Proceedings of 5th International Electronic Conference on Medicinal Chemistry最新文献

{"title":"The effect of the caffeine on the binding of haloperidol to human serum albumin","authors":"J. Tomović, Emina Mrkalić, J. Milosavljević, Aleksandar Kočović, Ratomir M. Jelić, Miroslav Sovrlić","doi":"10.3390/ecmc2019-06348","DOIUrl":"https://doi.org/10.3390/ecmc2019-06348","url":null,"abstract":"","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"76 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115529388","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}

{"title":"Screening of antibacterial activity of fucoxanthin","authors":"T. Karpiński, A. Adamczak","doi":"10.3390/ecmc2019-06345","DOIUrl":"https://doi.org/10.3390/ecmc2019-06345","url":null,"abstract":"• INTRODUCTION: Fucoxanthin is an orange-coloured pigment present in brown algae (Phaeophyceae) and diatoms (Bacillariophyceae). This non-provitamin A carotenoid shows various biological activities, including antioxidant, anti-inflammatory, anti-obesity, anti-diabetic, and anticancer properties. Its antimicrobial effect is not sufficiently confirmed. Therefore, the purpose of the present work was to determine the activity of fucoxanthin against clinical strains of 20 species of bacteria.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"19 23","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"113943101","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}

{"title":"GalNAc mimetics: from synthesis to potential inhibitors in Alzheimer’s Disease","authors":"João de Barros, A. Rauter, David Evans, Nicolas Dreyfus, G. Sharman","doi":"10.3390/ecmc2019-06349","DOIUrl":"https://doi.org/10.3390/ecmc2019-06349","url":null,"abstract":": N -acetylgalactosamine(GalNAc) belongs to the group of 2-amino-2-deoxysugars which are found in a wide range of biological structures playing a role in in cell-cell interaction and receptor induced cell signaling. Alzheimer’s disease (AD) is a protein misfolding pathology, causing dementia in over 40 million people worldwide. Cellular prion protein (PrP) has a high-affinity binding with amyloid β (Aβ) oligomers, the most toxic species in Alzheimer’s pathology. It has been demonstrated that O -glycosylated GalNAc, attached to Ser/Thr side chain of PrP via an α -glycosidic linkage, promotes the inhibition of amyloidogenesis in AD. In this context, we have synthesized new GalNAc mimetics, with additional contacts in the GalNAc core structure, to improve the interactions with the prion peptide and to investigate the binding affinity with Aβ 1-42 . The study of the intermolecular interactions of the new chemical structures and Aβ 1-42 oligomers was investigated by NMR methods, namely saturation transfer difference NMR (STD-NMR) and 19 Fluorine NMR (F-NMR) protocols. In this communication, synthetic approaches to the GalNAc mimetics will be presented and interaction results regarding C2 substitution and anomeric heteroatoms, such as O, S and Se with Aβ 1-42 oligomers will be discussed. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 2009; 457:1128-32.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134599139","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}

{"title":"The influence of quercetin on the interaction of haloperidol with human serum albumin","authors":"Aleksandar Kočović, Miroslav Sovrlić, Ratomir M. Jelić, J. Tomović, Anđela Uštević, Emina Mrkalić","doi":"10.3390/ecmc2019-06356","DOIUrl":"https://doi.org/10.3390/ecmc2019-06356","url":null,"abstract":"","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133603898","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}

{"title":"3D Printing for medicinal chemistry in space: Crafting our way to Mars","authors":"C. Tsagkaris, A. Camera, Ana Sofia Monteiro Mota, Maria Lydakaki","doi":"10.3390/ecmc2019-06355","DOIUrl":"https://doi.org/10.3390/ecmc2019-06355","url":null,"abstract":"Three Dimensional Printing (3DP) - defined by ISO as “fabrication of objects through the deposition of a material using a print head, nozzle, or another printer technology” - is an emerging component of Medicinal Chemistry (MC). Space provides a challenging environment where 3DP and MC can offer great services while expanding their borders, with regard to pharmaceutical design and tissue engineering. \u0000The purpose of this presentation is twofold. We first present an overview of existing and emerging applications of the 3DP - MC intersection in Space and we then discuss some debatable aspects from a legal point of view. \u0000This is a literature study. We searched biomedical (Pubmed, Google Scholar) and tech – oriented (InTech) databases with key words (3D Printing, Medicinal Chemistry, Space). Moreover we searched the official websites and depositories of national or international Space Agencies. \u00003DP equipment has recently been installed in the International Space Station marking a revolution in Space Research. 3DP in Space has been a synonym to Additive Manufacturing (AM). Astronauts will soon be able to print medication, instead of receiving it from Earth, or even grow tissues such as skin grafts in case of injuries. Clinical trials or pharmaceutical design experiments may be also carried out in microgravity environment. Last but not least, 3DP mediated MC research in Space investigate the recycling of previously used materials or even debris in pharmaceutical design and bioengineering. \u0000In the future 3DP is expected to play a crucial role in Space Exploration. Long term missions or even colonization of the Moon or Mars will not be possible unless the astronauts are able to produce medication, experimental kits and biomaterials among others on their own. The repercussions of such a 3DP - MC coalition are also expected to have an impact on Earth. Remote healthcare facilities, single laboratories and pharmacists and potentially any trained individual will be able to produce medication and biomaterials. Such a potential hides a considerable amount of controversy. Liability and safety issues, patent obtaining procedures and transferability of Space 3DP - MC research findings to Earth consist of emerging concepts in the field of Space Jurisdiction.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"97 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127728254","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}

{"title":"Antiviral activity of fluorinated compounds against DNA- and RNA-containing viruses","authors":"K. Naumenko, Polina A. Zaremba, S. Zagorodnya, Yurii Shermolovych","doi":"10.3390/ecmc2019-06353","DOIUrl":"https://doi.org/10.3390/ecmc2019-06353","url":null,"abstract":"Viral infections occupy an important in human as one of the most common and poorly controlled infections. At present, Influenza A virus (IAV) and Epstein-Barr virus (EBV) cause different infections, thereby imposing a huge toll on both human health and the economy worldwide. Therefore, screening new effective drugs is an urgent and important problem. Our study aimed to determine cytotoxicity and antiviral effect of fluorinated compounds against the Influenza A virus and Epstein-Barr virus. The cytotoxicity was studied in two cell lines by MTT assay. The cytotoxicity of the compounds the rate was 41 – 990 μg/ml in the B95-8 cell culture, which produces EBV, and 200 – 478 μg/ml in MDCK cells. Compounds 10S-47 and 10S-49 were able to inhibit reproduction of IAV with EC 50 of 38 μg/ml and 50 μg/ml, respectively. It was shown that fluorinated compounds showed low effectiveness against the Epstein-Barr virus, and inhibited the reproduction of the virus at 20% in the concentration range of 1 – 100 μg/ml. Also, we studied the potency of compound 10S-47 to make an apoptosis induction because it exhibited a significant cytotoxic effect on the growth of transformed cells. It was established that for compound 10S-47 at 40 mg/ml, the percentage of apoptotic cells exceeded the control and was 10%. The cytotoxicity of compounds was determined by MTT-method, CC 50 were in the range 41 – 990 µg/ml. The antiviral activity of the compounds was determined by RT-PCR. It was shown that only 10S-48 and 10S-49 compounds inhibit EBV reproduction, percentage of inhibition of synthesis of viral DNA was in range from 1 to 7. This data do not allow us to assign this class of compounds to promising anti-EBV agents.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"2009 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116944490","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}

{"title":"Enhancing anticancer activity of spiropyrazoline oxindoles by disrupting p53-MDMs PPIs","authors":"Elizabeth A. Lopes, Margarida Espadinha, M. Mori, M. Botta, Maria J. Santos","doi":"10.3390/ecmc2019-06352","DOIUrl":"https://doi.org/10.3390/ecmc2019-06352","url":null,"abstract":"Cancer is a major public health problem worldwide with 18.1 million new cases of cancer and 9.6 million deaths worldwide in 20181. \u0000The protein p53 is involved in many biological processes that are important to maintain the normal function of the cells (e.g. apoptosis, cell arrest, and DNA repair). It is an attractive target in oncology because it can modulate several additional cellular processes that are relevant for the suppression of tumour development, such as opposing oncogenic metabolic reprogramming, activating autophagy, and restraining invasion and metastasis. In all types of human cancers, the p53 tumour suppressor function is inactivated by mutation or gene deletion or by negative regulators such as MDM2 and MDMX. In the last years, the most popular approach among medicinal chemists to activate the wild-type p53 was the inhibition of p53-MDM2 protein-protein interaction (PPI) using small molecules. However, it is currently known that the full reactivation of p53 is only achieved when the interactions of p53 with both negative regulators are inhibited. Due to the lack of dual p53-MDM2/X PPIs inhibitors in clinical trials, it is urgent to develop small molecules that inhibit p53-MDMs PPIs2. \u0000Our research team has been working on the development and optimization of spiropyrazoline oxindoles to obtain dual p53-MDM2/X PPIs inhibitors. Hence, we have already developed derivatives with good antiproliferative activities in HCT-116 p53(+/+) human colorectal carcinoma cell line, which induce apoptosis and cell cycle arrest at G0/G1 phase, upregulate p53 steady-state levels, and lead to a decrease of MDM2 levels3. In this communication, we report the structure-based computational optimization of this chemical family for the development of novel p53-MDM2/X interactions inhibitors. Our studies will shed light on the possible binding mode of spirooxindole derivatives to MDM2 and MDMX and will drive the hit-to-lead optimization strategy. Furthermore, we report our most recent optimization of the synthesis of these new spiropyrazoline oxindoles derivatives and the first preliminary biological results. \u0000Acknowledgements: This work was supported by National Funds (FCT/MEC, Fundacao para a Ciencia e Tecnologia and Ministerio da Educacao e Ciencia) through UID/DTP/04138/2019 (iMed.ULisboa), project PTDC/QUI-QOR/29664/2017, Principal Investigator grant CEECIND/01772/2017 (M. M. M. Santos) and PhD fellowships SFRH/BD/137544/2018 (E.A. Lopes) and SFRH/BD/117931/2016 (M. Espadinha). \u0000 \u00001Ferlay, J., Colombet, M., Soerjomataram, I., Mathers, C., Parkin, D., Pineros, M., Znaor, A. and Bray, F., Int. J. Cancer, 2019, 144, 1941-1953. \u00002Espadinha M., Barcherini V., Lopes E. A., Santos M. M. M., Curr. Top. Med. Chem. 2018, 18, 647-660. \u00003a) Nunes R., Ribeiro C. J. A., Monteiro Â., Rodrigues C. M. P., Amaral J. D., Santos M. M. M., Eur. J. Med. Chem., 2017, 139, 168-179. b) Amaral J. D., Silva D., Rodrigues C. M. P., Sola S., Santos M. M. M., Front. Chem., 2019, 7, ","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"53 4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123002694","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}

{"title":"Disclosing the effect of doxorubicin and mitoxantrone on cardiac mitochondrial proteome: an in vivo approach using a murine model","authors":"S. R. Brandão, Ana Reis-Mendes, F. Carvalho, M. Bastos, R. Ferreira, V. Costa","doi":"10.3390/ecmc2019-06350","DOIUrl":"https://doi.org/10.3390/ecmc2019-06350","url":null,"abstract":"The number of cancer survivors has increased considerably due to the current therapies. Nevertheless, the cardiac side effects in these patients are still a concern. Our goal was to study the effects of doxorubicin (DOX) and mitoxantrone (MTX) on the molecular mechanisms harbored in the heart of male mice. Six intraperitoneal administrations were given to the animals. DOX- and MTX-treated animals received a total cumulative dose of 9 and 6 mg/kg, respectively. Whole cardiac tissue and corresponding enriched mitochondrial fractions were analyzed by immunoblot and enzymatic techniques. Additionally, enriched mitochondrial fractions were studied by mass spectrometry-based proteomics. From this analysis 693 different proteins were identified, assigned to the biological processes “small molecule metabolic process”, “oxidation -reduction process” and “carboxylic acid metabolic process” . The distribution analysis of the mitochondrial proteome data showed clustering among the conditions. Indeed, MTX treatment presented less similarities with control. Moreover, DOX and MTX promoted a decrease on mitochondrial density. Metabolic adaptations were noticed, more evident for DOX. Concomitantly, metabolic adaptations were noticed, more evident in the heart of DOX treated mice. Indeed, increased GAPDH-to-ATP and ETFDH-to-ATP ratios were observed. Thus, more than differences in cardiac mitochondrial proteome, these drugs seem to decrease this organelle density. Our goal to study the effects of DOX and MTX on the cardiac mitochondrial proteome remodeling of adult male CD-1 mice. GeLC-MS/MS: combines one dimensional SDS-PAGE with liquid chromatography-tandem mass spectrometry Statistical analysis was performed with GraphPad Prism (version 6.0.1). Experimental groups were compared using ordinary one-way ANOVA followed by Turkey’s multiple comparisons test ( p < 0.05). Results are presented as significantly increased ( ), decreased ( ) or no significantly different ( ) related to the control group. Results are presented as significantly increased ( ), decreased ( ) or no significantly different ( ) related to the control group. increased GAPDH/ATP-B ETFDH/ATP-B ratios compared Results are presented as significantly increased ( ), decreased ( ) or no significantly different ( ) related to the control group.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132528118","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}

{"title":"Anticancer activity of the seaweed compound fucoxanthin in breast cancer cell lines cultured as 2D and 3D models","authors":"Ana Catarina Macedo, F. Malhão, Eduardo Rocha, A. Ramos","doi":"10.3390/ecmc2019-06346","DOIUrl":"https://doi.org/10.3390/ecmc2019-06346","url":null,"abstract":"","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"189 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122467215","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}

{"title":"3D Printing in Medicinal Chemistry: Applications, Prospective and Consideration","authors":"C. Tsagkaris, E. Petropoulou, N. Sevdalis, Aggeliki Vakka","doi":"10.3390/ECMC2019-06354","DOIUrl":"https://doi.org/10.3390/ECMC2019-06354","url":null,"abstract":"Three Dimensional Printing (3D Printing) has been defined by ISO as “fabrication of objects through the deposition of a material using a print head, nozzle, or another printer technology”. 3D Printing has been trending in various disciplines from Science to Industry and Art. Being a tool of high precision and flexibility 3D Printing has been both recognized and challenged in the field of Medicinal Chemistry (MC). \u0000The purpose of this poster is to provide an overview of the current and prospective applications and of the debatable aspects of the intersection between 3D Printing and MC. \u0000This is a literature study. We have searched biomedical (Pubmed, Google Scholar) and tech – oriented (InTech) databases with key words (3D Printing, Medicinal Chemistry, considerations). We included studies authored in English or Greek and excluded studies declaring considerable conflict of interest. \u0000The concept 3D Printing has appeared back in 1984. It took about ten years to print the first 3D Printed placebo tablet through the DOS method. In the next two decades 3D Printing related research has focused on tissue engineering. Nonetheless after 2010 various novelties have been developed enabling manufacturers to produce non-placebo drugs in a wealth of forms including tablets (orodispersable, floating, multicompartment etc), insulin and implants. 3D Printing can be categorized under three major variants; Powder solidification, Liquid solidification and Extrusion based systems. \u0000It has been widely accepted that 3D Printing has the potential to revolutionize MC in terms of research and fabrication. Clinical trials can be considerably speeded up grace to the modifying properties of 3D Printing in pair with organ-in-a-chip technologies. Moreover pharmaceutical industry may be greatly altered given that 3D Printing will gradually enable single laboratories, pharmacists and potentially any trained individual to produce medication. The legibility of 3D Printing mediated clinical trials and the accessibility of 3D Printers are potential sources of controversy from a legal point of view.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"80 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131759562","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}