh Ummanni Sridhar Balasubramanian Srihari Pabbaraja 《Bioorganic & medicinal chemistry letters》2019,29(20):126671
Towards a quest for establishing new antitubercular agents, we have designed new quinoline–triazole hybrid analogs in a six-step reaction sequence involving versatile reactions like Vilsmeier–Haack and click reaction protocol. The design is based on the structural modification of bedaquiline moiety and involves molecular hybridization approach. The structure of the synthesized product was elucidated by single crystal X-ray diffraction study. The synthesized target compounds were screened for their antitubercular activity against Mycobacterium bovis. Interestingly, two compounds of the series (8d and 8m) showed significant inhibition with MIC of 31.5 and 34.8 μM. Compounds bearing 3-fluoro phenyl and n-octyl groups on the 1,2,3-triazole ring emerged as the most potent leads among the compounds tested. Further these hit compounds were also screened for their cytotoxic effect on human embryonic kindey 293 (HEK293) cells and other cancer cell lines such as HeLa (Cervical), PC3 (Prostate), Panc-1 (Pancreatic) and SKOV3 (Ovarian) indicating to be safer with the minimal cytotoxicity. 相似文献
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Feng Li Qinlong Xu Qihua Zhu Zhaoxing Chu Gaofeng Lin Jiajia Mo Yan Zhao Jiaming Li Guangwei He Yungen Xu 《Bioorganic & medicinal chemistry letters》2019,29(24):126712
To improve the anti-inflammatory activity of desloratadine, we designed and synthesized a series of novel desloratadine derivatives. All compounds were evaluated for their anti-inflammatory and H1 antagonistic activities. Among them, compound 2c showed the strongest H1 antagonistic and anti-inflammatory activity. It also exhibited promising pharmacokinetic profiles and low toxicity. All these results suggest that compound 2c as a novel anti-allergic agent is worthy of further investigation. 相似文献
6.
Rocío Paucar Rubén Martín-Escolano Elsa Moreno-Viguri Amaya Azqueta Nuria Cirauqui Clotilde Marín Manuel Sánchez-Moreno Silvia Pérez-Silanes 《Bioorganic & medicinal chemistry》2019,27(17):3902-3917
The current chemotherapy against Chagas disease is inadequate and insufficient. A series of ten Mannich base-type derivatives have been synthesized to evaluate their in vitro antichagasic activity. After a preliminary screening, compounds 7 and 9 were subjected to in vivo assays in a murine model. Both compounds caused a substantial decrease in parasitemia in the chronic phase, which was an even better result than that of the reference drug benznidazole. In addition, compound 9 also showed better antichagasic activity during the acute phase. Moreover, metabolite excretion, effect on mitochondrial membrane potential and the inhibition of superoxide dismutase (SOD) studies were also performed to identify their possible mechanism of action. Finally, docking studies proposed a binding mode of the Fe-SOD enzyme similar to our previous series, which validated our design strategy. Therefore, the results suggest that these compounds should be considered for further preclinical evaluation as antichagasic agents. 相似文献
7.
Ying Wang Shao-Ru Chen Xiaoming Yang Kuo-Hsiung Lee Yung-Chi Cheng 《Bioorganic & medicinal chemistry》2018,26(3):630-636
The tylophorine analog rac-cryptopleurine exhibited potent anti-hepatitis C virus (HCV) activity through allosteric regulation of ATPase activity of heat shock cognate protein 70 (Hsc70). We evaluated the impact of modifications on the E-ring of rac-cryptopleurine to the inhibitory activity against HCV replication and regulation of ATPase activity of Hsc70. Cryptopleurine analog YXM-110 with a 13α-hydroxyl group maintained activity against HCV and promoted ATP/ADP turnover of Hsc70; however, compounds with hydroxyl groups at other positions or with other orientations (YXM-109, YXM-139, and YXM-140) did not exhibit similar activities. Size modification or heteroatom incorporation of the E-ring led to loss of anti-HCV activity. Promotion of the chaperone activity of Hsc70 with carboxyl terminus Hsc70 interacting protein (CHIP) further enhanced the anti-HCV activity of rac-cryptopleurine and XYM-110. This structure-activity relationship (SAR) study refined structural design and optimization for developing rac-crytopleurine analogs as potent anti-HCV agents targeted against the host factor involved in HCV replication. 相似文献
8.
Mousumi Sarkar Saha Shilpee Pal Indrani Sarkar Ayan Roy Pradeep K. Das Mohapatra Arnab Sen 《Genomics》2019,111(3):426-435
Mycobacterium is gram positive, slow growing, disease causing Actinobacteria. Beside potential pathogenic species, Mycobacterium also contains opportunistic pathogens as well as free living non-pathogenic species. Disease related various analyses on Mycobacterium tuberculosis are very widespread. However, genomic study of overall Mycobacterium species for understanding the selection pressure on genes as well as evolution of the organism is still illusive. MLSA and 16s rDNA based analysis has been generated for 241 Mycobacterium strains and a detailed analysis of codon and amino acid usage bias of mycobacterial genes, their functional analysis have been done. Further the evolutionary features of M. avium complex also have been revealed. Mycobacterial genes are moderately GC rich showed higher expression level in PPs and significant negative correlation with biosynthetic cost of proteins. Translational selection pressure was observed in mycobacterial genes. MAC showed close relationship with NPs and higher evolutionary rate in MAC revealed their constant evolving nature. 相似文献
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Binh Huy Le Han Na Joo Do won Hwang Kyu Wan Kim Young Jun Seo 《Bioorganic & medicinal chemistry letters》2017,27(16):3772-3775
We have developed a AuNP-CTG based probing system that is applicable to the detection of many units of CAG repeat sequences which was synthesized by a rolling circle amplification (RCA) system with changes in fluorescence. We also demonstrate that our AuNP-CTG based probing system could transfect without using transfection reagent and detect target CAG repeat sequences in HeLa cells with dramatic changes in fluorescence. This AuNP-CTG based probing system could also be used, in conjunction with the CAG repeat RCA system, to detect target DNA. This system was so sensitive to the target DNA that it could detect even picomolar amounts with amplification of the fluorescence signal. Furthermore, we have used our gold-based CAG probing system for the detection of RNA CAG repeat sequences. 相似文献
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Yogesh B. Surase Kirandeep Samby Sagar R. Amale Ruchi Sood Kedar P. Purnapatre Pawan K. Pareek Biswajit Das Kamna Nanda Subodh Kumar Ashwani K. Verma 《Bioorganic & medicinal chemistry letters》2017,27(15):3454-3459
A non-diaryl quinoline scaffold 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one was identified by screening of diverse set of compounds against M. smegmatis ATP synthase. Herein, we disclose our efforts to develop the structure activity relationship against Mycobacterium tuberculosis (Mtb.H37Rv strain) around the identified hit 1. A scaffold hopping approach was used to identify compounds 14a, 14b and 24a with improved activity against MTb.H37Rv. 相似文献
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2-Phenylethanol (2-PE) is an important flavor ingredient with a rose-like odor. Due to concerns about the toxic byproducts potentially found in 2-PE from chemical synthesis, consumers prefer the natural aroma compound, promoting the biosynthesis of 2-PE. Various microorganisms produce 2-PE naturally with low yield. Recent metabolic engineering strategies in yeasts and Escherichia coli have achieved great success in improving 2-PE bioproduction, including the alleviation of feed-back inhibition, improvement of precursor transport, enhancing activities of crucial enzymes, and reduction of by-products. Here, we review the metabolic engineering strategies applied to microorganisms for increasing bioproduction of 2-PE, address current problems, and propose further improvements. 相似文献
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Monica Modesto Edoardo Puglisi Andrea Bonetti Samanta Michelini Caterina Spiezio Camillo Sandri Barbara Sgorbati Lorenzo Morelli Paola Mattarelli 《Systematic and applied microbiology》2018,41(6):593-603
Four novel Gram-stain-positive, non spore forming and fructose-6-phosphate phosphoketolase-positive strains were isolated from the faeces of a cotton top tamarin (Saguinus oedipus) and an emperor tamarin (Saguinus imperator). Phylogenetic analyses based on 16S rRNA revealed that bifidobacterial strains TRE 1T exhibit close phylogenetic relatedness to Bifidobacterium catulorum DSM 103154 (96.0%) and Bifidobacterium tissieri DSM 100201 (96.0%); TRE DT and TRE HT were closely related to Bifidobacterium longum subsp. longum ATCC 15708T with similarity values of 97.4% and 97.5%, respectively; TRI 7T was closely related to Bifidobacterium tissieri DSM 100201 (96.0%). The Average Nucleotide Identity (ANI) and in silico DDH (isDDH) analysis with closest neighbour supported an independent phylogenetic position of all strains with values ranged from 74 to 85% for ANI and from 24 to 28% for isDDH. DNA base composition of the four strains was in the range of 58.3–63.5 mol% G + C. Based on the phylogenetic, genotypic and phenotypic data, the strains TRE 1T, TRE DT, TRE HT and TRI 7T clearly represent four novel taxa within the genus Bifidobacterium for which the names Bifidobacterium primatium sp. nov. (type strain TRE 1T = DSM 100687T = JCM 30945T), Bifidobacterium scaligerum sp. nov. (type strain TRE DT = DSM 103140T = JCM 31792T), Bifidobacterium felsineum sp. nov. (type strain TRE HT = DSM 103139T = JCM 31789T) and Bifidobacterium simiarum sp. nov. (type strain TRI 7T = DSM 103153T = JCM 31793) are proposed. 相似文献
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Ehab Salama Ghada Nour Eldeen Mazen Abdel Rasheed Sahar Abdel Atti Amr Elnoury Tamer Taha Osama Azmy 《Journal of Genetic Engineering and Biotechnology》2018,16(1):63-69
Endometriosis is a common chronic gynecological disorder defined as the presence of ectopic functional endometrial tissues, outside uterine cavity, primarily on the pelvic peritoneum and the ovaries. Several studies revealed a correlation between aberrant stem-cell activity in the endometrium and endometriosis. Yet the molecular and cellular behaviors of mesnchymal stem cells in development of endometriosis are hampered by lack of invitro experiments. Our aim was to explore morphological and molecular changes associated with mesenchymal stem cells (MSCs) exposition to serum derived from women with severe endometriosis. Two cell cultures of MSCs isolated from endometrial tissues of two endometriosis-free women. Each cell culture was treated individually with the serum of women with endometriosis (experimental group/n =?7), and serum of women without endometriosis (control group/ n = 4) for 14?days. Quantitative Real-Time PCR was performed later to reveal expression of OCT-4, CDH1 and CDH2, STAT3 and SOX2 genes. Morphologically, cells showed no significant changes. However from molecular point of view, we found increased expression in OCT-4, CDH1 and CDH2. For STAT3 and SOX2 we did not find a significant difference. This study shows that endometriosis serum induced molecular changes in human endometrial MSCs (EnMSCs) that might be related to altered cell behavior which may be a step in differentiation that may be completed invivo by other factors to complete the process of transition. Further researches are needed for optimization to reach differentiation. 相似文献
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Metagenomic analysis of biofilm forming bacteria in environmental samples remains challenging due to the non-availability of gene sequences of most of the uncultivable bacteria. Sequences of Pseudomonas aeruginosa PAO1-UW genes involved either directly or indirectly in biofilm formation were analyzed using BLASTn to obtain matching sequences from different strain, species and genus. Conserved regions in the functional domain of the amino acid sequences were used to design common primers for direct PCR analysis of freshwater metagenomes. Seven key genes such as aceA, clpP, typA, cbrA, phoR, rpoS and gacA involved in biofilm formation were validated. The ortholog genes belonged to wide range of Pseudomonas sp. indicating the diversity of biofilm genes and the conservation of protein functional domains. The approach would also help in analyzing the expression of biofilm genes in different bacteria of freshwater systems for monitoring toxic contaminations such as organic or inorganic pollutants. 相似文献
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Ewan K.S. McRae David E. Davidson Steven J. Dupas Sean A. McKenna 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(9):1973-1979
Guanine quadruplexes can form in both DNA and RNA and influence many biological processes through various protein interactions. The DEAD-box RNA helicase protein DDX21 has been shown to bind and remodel RNA quadruplexes but little is known about its specificity for different quadruplex species. Previous reports have suggested DDX21 may interact with telomeric repeat containing RNA quadruplex (TERRA), an integral component of the telomere that contributes to telomeric heterochromatin formation and telomere length regulation. Here we report that the C-terminus of DDX21 directly interacts with TERRA. We use, for the first time, 2D saturation transfer difference NMR to map the protein binding site on a ribonucleic acid species and show that the quadruplex binding domain of DDX21 interacts primarily with the phosphoribose backbone of quadruplexes. Furthermore, by mutating the 2′OH of loop nucleotides we can drastically reduce DDX21's affinity for quadruplex, indicating that the recognition of quadruplex and specificity for TERRA is mediated by interactions with the 2′OH of loop nucleotides. 相似文献
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Jeeva Susan Abraham S. Sripoorna Jyoti Dagar Shiv Jangra Anit Kumar Khushi Yadav Simran Singh Anusha Goyal Swati Maurya Geetu Gambhir Ravi Toteja Renu Gupta Dileep K. Singh Hamed A. El-Serehy Fahad A. Al-Misned Saleh A. Al-Farraj Khaled A. Al-Rasheid Saleh A. Maodaa Seema Makhija 《Saudi Journal of Biological Sciences》2019,26(6):1305-1313
The present investigation aims to study the diversity of ciliates from different habitats in and around Delhi, India, and the correlation of this diversity with soil quality {agricultural lands (site 1 and 2), dump yards (site 3 and 4), sewage treatment plant (site 5), residential land (site 6), landfill (site 7) and barren land (site 8)}. Various physicochemical parameters of the different soil samples were studied and analysed for soil texture, interstitial water, pH, conductivity, total organic carbon, total organic matter, total nitrogen and phosphorous content, using standard protocols. Seventeen ciliate taxa belonging to four classes, seven orders, ten families, and 17 genera were recorded, with the maximum number of species (eleven) belonging to the class Spirotrichea. Ciliate diversity was highest at sites 5 and 6 and lowest at sites 1 and 2. Spathidium sp. was the dominant species in the conditioned land (site 8), while the ciliate Colpoda sp. was present in all the sites examined, showing the highest population density in the sewage treatment plant site (site 5). Statistical analysis showed that ciliate diversity was positively correlated to physicochemical parameters such as interstitial water, total organic matter and organic carbon, total nitrogen and total phosphorous content. Analyses of spirotrichs/colpodids (S/C) ratio and diversity indices implied that the habitat conditions of sites 1, 2, 3 and 8 are relatively unfavourable for soil ciliates to flourish; while sites 4, 5, 6 and 7 provided more favourable conditions. The ubiquity of ciliate distribution suggests their important role in the soil food webs and nutrient cycling, and their community structure and specific characteristics appear to be of major importance for soil formation. A full understanding of soil ciliate diversity and physicochemical parameters helps to inform best practice for improving soil quality as well as conservation practices for sustainable development and management of farms and cultivated lands. In conclusion, ciliate diversity serves as an important and sensitive bio-indicator for soil quality. 相似文献
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Sophie Winkler Rupert Derler Bernd Gesslbauer Elmar Krieger Andreas J. Kungl 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(3):528-533