Proceedings of 5th International Electronic Conference on Medicinal Chemistry最新文献_第6页

Targeting neuroblastoma with a new inhibitor of the TAp73 interaction with MDM2 and mutant p53 一种新的TAp73与MDM2和突变型p53相互作用抑制剂靶向神经母细胞瘤

Proceedings of 5th International Electronic Conference on Medicinal Chemistry Pub Date : 2019-10-30 DOI: 10.3390/ecmc2019-06305

L. Raimundo, E. Sousa, L. Saraíva, S. Gomes, J. Soares, Joana B Loureiro, M. Leão, Helena Ramos, Madalena Monteiro, Juliana Calheiro, N. Nazareth, J. Almeida, Agostinho Lemos, J. Moreira, M. Pinto, P. Chlapek, Renata Veselsk

{"title":"Targeting neuroblastoma with a new inhibitor of the TAp73 interaction with MDM2 and mutant p53","authors":"L. Raimundo, E. Sousa, L. Saraíva, S. Gomes, J. Soares, Joana B Loureiro, M. Leão, Helena Ramos, Madalena Monteiro, Juliana Calheiro, N. Nazareth, J. Almeida, Agostinho Lemos, J. Moreira, M. Pinto, P. Chlapek, Renata Veselsk","doi":"10.3390/ecmc2019-06305","DOIUrl":"https://doi.org/10.3390/ecmc2019-06305","url":null,"abstract":"TAp73 is a key tumour suppressor protein, regulating the transcription of unique and shared p53 target genes with crucial roles in tumorigenesis and therapeutic response. As such, in tumours with impaired p53 signalling, like neuroblastoma (NBL), TAp73 activation represents an encouraging strategy to suppress tumour growth and chemoresistance. In this work, we report a new TAp73-activating agent, the 1-carbaldehyde-3,4-dimethoxyxanthone (LEM2), with potent antitumour activity independent of p53 expression. LEM2 was able to release TAp73 from its interaction with both MDM2 and mutant p53 (mutp53), enhancing TAp73 transcriptional activity, cell cycle arrest, and apoptosis in p53-null and mutp53-expressing tumor cells. By cellular thermal shift assay (CETSA), LEM2 induced thermal stabilization of TAp73α but not of MDM2 or mutp53, suggesting the potential interaction of LEM2 with TAp73α. Interestingly, neither LEM2 alcohol 1-(hydroxymethyl)-3,4-dimethoxy-9H-xanthen-9-one (LEMred) or carboxylic acid 3,4-dimethoxy-9-oxo-9H-xanthene-1-carboxylic acid (LEMox) derivatives were able to inhibit the TAp73-MDM2 interaction supporting that LEM2 biological activity was due to the molecule itself and not to its potential derivatives. Consistently with an activation of the TAp73 pathway, LEM2 also displayed potent antitumour activity against patient-derived NBL cells, both alone and in combination of with doxorubicin and cisplatin. Collectively, besides its relevant contribution to the advance of TAp73 pharmacology, LEM2 may pave the way to improved therapeutic alternatives against NBL. Abstract","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"17 1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130708925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conformational, fluorescence and energy parameters of Interferon α2b under the influence of mono and oligoribonucleotides-based drug 单核苷酸和寡核苷酸类药物对干扰素α2b构象、荧光和能量参数的影响

Proceedings of 5th International Electronic Conference on Medicinal Chemistry Pub Date : 2019-10-30 DOI: 10.3390/ecmc2019-06328

R. Nikolaiev, Yevhenii Stepanenko, Z. Tkachuk

引用次数: 0

Photo-crosslinking of human protein kinase regulatory subunit CK2β for the identification of CK2 binding partners 人蛋白激酶调控亚基CK2β的光交联鉴定CK2结合伙伴

Proceedings of 5th International Electronic Conference on Medicinal Chemistry Pub Date : 2019-10-30 DOI: 10.3390/ecmc2019-06334

A. Nickelsen, J. Jose

{"title":"Photo-crosslinking of human protein kinase regulatory subunit CK2β for the identification of CK2 binding partners","authors":"A. Nickelsen, J. Jose","doi":"10.3390/ecmc2019-06334","DOIUrl":"https://doi.org/10.3390/ecmc2019-06334","url":null,"abstract":"Human protein kinase CK2 is a heterotetrameric Ser/Thr kinase, consisting of two catalytic (CK2α/α’) and two regulatory (CK2β) subunits. CK2 plays a key role in several physiological and pathological processes. Moreover in cancer cells it was shown that CK2 is upregulated [1]. Although the number of more than 300 substrates is still increasing, the regulation of CK2 remains unclear [2]. It is assumed that several proteinprotein interactions are involved in the regulation of CK2. Thereby CK2β modulates the substrate specificity of CK2 and also functions as a docking platform for regulators and substrates. This study aims for the identification of binding partners by photo-crosslinking coupled with mass spectrometry. Therefore the unnatural amino acid p-azidophenylalanine (pAzF) is incorporated into CK2β [3]. Here we report the establishment of the photo-crosslinking procedure with purified CK2β-pAzF with its strongest binding partner CK2α as a proof of principle. The photo-crosslinking product of CK2β-pAzF and CK2α was detected by SDS-PAGE analysis and immunostaining. Furthermore it was shown, that the photocrosslink reaction is specific for interaction partners and is not affected by other proteins. The site directed photo-crosslinking reaction was compared to the common used homo-bifunctional NHS-ester disuccinimidyl suberate (DSS) that crosslinks primary amino groups. References: [1] Tawfic, S. et al.: Histol Histopathol. 2001, 16:573-582. [2] Meggio, F.and Pinna, L.A.: FASEB J. 2003, 17:349-368. [3] Chin, J.W. et al.: J. Am. Chem. Soc. 2002, 124, 9026-9027.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125565454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mass spectrometric diffusion parameters and 3D structural analysis of oligomeric associates of glycylhomopeptides and their complexes of silver(I) ion – a stochastic dynamics approach 甘酰基同肽及其银离子配合物的质谱扩散参数和三维结构分析——随机动力学方法

Proceedings of 5th International Electronic Conference on Medicinal Chemistry Pub Date : 2019-10-30 DOI: 10.3390/ecmc2019-06288

B. Ivanova, M. Spiteller

{"title":"Mass spectrometric diffusion parameters and 3D structural analysis of oligomeric associates of glycylhomopeptides and their complexes of silver(I) ion – a stochastic dynamics approach","authors":"B. Ivanova, M. Spiteller","doi":"10.3390/ecmc2019-06288","DOIUrl":"https://doi.org/10.3390/ecmc2019-06288","url":null,"abstract":"The topic to this study is determination of mass spectrometric diffusion parameters “DSD” of oligomeric associates of glycylhomopeptides and their AgI–complexes according to our “stochastic dynamic” approach and model equations under electrospray ionization condition. The problematic has recently gained attenion thanks to the latter formulas connecting among “DSD” data; the measurable outcome “intensity” of analyte ions; and the experimental parameter “temperature,” respectively. The equations are empirically testable and verifiable. In advancing this innovative view upon which models we will carry out analysis of ions of oligomeric associates of peptides, we should point out that it is crucial to further test our formulas on a larger set of chemical classes and experimental conditions in order to verify their universal applicability to different mass spectrometric ionization methods. Because of, on the concept sketched above the DSD parameters correlate excellent linearly with kinetic parameters of fragment reactions and quantum chemical diffusions according to the Arrhenius’s approximation which reflects the 3D molecular structures of analytes. The most important point regarding our concept is that it extends crucially the capability of the mass spectrometry of multidimentional structural analysis when is applied to high accuracy quantum chemical static and molecular dynamic approaches.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123253478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, synthesis, anti-HIV and antimicrobial study of some 3-(1H-benzo[d][1,2,3]triazol-1-yl)-N-phenylalkylamide derivatives 3-(1h -苯并[d][1,2,3]三唑-1-基)- n -苯烷基酰胺衍生物的设计、合成、抗hiv及抗菌研究

Proceedings of 5th International Electronic Conference on Medicinal Chemistry Pub Date : 2019-10-30 DOI: 10.3390/ecmc2019-06284

Rohit Singh

{"title":"Design, synthesis, anti-HIV and antimicrobial study of some 3-(1H-benzo[d][1,2,3]triazol-1-yl)-N-phenylalkylamide derivatives","authors":"Rohit Singh","doi":"10.3390/ecmc2019-06284","DOIUrl":"https://doi.org/10.3390/ecmc2019-06284","url":null,"abstract":"Objective\u0000In the present study, a series of twenty benzotriazolyl-N-phenylalkylamide derivatives (7a-7j) and (8a-8j) were synthesized, characterized by physicochemical and spectral data (IR, 1H NMR, 13C NMR and mass spectroscopy) and evaluated for their anti-HIV activity with the aim to develop novel substituted benzotriazole derivatives with broad-spectrum chemotherapeutic properties. The synthesized compound have been further evaluated as antibacterial and antifungal activity.\u0000Method\u0000A series of twenty benzotriazolyl-N-phenylalkylamide derivatives were synthesized by reacting substituted anilines (1) with 2-chloroacetyl chloride (2) and 3-chloropropionyl chloride (3) to form intermediate (4a-4j) and (5a-5j). Intermediates further reacted with benzotraizole (6) to form benzotriazolyl-N-alkylamide derivatives (7a-7j) and (8a-8j). The synthesized test compounds (7a-7j) and (8a-8j) were assessed by MTT colorimetric assay on C8166 cells and screened for antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (NCIM 2122), Bacillus subtilis (MTCC 121) and Gram-negative bacteria: Escherichia coli (MTCC118), Pseudomonas aeruginosa (MTCC 647), Salmonella typhi (NCIM 2501), Klebsiella pneumonia (MTCC 3384) and in vitro antifungal activity against Candida albicans (MTCC 227) and Aspergillus niger (NCIM 1056) by two fold broth serial dilution method.\u0000Result- Compounds 7h, 7j, 8i and 8j being the most active showed therapeutic index that were >24.4, 31.1, 30.5 and 51.5 compared to Zidovudine (AZT) having therapeutic index (TI) 514342.6. The test compounds 7h, 7i, 7j, 8h, 8i and 8j exhibited very high activity against all the strains of Gram (+) ve and Gram (-) ve bacteria and antifungal strains.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"353 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122791430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coupling deoxy sugars to polyphenols: Neuroprotection and bioavailability 脱氧糖与多酚的偶联:神经保护和生物利用度

Proceedings of 5th International Electronic Conference on Medicinal Chemistry Pub Date : 2019-10-30 DOI: 10.3390/ecmc2019-06341

Patrícia Calado, C. Dias, A. M. Matos, M. T. Blásquez-Sanchez, Alice Martins, P. Dätwyler, B. Ernst, M. P. Macedo, N. Colabufo, A. Rauter

引用次数: 0

Improving colon cancer therapy with a new promising small-molecule activator of the p53-pathway through disruption of p53-MDM2/MDMX interactions 通过破坏p53-MDM2/MDMX相互作用，用一种新的有前途的p53通路小分子激活剂改善结肠癌治疗

Proceedings of 5th International Electronic Conference on Medicinal Chemistry Pub Date : 2019-10-30 DOI: 10.3390/ecmc2019-06306

L. Raimundo, L. Saraíva, Margarida Espadinha, J. Soares, Joana B Loureiro, Juliana Calheiros, N. Nazareth, J. Almeida, M. Alves, Maria-Soledade Santos

引用次数: 0

Microencapsulation of bioactive leaf extracts of Eucalyptus camaldulensis by freeze drying technology using sodium alginate and sodium carboxymethyl cellulose as coating materials 以海藻酸钠和羧甲基纤维素钠为包衣材料，采用冷冻干燥技术对山梨桉叶活性提取物进行微胶囊化

Proceedings of 5th International Electronic Conference on Medicinal Chemistry Pub Date : 2019-10-30 DOI: 10.3390/ecmc2019-06339

O. Nwabor, S. Voravuthikunchai

{"title":"Microencapsulation of bioactive leaf extracts of Eucalyptus camaldulensis by freeze drying technology using sodium alginate and sodium carboxymethyl cellulose as coating materials","authors":"O. Nwabor, S. Voravuthikunchai","doi":"10.3390/ecmc2019-06339","DOIUrl":"https://doi.org/10.3390/ecmc2019-06339","url":null,"abstract":": Bioactive crude ethanolic extracts of Eucalyptus camaldulensis was encapsulated with alginate – CMC using freeze drying technique. The microcapsules were characterized for particle size, morphology, physicochemical parameters such as solubility, swelling index, and micromeritics properties. FTIR was used to evaluate the interactions of the polymer and the extract. Antioxidant and antimicrobial activities of the microcapsules were also demonstrated. Results revealed and irregular shaped microparticles with mean diameter ranging from 6.7 – 26.6 µm. Zeta potential and polydispersity index ranged from -17.01 – 2.23 mV and 0.344 – 0.489 respectively. Percentage yield and encapsulation efficiency ranged between 70.4 – 81.5 % and 74.2±0.011 – 82.43±0.772 %. In addition, the microcapsules exhibited high swelling index with poor solubility. Antioxidant activity of the microcapsules evaluated using DPPH and ABTS assays increased with increase in the concentration of the extract. Minimum inhibitory and minimum bactericidal concentrations of the microcapsules against gram-positive foodborne pathogens ranged from 0.19 – 3.12 mg/mL and 0.19 – 12.25 mg/mL respectively. Moreover, the microcapsules at concentration of 1 mg/mL did not show cytotoxic effects on human colon cell CaCo-2. Alginate – CMC showed good encapsulation properties that preserved the bioactivity of the extract, thus might be employed for application of natural products in processing systems.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116251323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cyclam-based compounds as a novel class of antibacterial and antitumoral agents 以仙客来为基础的化合物是一类新型的抗菌和抗肿瘤药物

Proceedings of 5th International Electronic Conference on Medicinal Chemistry Pub Date : 2019-10-30 DOI: 10.3390/ecmc2019-06292

Luis G. Alves, Adhan Pilon, Sergi Rodríguez-Calado, J. Portel, O. Ferreira, S. A. Sousa, A. Valente, J. Lorenzo, Elisabete R. Silva, Ana M. Martins, J. Leitão

{"title":"Cyclam-based compounds as a novel class of antibacterial and antitumoral agents","authors":"Luis G. Alves, Adhan Pilon, Sergi Rodríguez-Calado, J. Portel, O. Ferreira, S. A. Sousa, A. Valente, J. Lorenzo, Elisabete R. Silva, Ana M. Martins, J. Leitão","doi":"10.3390/ecmc2019-06292","DOIUrl":"https://doi.org/10.3390/ecmc2019-06292","url":null,"abstract":"Cyclams are macrocyclic polyamines which medical interest was fueled by the therapeutic potential of a bicyclam derivative in HIV infection, inflammatory diseases, cancer and stem-cell mobilization.[1] Taking advantage of the biocompatibility, the high metal chelation stability constants and the possibility of N-functionalization of the cyclam backbone, a variety of compounds have been explored in a wide range of medicinal applications.[2] The use of cyclams and cyclam-based complexes as antimicrobial and antitumoral agents has been described in recent years. In particular, trans-disubstituted cyclam salts revealed to be active antibacterial agents against both Gram-positive and Gram-negative bacteria.[3,4]In the field of anticancer applications, several attempts are being made, mostly with CuII complexes, envisaging their use as 64/67Cu radionuclides.[5] Recently, we found that trans-disubstituted cyclam derivatives and their CuII and FeIII complexes display relevant antitumoral activity against HeLa cancer cell lines.[6] To the best of our knowledge, this is the first report on an iron-cyclam compound tested as anticancer agent. [1] De Clercq, E., Nat. Rev. Drug Discov. 2003, 2, 581–587[2] Liang, X.; Sadler, P. J., Chem. Soc. Rev. 2004, 33, 246-266[3] Yu, M.; Nagalingam, G.; Ellis, S.; Martinez, E.; Sintchenko, V.; Spain, M.; Rutledge, P. J.; Todd, M. H.; Triccas, J. A., J. Med. Chem. 2016, 59, 5917–5921[4] Alves, L. G.; Pinheiro, P. F.; Feliciano, J. R.; Dâmaso, D. P.; Leitao, J. H.; Martins, A. M., Int. J. Antimicrob. Agents 2017, 49, 646-649[5] Cai, Z.; Anderson, C. J., J. Label. Compd. Radiopharm. 2014, 57, 224–230[6] Pilon, A.; Lorenzo, J.; Rodriguez-Calado, S.; Adao, P.; Martins, A. M.; Valente, A.; Alves, L. G., ChemMedChem, 2019, 14, 770-778","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124909048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Screening for PKS-I gene cluster from endophytic actinomycetes residing in Ocmium tenuiflorum (Tulsi) and Azadirachta indica (Neem) 荆芥和印楝内生放线菌pks - 1基因簇的筛选

Proceedings of 5th International Electronic Conference on Medicinal Chemistry Pub Date : 2019-10-30 DOI: 10.3390/ecmc2019-06277

Asma Ilyas, R. Tanvir, A. Sheikh, W. Shehzad

{"title":"Screening for PKS-I gene cluster from endophytic actinomycetes residing in Ocmium tenuiflorum (Tulsi) and Azadirachta indica (Neem)","authors":"Asma Ilyas, R. Tanvir, A. Sheikh, W. Shehzad","doi":"10.3390/ecmc2019-06277","DOIUrl":"https://doi.org/10.3390/ecmc2019-06277","url":null,"abstract":"Polyketide synthases type I (PKS-I) gene cluster is responsible for the synthesis of highly assorted group of secondary metabolites such as antimicrobial and anticancer agents. In our study, screening was carried out using degenerate primers to determine the presence of PKS-I gene cluster in endophytic actinomycetes isolated from two medicinal plants Ocmium teniflorum (Tulsi) and Azadirachta indica (Neem). A total of 28 endophytes that were isolated and identified from our previous study were further confirmed through 16S rRNA gene sequencing to exhibit a 99% similarity with Streptomyces sp. The molecular screening using PCR revealed the presence of PKS- I gene with a product size of 750bps in the isolates, FHK-1, FHK-2, FHK-3, FHK-4, FHK-5, FHK-6, FHK-7, FHK-8, FHK-9, FHK-11, FHK-13, FHK-16, FHK-18, FHK-20, FHK-21, FHK-23, FHK,25 and FHK-28. These isolates were further checked for their antimicrobial potential using their crude extracts. They displayed prominent bioactivity against ATCC pathogens, Escherichia coli, Proteus vulgaris, Rhodococcus equi, Staphylococcus epidermidis, Enterococcus faecalis, and Acinetobacter baumanii. Our study revealed that the endophytes from O. tenuiflorum and A. indica are bioactive and versatile harboring the PKS-I gene cluster.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129909420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0