Graciela Pinto Vitorino, C. Avila, Rosalía Ayala Gómez, M. Becerra, M. Mazzieri
{"title":"Supramolecular complex of norfloxacin and sulfamethoxazole: Synthesis, characterization, and evaluation of the antibacterial activity","authors":"Graciela Pinto Vitorino, C. Avila, Rosalía Ayala Gómez, M. Becerra, M. Mazzieri","doi":"10.3390/ecmc-4-05614","DOIUrl":"https://doi.org/10.3390/ecmc-4-05614","url":null,"abstract":"","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76321050","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}
M. Nikolic, V. Dobričić, M. Mijajlovic, A. Bukonjic, D. Tomović, G. Radić, Z. Vujić, J. Brborić, O. Čudina
: The aim
:目标
{"title":"Molecular docking studies of novel 9-aminoacridines with potential antimalarial activity","authors":"M. Nikolic, V. Dobričić, M. Mijajlovic, A. Bukonjic, D. Tomović, G. Radić, Z. Vujić, J. Brborić, O. Čudina","doi":"10.3390/ECMC-4-05605","DOIUrl":"https://doi.org/10.3390/ECMC-4-05605","url":null,"abstract":": The aim","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88668931","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}
Nitro compounds show great importance in chemistry, biology and material sciences. Among them, nitropyridines and nitroanilines are widely used as useful intermediates for synthesis of biologically active compounds of pharmaceutical and agrochemical importance. Hence, we reported a powerful method for synthesis of various kinds of nitro compounds by using a three component ring transformation (TCRT) of dinitropyridone 1 with ketones in the presence of less nucleophilic ammonium acetate (NH4OAc) as nitrogen source. When pyridone 1 was reacted with aromatic ketone in the presence of ammonium acetate, 6-arylated 3-nitropyriines 2 were formed besides diazabicyclo compounds 3. This method was also applicable to cycloalkanones and α,β-unsaturated ketones to afford cycloalka[b]pyridines 4 and 6-alkynylated/alkenylated pyridines 5, respectively. It was found to be possible to use aldehydes as the substrate, what led to 3,5-disubstituted pyridines 6. On the other hand, when aliphatic ketones were employed as the substrate, two kinds of ring transformation proceeded. Namely, 2,6-disubstituted 4-nitroanilines 8 were formed in addition to nitropyridines 7. This protocol was successful applied to synthesis of N,N,2,6-tetrasubstituted nitroanilines 9 upon treatment of dinitropyridone 1 with ketone and amine in the presence of acetic acid.
{"title":"An introduction to the synthesis of nitroanilines and nitropyridines via three component ring transformation","authors":"S. Le, N. Nishiwaki","doi":"10.3390/ecmc-4-05616","DOIUrl":"https://doi.org/10.3390/ecmc-4-05616","url":null,"abstract":"Nitro compounds show great importance in chemistry, biology and material sciences. Among them, nitropyridines and nitroanilines are widely used as useful intermediates for synthesis of biologically active compounds of pharmaceutical and agrochemical importance. Hence, we reported a powerful method for synthesis of various kinds of nitro compounds by using a three component ring transformation (TCRT) of dinitropyridone 1 with ketones in the presence of less nucleophilic ammonium acetate (NH4OAc) as nitrogen source.\u0000When pyridone 1 was reacted with aromatic ketone in the presence of ammonium acetate, 6-arylated 3-nitropyriines 2 were formed besides diazabicyclo compounds 3. This method was also applicable to cycloalkanones and α,β-unsaturated ketones to afford cycloalka[b]pyridines 4 and 6-alkynylated/alkenylated pyridines 5, respectively. It was found to be possible to use aldehydes as the substrate, what led to 3,5-disubstituted pyridines 6.\u0000On the other hand, when aliphatic ketones were employed as the substrate, two kinds of ring transformation proceeded. Namely, 2,6-disubstituted 4-nitroanilines 8 were formed in addition to nitropyridines 7. This protocol was successful applied to synthesis of N,N,2,6-tetrasubstituted nitroanilines 9 upon treatment of dinitropyridone 1 with ketone and amine in the presence of acetic acid.","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90203989","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}
Š. Pospíšilová, J. Jampílek, J. Kos, Hana Michnová, Tomas Strharsky, A. Čížek
Despite the fact that the percentage of methicillin-resistant Staphylococcus aureus is slowly decreasing in Europe [1], new compounds for fighting bacterial infections are still needed. Biofilm-associated infections, which are a significant cause of mortality, are also considered a serious problem [2]. Derivatives of cinnamic acid have been investigated for a long time due to their wide spectrum of biological activities, such as antibacterial, antiviral, antidiabetic, anxiolytic and anti-inflammatory [3]. Based on these facts, a series of 16 ring-substituted N-arylcinnamamides was synthetized and investigated for their antibacterial activity against S. aureus ATCC 29213 and 3 methicillin-resistant isolates. The microtitration dilution method was used for the determination of minimum inhibitory concentration (MIC). In addition, the most potent compounds were studied for their synergetic effect with clinically used antibacterial chemotherapeutics and ability to inhibit and degrade staphylococcal biofilm; in addition, the dynamics of their antibacterial activity was characterized. (2E)-N-[3,5-bis(Trifluoromethyl)phenyl]-3-phenylprop-2-enamide and (2E)-3-phenyl-N-[3-(trifluoromethyl)phenyl]prop-2-enamide showed the highest activities (MICs = 22.27 and 27.47 µM, respectively) against all four staphylococcal strains. These compounds showed an activity against biofilm formation of S. aureus ATCC 29213 in concentrations close to MICs, but no degradative effect on mature biofilm was observed. Both compounds showed abilities to increase the activity of clinically used antibiotics with different mechanisms of action (vancomycin, ciprofloxacin and tetracycline). In time-kill studies, a decrease of colony-forming units (CFU/mL) of >99% was observed after 8 h from the beginning of incubation. This contribution was supported by grant No. UK/229/2018 of the Comenius University in Bratislava, grants FaF UK/9/2018 and FaF UK/37/2018 of the Faculty of Pharmacy of Comenius University in Bratislava and partially by SANOFI-AVENTIS Pharma Slovakia, s.r.o. HEUER, O. et al. Antimicrobial resistance surveillance in Europe: annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). European Centre for Disease Prevention and Control (ECDC), 2010. SON, J.S. et al. Antibacterial and biofilm removal activity of a podoviridae Staphylococcus aureus bacteriophage SAP-2 and a derived recombinant cell-wall-degrading enzyme. Microbiol. Biotechnol. 2010. 86, 1439-1449. POSPISILOVA, S. et al. Synthesis and spectrum of biological activities of novel N‑arylcinnamamides. J. Mol. Sci. 2018, 19, 2318.
{"title":"N-Arylcinnamamides as antistaphylococcal agents","authors":"Š. Pospíšilová, J. Jampílek, J. Kos, Hana Michnová, Tomas Strharsky, A. Čížek","doi":"10.3390/ECMC-4-05576","DOIUrl":"https://doi.org/10.3390/ECMC-4-05576","url":null,"abstract":"Despite the fact that the percentage of methicillin-resistant Staphylococcus aureus is slowly decreasing in Europe [1], new compounds for fighting bacterial infections are still needed. Biofilm-associated infections, which are a significant cause of mortality, are also considered a serious problem [2]. Derivatives of cinnamic acid have been investigated for a long time due to their wide spectrum of biological activities, such as antibacterial, antiviral, antidiabetic, anxiolytic and anti-inflammatory [3]. \u0000Based on these facts, a series of 16 ring-substituted N-arylcinnamamides was synthetized and investigated for their antibacterial activity against S. aureus ATCC 29213 and 3 methicillin-resistant isolates. The microtitration dilution method was used for the determination of minimum inhibitory concentration (MIC). In addition, the most potent compounds were studied for their synergetic effect with clinically used antibacterial chemotherapeutics and ability to inhibit and degrade staphylococcal biofilm; in addition, the dynamics of their antibacterial activity was characterized. \u0000(2E)-N-[3,5-bis(Trifluoromethyl)phenyl]-3-phenylprop-2-enamide and (2E)-3-phenyl-N-[3-(trifluoromethyl)phenyl]prop-2-enamide showed the highest activities (MICs = 22.27 and 27.47 µM, respectively) against all four staphylococcal strains. These compounds showed an activity against biofilm formation of S. aureus ATCC 29213 in concentrations close to MICs, but no degradative effect on mature biofilm was observed. Both compounds showed abilities to increase the activity of clinically used antibiotics with different mechanisms of action (vancomycin, ciprofloxacin and tetracycline). In time-kill studies, a decrease of colony-forming units (CFU/mL) of >99% was observed after 8 h from the beginning of incubation. \u0000 \u0000This contribution was supported by grant No. UK/229/2018 of the Comenius University in Bratislava, grants FaF UK/9/2018 and FaF UK/37/2018 of the Faculty of Pharmacy of Comenius University in Bratislava and partially by SANOFI-AVENTIS Pharma Slovakia, s.r.o. \u0000 \u0000 \u0000HEUER, O. et al. Antimicrobial resistance surveillance in Europe: annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). European Centre for Disease Prevention and Control (ECDC), 2010. \u0000SON, J.S. et al. Antibacterial and biofilm removal activity of a podoviridae Staphylococcus aureus bacteriophage SAP-2 and a derived recombinant cell-wall-degrading enzyme. Microbiol. Biotechnol. 2010. 86, 1439-1449. \u0000POSPISILOVA, S. et al. Synthesis and spectrum of biological activities of novel N‑arylcinnamamides. J. Mol. Sci. 2018, 19, 2318.","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"369 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79372274","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}
J. Schneider, B. Pradines, F. Helle, A. Dassonville-Klimpt, N. Taudon, P. Sonnet
Malaria is a neglected tropical disease that remains a leading cause of morbidity and mortality among the world’s poorest populations. In 2015, 91 tropical and sub-tropical countries are endemic for this infectious disease. Pregnant women and children are the most sensitive to this infection and, in 2015, 429 000 people died. Among the five species of Plasmodium responsible for human malaria, P. falciparum is the parasite which causes the most serious form of the disease. More recent efforts focused on the development of antimalarial vaccines and since 2006, World Health Organization (WHO) recommends artemisinin-based combination therapies (ACTs). In drugs resistance areas, several antimalarial drugs, such as aminoaryl-alcohol (mefloquine (MQ), lumefantrine (LM)), are currently used in combination with artemisinin derivatives. However, the emergence of multi-drug-resistant parasites decreases efficacy of ACTs. Thus, the design of new active compounds on Plasmodium-resistant strains is urgently. We have previously developed an asymmetric synthesis to prepare 4-aminoquinoline-methanol enantiomers (AQM) as MQ analogs. They were active on nanomolar range against Pf3D7 (chloroquine-sensitive) and PfW2 (chloroquine-resistant) P. falciparum strains. Interestingly, (S)-enantiomers displayed an activity increased by 2 to 15-fold as compared to their (R)-counterparts. Currently their mechanisms of actions are not totally clear and remain to be explored. In continuation of our work, we are interested now to study the change of heterocycle (fluorene vs quinoline) on the antimalarial activity. We focus on the design and the preparation of novel asymmetric 2,4,7-trisusbtituted fluorenes, new aminofluorene-methanol derivatives (AFM) as LM analogs. The evaluation of their antiplasmodial activities against P. falciparum and their corresponding cytotoxicities proved the interest of this pharmacophore with activities on nanomolar range against Pf3D7 and PfW2. We will present here the access and the biological results on these AFMs.
{"title":"Enantiopure aminoaryl-alcohols with fluorene core to antimalarial activity","authors":"J. Schneider, B. Pradines, F. Helle, A. Dassonville-Klimpt, N. Taudon, P. Sonnet","doi":"10.3390/ecmc-4-05575","DOIUrl":"https://doi.org/10.3390/ecmc-4-05575","url":null,"abstract":"Malaria is a neglected tropical disease that remains a leading cause of morbidity and mortality among the world’s poorest populations. In 2015, 91 tropical and sub-tropical countries are endemic for this infectious disease. Pregnant women and children are the most sensitive to this infection and, in 2015, 429 000 people died. Among the five species of Plasmodium responsible for human malaria, P. falciparum is the parasite which causes the most serious form of the disease. More recent efforts focused on the development of antimalarial vaccines and since 2006, World Health Organization (WHO) recommends artemisinin-based combination therapies (ACTs). In drugs resistance areas, several antimalarial drugs, such as aminoaryl-alcohol (mefloquine (MQ), lumefantrine (LM)), are currently used in combination with artemisinin derivatives. However, the emergence of multi-drug-resistant parasites decreases efficacy of ACTs. Thus, the design of new active compounds on Plasmodium-resistant strains is urgently. \u0000We have previously developed an asymmetric synthesis to prepare 4-aminoquinoline-methanol enantiomers (AQM) as MQ analogs. They were active on nanomolar range against Pf3D7 (chloroquine-sensitive) and PfW2 (chloroquine-resistant) P. falciparum strains. Interestingly, (S)-enantiomers displayed an activity increased by 2 to 15-fold as compared to their (R)-counterparts. Currently their mechanisms of actions are not totally clear and remain to be explored. \u0000In continuation of our work, we are interested now to study the change of heterocycle (fluorene vs quinoline) on the antimalarial activity. We focus on the design and the preparation of novel asymmetric 2,4,7-trisusbtituted fluorenes, new aminofluorene-methanol derivatives (AFM) as LM analogs. The evaluation of their antiplasmodial activities against P. falciparum and their corresponding cytotoxicities proved the interest of this pharmacophore with activities on nanomolar range against Pf3D7 and PfW2. We will present here the access and the biological results on these AFMs.","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82959058","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}
L. Biliavska, Yulia Pankivska, O. Povnitsa, O. Vasyliuk, K. Naumenko, I. Garmasheva, S. Zagorodnya
Introduction: In the current scenario of antiviral research, lactic acid bacteria (LAB) and their derived polymers or polysaccharides are considered potential candidates in antiviral therapy to prevent or treat viral infections in both human and animals with remarkable efficacy and might have significant contribution in medicine and pharmaceutical industries in future. The aim of this work was to study the anti-herpetic activity of exopolysaccharides produced by Leuconostoc sp. Methodology: The strains of the LAB were isolated from fermented homemade vegetables: apples, tomato juice, and sauerkraut. Exopolysaccharides (EPSs) were isolated from the culture fluid. Cytotoxicity and antiherpetic activity of 7 EPSs (15a, 48a, 33a, 43a, 2t, 19s, and 6s) were studied using MTT assay. The influence of EPSs on the herpes simplex virus 1 type (HSV-1) was determined by the virucidal, adsorption and penetration assays. The impact of the EPSs on the cell cycle under a condition of HSV-1 infection was analyzed using flow cytometric analysis of propidium iodide-stained cells. Results: All EPSs demonstrated the minimal cytotoxicity of cells and their CC50 values were >3.5 mg/ml. It was determined, that only EPSs 2t, 19s, and 6s significantly inhibited HSV-1 reproduction; their EC50 value equal to 0.2 and 0.5 mg/ml, and the selectivity index was in the range of 39 – 52. Moreover, their showed virucidal activity when were added to virus 3 h before adsorption reduced HSV-1 infectivity by 86 – 97%. Our studies revealed that these EPSs were able to prevent the HSV-1 attachment to cells and penetration into cells in a different manner, reducing HSV-1 production by 70 – 99 %. Furthermore, the normalization of the number of cells in all phases of the cell cycle compared with the profile of infected cells and the increasing number of cells in G1 phase to 79% compared with the control values of viral infections were determined after using of EPSs. Conclusion: This study presents the first data indicating an enormous potential of using EPSs the genus Leuconostoc sp. for lower or hinder the spread of diseases caused by herpesviruses. Funding: Publications are based on the research provided by the grant support of the State Fund for Fundamental Research (project F83).
{"title":"Antiviral activity of the exopolysaccharides produced by Leuconostoc sp. against HSV-1","authors":"L. Biliavska, Yulia Pankivska, O. Povnitsa, O. Vasyliuk, K. Naumenko, I. Garmasheva, S. Zagorodnya","doi":"10.3390/ECMC-4-05611","DOIUrl":"https://doi.org/10.3390/ECMC-4-05611","url":null,"abstract":"Introduction: In the current scenario of antiviral research, lactic acid bacteria (LAB) and their derived polymers or polysaccharides are considered potential candidates in antiviral therapy to prevent or treat viral infections in both human and animals with remarkable efficacy and might have significant contribution in medicine and pharmaceutical industries in future. The aim of this work was to study the anti-herpetic activity of exopolysaccharides produced by Leuconostoc sp.\u0000Methodology: The strains of the LAB were isolated from fermented homemade vegetables: apples, tomato juice, and sauerkraut. Exopolysaccharides (EPSs) were isolated from the culture fluid. Cytotoxicity and antiherpetic activity of 7 EPSs (15a, 48a, 33a, 43a, 2t, 19s, and 6s) were studied using MTT assay. The influence of EPSs on the herpes simplex virus 1 type (HSV-1) was determined by the virucidal, adsorption and penetration assays. The impact of the EPSs on the cell cycle under a condition of HSV-1 infection was analyzed using flow cytometric analysis of propidium iodide-stained cells.\u0000Results: All EPSs demonstrated the minimal cytotoxicity of cells and their CC50 values were >3.5 mg/ml. It was determined, that only EPSs 2t, 19s, and 6s significantly inhibited HSV-1 reproduction; their EC50 value equal to 0.2 and 0.5 mg/ml, and the selectivity index was in the range of 39 – 52. Moreover, their showed virucidal activity when were added to virus 3 h before adsorption reduced HSV-1 infectivity by 86 – 97%. Our studies revealed that these EPSs were able to prevent the HSV-1 attachment to cells and penetration into cells in a different manner, reducing HSV-1 production by 70 – 99 %. Furthermore, the normalization of the number of cells in all phases of the cell cycle compared with the profile of infected cells and the increasing number of cells in G1 phase to 79% compared with the control values of viral infections were determined after using of EPSs.\u0000Conclusion: This study presents the first data indicating an enormous potential of using EPSs the genus Leuconostoc sp. for lower or hinder the spread of diseases caused by herpesviruses.\u0000Funding: Publications are based on the research provided by the grant support of the State Fund for Fundamental Research (project F83).","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84650659","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}
Current problem in pharmacy is the creation of complex drugs based on Hypericum maculatum L., which have anti-inflammatory, astringent, antispasmodic and tonic effects. Hypericum herb contains a complex of biologically active substances of different polarity: flavonoids, hypericin, tannins, vitamins, carotenoids. Biphasic extraction solvents system allows, by one cycle, to simultaneously obtain two extracts, alcohol and oil, containing a complex of hydrophilic and lipophilic compounds. The dependence of the ratio of the polar and non-polar phases on the biologically active substances extraction from the Hypericum herb was studied. The effectiveness of two-phase extraction was determined by the content of flavonoids in the water-alcohol phases and carotenoids in oil phases. It was determined that a two-phase solvent system extracts a complex of biologically active substances of Hypericum maculatum L. more effectively than a sequential extraction with separate solvents of different polarities. The polar phase enhances the processes of desorption, diffusion and phase transfer of not only hydrophilic, but also lipophilic Hypericum herb substances. The optimal ratio of raw materials: 70% ethanol: oil, which provided the maximum yield of flavonoids and carotenoids from raw materials, was 1:10:10.
{"title":"Factors affecting the efficiency of two-phase extraction of flavonoids and carotenoids from Hypericum maculatum L.","authors":"O. Protunkevych, K. Prysiazhniuk","doi":"10.3390/ecmc-4-05606","DOIUrl":"https://doi.org/10.3390/ecmc-4-05606","url":null,"abstract":"Current problem in pharmacy is the creation of complex drugs based on Hypericum maculatum L., which have anti-inflammatory, astringent, antispasmodic and tonic effects. Hypericum herb contains a complex of biologically active substances of different polarity: flavonoids, hypericin, tannins, vitamins, carotenoids. Biphasic extraction solvents system allows, by one cycle, to simultaneously obtain two extracts, alcohol and oil, containing a complex of hydrophilic and lipophilic compounds. The dependence of the ratio of the polar and non-polar phases on the biologically active substances extraction from the Hypericum herb was studied. The effectiveness of two-phase extraction was determined by the content of flavonoids in the water-alcohol phases and carotenoids in oil phases. It was determined that a two-phase solvent system extracts a complex of biologically active substances of Hypericum maculatum L. more effectively than a sequential extraction with separate solvents of different polarities. The polar phase enhances the processes of desorption, diffusion and phase transfer of not only hydrophilic, but also lipophilic Hypericum herb substances. The optimal ratio of raw materials: 70% ethanol: oil, which provided the maximum yield of flavonoids and carotenoids from raw materials, was 1:10:10.","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"222 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87954885","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}
J. Guillon, François Hallé, Solène Savrimoutou, S. Moreau, D. Caignard, P. Sonnet
The tyrosine-protein kinase Src, also known as proto-oncogene c-Src or simply c-Src, is a non-receptor tyrosine kinase protein that has been shown to be involved in the regulation of important cellular processes including migration, survival and proliferation. In fact, Src activation has been associated with multiple cancers, such as colon, breast, pancreas, lung, or brain (Roskoski, R. Jr. Pharmacol. Res. 2015, 94, 9-25; Creedon, H., et al., Crit. Rev. Oncog. 2012, 17, 145-159). There are only few Src inhibitors in clinical development, therefore, there is an urgent need to identify new low molecular weight therapeutics able to inhibit Src and, thus, to modulate aberrant pathways leading to malignant transformation of cells (Lu, X.L., et al., Curr. Med. Chem. 2012, 19, 1821-1829). Heterocyclic compounds attracted a lot of attention because of their wide spread biological activities. Thus, we have previously reported the synthesis of biological active heterocyclic derivatives based on the reactivity of the amidine moiety of 2-amino-2-oxazolines 2 with bis-electrophiles (Massip, S., et al., Bioorg. Med. Chem. 2006, 14, 2697-2719). https://ibb.co/hzkMnJ In a preliminary screening testing our heterocycles library, we have identified a “hit” (compound 1d) derived from various substituted 6-formyl-oxazolo[3,2-a]pyrimidines as a new Src kinase inhibitor (IC50 = 4 µM). These original oxazolo[3,2-a]pyrimidine derivatives 1a-k were synthesized through a Diels-Alder cycloaddition of alkylidene derivatives of 2-amino-2-oxazoline (compounds 3a-k) with acrolein, as an electron-poor dienophile, a reaction previously described by our group (Guillon, J., et al., Synlett 2002, 8, 1249-1252). Versatility given by this reaction allowed us to access a promising family of diversely substituted 6-formyl-oxazolo[3,2-a]pyrimidines with inhibitory effect on Src kinase. Acknowledgments: This work was supported by a grant from Ligue Contre le Cancer (Gironde, Bordeaux, France).
酪氨酸蛋白激酶Src，也被称为原癌基因c-Src或简称c-Src，是一种非受体酪氨酸激酶蛋白，已被证明参与重要细胞过程的调节，包括迁移、存活和增殖。事实上，Src活化与多种癌症有关，如结肠癌、乳腺癌、胰腺癌、肺癌或脑癌(Roskoski, R. Jr. Pharmacol)。Res. 2015, 94, 9-25;克里登，H.等人，克里特。农业学报，2012,17(1):145-159。临床开发中的Src抑制剂很少，因此，迫切需要找到新的低分子量疗法，能够抑制Src，从而调节导致细胞恶性转化的异常途径(Lu, X.L等，Curr。医学化学，2012,19,1821-1829)。杂环化合物因其广泛的生物活性而备受关注。因此，我们之前已经报道了基于2-氨基-2-恶唑啉2的脒部分与双亲电试剂的反应性合成具有生物活性的杂环衍生物(Massip, S.等人，Bioorg.)。医学化学，2006,14,2697-2719)。https://ibb.co/hzkMnJ在我们的杂环文库的初步筛选测试中，我们已经确定了一个“hit”(化合物1d)，它来源于各种取代的6-甲酰基恶唑[3,2-a]嘧啶，作为一种新的Src激酶抑制剂(IC50 = 4µM)。这些原始的恶唑[3,2-a]嘧啶衍生物1a-k是通过2-氨基-2-恶唑啉的烷基基衍生物(化合物3a-k)与丙烯醛的Diels-Alder环加成合成的，丙烯醛是一种电子贫的亲二酚，该反应之前被我们的团队描述过(Guillon, J.， et al.， Synlett 2002, 8, 1249-1252)。该反应的多功能性使我们能够获得具有抑制Src激酶作用的不同取代的6-甲酰基恶唑[3,2-a]嘧啶家族。致谢:这项工作得到了法国癌症协会(法国波尔多吉伦特)的资助。
{"title":"Synthesis and Evaluation of New 6-formyl-oxazolo[3,2-a]pyrimidine derivatives as Potential Src Kinase Inhibitors","authors":"J. Guillon, François Hallé, Solène Savrimoutou, S. Moreau, D. Caignard, P. Sonnet","doi":"10.3390/ecmc-4-05566","DOIUrl":"https://doi.org/10.3390/ecmc-4-05566","url":null,"abstract":"The tyrosine-protein kinase Src, also known as proto-oncogene c-Src or simply c-Src, is a non-receptor tyrosine kinase protein that has been shown to be involved in the regulation of important cellular processes including migration, survival and proliferation. In fact, Src activation has been associated with multiple cancers, such as colon, breast, pancreas, lung, or brain (Roskoski, R. Jr. Pharmacol. Res. 2015, 94, 9-25; Creedon, H., et al., Crit. Rev. Oncog. 2012, 17, 145-159). There are only few Src inhibitors in clinical development, therefore, there is an urgent need to identify new low molecular weight therapeutics able to inhibit Src and, thus, to modulate aberrant pathways leading to malignant transformation of cells (Lu, X.L., et al., Curr. Med. Chem. 2012, 19, 1821-1829). Heterocyclic compounds attracted a lot of attention because of their wide spread biological activities. Thus, we have previously reported the synthesis of biological active heterocyclic derivatives based on the reactivity of the amidine moiety of 2-amino-2-oxazolines 2 with bis-electrophiles (Massip, S., et al., Bioorg. Med. Chem. 2006, 14, 2697-2719). \u0000https://ibb.co/hzkMnJ \u0000In a preliminary screening testing our heterocycles library, we have identified a “hit” (compound 1d) derived from various substituted 6-formyl-oxazolo[3,2-a]pyrimidines as a new Src kinase inhibitor (IC50 = 4 µM). These original oxazolo[3,2-a]pyrimidine derivatives 1a-k were synthesized through a Diels-Alder cycloaddition of alkylidene derivatives of 2-amino-2-oxazoline (compounds 3a-k) with acrolein, as an electron-poor dienophile, a reaction previously described by our group (Guillon, J., et al., Synlett 2002, 8, 1249-1252). Versatility given by this reaction allowed us to access a promising family of diversely substituted 6-formyl-oxazolo[3,2-a]pyrimidines with inhibitory effect on Src kinase. \u0000Acknowledgments: This work was supported by a grant from Ligue Contre le Cancer (Gironde, Bordeaux, France).","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79171991","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}
A. Berzal-Herranz, C. Romero-Lopez, B. Berzal-Herranz
In addition of the protein coding information viral RNA genomes code functional information in structurally conserved units termed functional RNA domains. These RNA domains play essential roles in the viral cycle. Members of the Flaviviridae family are responsible of important worldwide human diseases (e.g. hepatitis C, dengue, zika, west Nile fever, among others). Their genome consists in a (+) single stranded RNA molecule, which contains numerous highly structurally conserved RNA domains. They represent a good model to study and characterize the functional roles of RNA domains in the regulation of essential viral processes (e.g. translation, replication). Understanding the molecular mechanisms behind their function is essential to understand the viral infective cycle. Interfering with the function of the genomic RNA domains offers a potential means of developing antiviral strategies. Nucleic acids tools and in particular aptamers are good candidates for targeting structural RNA domains. Besides its potential as therapeutics, aptamers also provides an excellent means for investigating the functionality of RNA domains in viral genomes.
{"title":"Targeting the other genetic information coded by the viral RNA genomes","authors":"A. Berzal-Herranz, C. Romero-Lopez, B. Berzal-Herranz","doi":"10.3390/ecmc-4-05577","DOIUrl":"https://doi.org/10.3390/ecmc-4-05577","url":null,"abstract":"In addition of the protein coding information viral RNA genomes code functional information in structurally conserved units termed functional RNA domains. These RNA domains play essential roles in the viral cycle. Members of the Flaviviridae family are responsible of important worldwide human diseases (e.g. hepatitis C, dengue, zika, west Nile fever, among others). Their genome consists in a (+) single stranded RNA molecule, which contains numerous highly structurally conserved RNA domains. They represent a good model to study and characterize the functional roles of RNA domains in the regulation of essential viral processes (e.g. translation, replication). Understanding the molecular mechanisms behind their function is essential to understand the viral infective cycle. Interfering with the function of the genomic RNA domains offers a potential means of developing antiviral strategies. Nucleic acids tools and in particular aptamers are good candidates for targeting structural RNA domains. Besides its potential as therapeutics, aptamers also provides an excellent means for investigating the functionality of RNA domains in viral genomes.","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80842268","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":"Competing interactions of miRNAs and proteins: miR10b, miR335, miR21 in breast cancer","authors":"Rahma Ait Hammou, Y. Kasmi, M. Ennaji","doi":"10.3390/ECMC-4-05592","DOIUrl":"https://doi.org/10.3390/ECMC-4-05592","url":null,"abstract":"","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87057155","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}
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