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

{"title":"In vitro Screening of alcoholic and hydroalcoholic extracts of Ayurvedic medicinal plants for the management of hyperlipidemia","authors":"K. Shanker, Pooja Gaur","doi":"10.3390/ecmc2019-06409","DOIUrl":"https://doi.org/10.3390/ecmc2019-06409","url":null,"abstract":"Background: In Ayurveda, obesity is regarded as ‘Medoroga’, a disorder of lipid metabolism. Hyperlipidemia is one of the causes of Obesity. It is a condition when abnormally high levels of lipids (fatty substances) are found in the blood. Aim: The objective of the present study is to explore pancreatic lipase inhibitory activity of plants used in Indian system of medicine i.e. Ayurveda. Method: In the present study, thirty one ‘Lekhenya’ plants were selected from the Ayurveda. Air-dried and finely powdered 31 plant material (2.0 g) were extracted with ethanol and hydro-alcohol (50:50; v/v) (3 × 10 ml) using cold percolation. The inhibition of pancreatic lipase activity of different plant extracts and orlistat (positive control) measured ‘in-vitro’ lipase activity using the spectrophotometric assay. Results : In-vitro lipase inhibition assay showed that six plants are Sterosperum servolides (Roxb.) D.C, Prunus cerasoides D. Don, Murraya koenigii L., Putranjiva roxburghii Wall., Andrographis paniculata (Burm. f.) Wall. ex Nees, Ocimum scantum linn exhibit IC50 value less than 100 (μg/ml) lipase inhibition activity. Conclusion: The study indicates lipase inhibition potential of Ayurvedic plants, may be useful for the management of obesity which correlate with ethanopharmacological data on the use of these plants in Indian traditional medicines.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"118 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123222697","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":"Assessment of chemical composition and antidiabetic potential of Putranjiva roxburghii twigs","authors":"K. Shanker, Sonal Mishra, D. U. Bawankule","doi":"10.3390/ecmc2019-06407","DOIUrl":"https://doi.org/10.3390/ecmc2019-06407","url":null,"abstract":"","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"2009 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125601372","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":"Abietane Diterpenoids from Plectranthus spp. as a potential new class of Protein Kinase C Modulators","authors":"P. Rijo","doi":"10.3390/ecmc2019-06405","DOIUrl":"https://doi.org/10.3390/ecmc2019-06405","url":null,"abstract":"Cancer is one of the highest causes of death worldwide. Protein kinase C (PKC) is a family of kinases divided into three groups according to their regulatory domain structure and cofactors requirement for activation: classical, novel, and atypical PKCs. Recently, PKC family isoforms have been the focus of intense research, and recognized as therapeutic targets in anticancer drug development [1]. Diterpenoids are commonly found in the Plectranthus spp., and have a widespread spectrum of biological activity, namely anticancer properties [2]. The diterpenoid 7α-acetoxy-6β-hydroxyroyleanone (AHR) isolated from P. grandidentatus displays low cytotoxicity and the basic requirements approaches for the development of pharmaceutical formulations based on AHR as a lead. These AHR features includes an extraction optimization and structural and thermal properties characterization [3]. These features suggests that AHR can be used as a lead for drug development. Considering this, a small library of abietane derivatives was tested for their ability to activate PKC isoforms from classical (alpha, α; beta, β), novel (delta, d; epsilon, e) and atypical (zeta, z) subfamilies, using a previously developed yeast-based screening assay to search for modulators of PKC isoforms [4]. The results obtained revealed potent activators of PKC family proteins, namely: a selective activator of PKCd, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz). The patented diterpenoid RoyBz was prepared using AHR as starting material. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCd-dependent mitochondrial apoptotic pathway involving caspase-3 activation. The results indicate that Roy-Bz targets drug resistant cancer stem cells, in HCT116 colon cancer cells, preventing tumor dissemination and recurrence. Moreover, these findings support a tumor suppressive function of PKCd in colon cancer. Overall, these results point to promising activators of PKCs with high potency and isoform-selectivity that may emerge from the exploitation of this new family of abietane diterpenoids [5]. Molecular docking studies are currently ongoing to further identify new selective abietane diterpenoids as new PKC modulators.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126997235","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":"Nanotechnology mediated bee venom: Applications in rheumatoid arthritis","authors":"Lydia L. Smith, Sayantani Das","doi":"10.3390/ecmc2019-06401","DOIUrl":"https://doi.org/10.3390/ecmc2019-06401","url":null,"abstract":"Bee venom has made medicinal progress, specifically, with the Human Immunodeficiency Virus (HIV) and cancer treatment. However, in spite of this therapy being rooted in the treatment of inflammatory disease, bee venom has made little progress in treating Rheumatoid Arthritis (RA). This substance is both simple and complex in chemical structure, and a few significant obstacles are limiting the effectiveness of the venom in arthritic patients. Primarily, the non-specific cytotoxicity of the venom can negatively affect the surrounding cells of the target, and the known degradation of bee venom, before it reaches the target cells, reduces the potency. One promising way to circumvent these issues would be through nanotechnology. Nanoparticles have a high surface area and, in conjunction with proper functionalization, can be used to derive the Melittin and other beneficial components of bee venom into an effective treatment for Rheumatoid Arthritis. The primary goal of this work is to study contemporary nanoparticles used in drug delivery and do a comparative study on the bee venom and the nanoparticles, helping to develop bee venom into a viable clinical treatment for Rheumatoid Arthritis. Graphical Abstract","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"93 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128683613","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":"Tryptophanol-derived oxazoloisoindolinones: Novel small molecule p53 activators with promising antitumor activity","authors":"Maria J. Santos, Valentina Barcherini, S. Gomes, Margarida Espadinha, J. Soares, L. Raimundo, C. Gomes, F. Reis, A. Antunes, L. Saraíva","doi":"10.3390/ecmc2019-06403","DOIUrl":"https://doi.org/10.3390/ecmc2019-06403","url":null,"abstract":"The tumour suppressor p53 is a pivotal target in cancer therapy as this protein is inactive in all human cancers. In the last years, our research group has been working on the design and synthesis of novel small molecules that are able to reactivate p53.[1] Of these, novel scaffolds containing the oxazoloisoindolinone moiety in their chemical structure emerged with very promising anti-cancer properties.[2] In this communication an overview about the therapeutic potential of a tryptophanol-derived oxazoloisoindolinone chemical library as selective p53 activators will be given. Based on the hit tryptophanol-derived small molecule SLMP53-1, identified as a wild-type and mutant p53 reactivator, a second series of compounds was prepared leading to DIMP53-1 (a p53-MDM2/X interactions dual inhibitor) and to SLMP53-2 (small molecule able to restore the wild-type function of mut p53Y220C). The tryptophanol-derived oxazoloisoindolinone chemical family was prepared by a stereoselective cyclocondensation reaction of enantiopure aminoalcohol tryptophanol with several commercially available oxoacids. From the screening of this library, several very promising molecules emerged with potent anticancer activity against aggressive cancers. The anticancer activity and mechanism of action of the target molecules was studied in human colon adenocarcinoma HCT116 cells with wild-type p53 (HCT116 p53+/+) and the corresponding p53-null isogenic derivative cells (HCT116 p53-/-), as well as in several cancer cell lines with different p53 status. The most promising molecules were also evaluated in vivo. \u0000REFERENCES: 1. a) J. D. Amaral et al. Chem. 2019, 7, 15; b) L. Raimundo et al. British J. Pharmacol. 2018, 175, 3947; c) R. C. Nunes et al. Eur. J. Med. Chem. 2017, 139, 168. 2. a) S. Gomes et al., Cancers 2019, 11, 1151; b) J. Soares et al. Mol. Oncol. 2017; 11; 612; c) J. Soares et al. Oncotarget 2016, 7, 4326; d) J. Soares et al. Eur. J. Pharm. Sci. 2015, 66, 138. \u0000ACKNOWLEDGMENTS: We thank PT national funds (FCT/MCTES, Fundacao para a Ciencia e Tecnologia and Ministerio da Ciencia, Tecnologia e Ensino Superior) the funding through grants PTDC/QUI-QOR/29664/2017, UID/DTP/04138/2019 (iMed.ULisboa), UID/QUI/00100/2019 (CQE) and UID/QUI/50006/2019, the principal investigator grants CEECIND/02001/2017 (A. M. M. Antunes) and CEECIND/01772/2017 (M. M. M. Santos), and the PhD fellowships PD/BD/143126/2019 (V. Barcherini), SFRH/BD/96189/2013 (S. Gomes) and SFRH/BD/117931/2016 (M. Espadinha).","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129002583","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":"Effects of chronic Tamoxifen treatment in the hypothalamic circuitry that regulates female sexual behaviour","authors":"C. Pinto, B. Fonseca, S. Sá","doi":"10.3390/ecmc2019-06404","DOIUrl":"https://doi.org/10.3390/ecmc2019-06404","url":null,"abstract":"","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"66 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124192293","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":"Stories from Staudinger: Synthesis of chiral beta-lactams","authors":"Eavan C. McLoughlin, Niamh M. O’Boyle, M. Meegan","doi":"10.3390/ecmc2019-06402","DOIUrl":"https://doi.org/10.3390/ecmc2019-06402","url":null,"abstract":"Combretastatin A-4 (CA-4) is the most potent antimitotic agent of the Combretastatin A series; a group of diaryl stilbenes isolated from the wood of the South African tree Combretum caffrum. [i] It has significant anticancer activity through inhibition of tubulin polymerization and microtubule assembly. [ii] While cis-stilbene structures demonstrate superior biological activity[iii], the corresponding trans derivatives are inherently more stable. Isomerization of cis CA-4 to the trans form is observed both during storage and in vivo during metabolism which dramatically reduces antitumour activity. [iv] Our group has previously employed the Staudinger reaction to synthesize novel 3-hydroxy-1,4-diaryl-2-azetidinones. The problem of CA-4’s Cis- Trans isomerization has been overcome via chemical manipulation of CA-4’s alkene bridge; utilizing a beta-lactam ring to induce cis restriction. A number of analogues have shown potent nanomolar antiproliferative activity in MCF-7 and HL-60 cells with enhanced activity relative to CA-4. [v] Typical Staudinger reactions form mixtures of cis and trans isomers depending on reaction conditions employed, and additionally; at the 3-hydroxy position’s chiral center; racemic mixtures of R&S enantiomers. Trans isomers of 3-substituted-2-azetidinones have been shown to be up to 50 times more potent than the corresponding cis derivatives[vi] emphasizing the requirement to optimize the Staudinger approach to minimize yields of the undesirable cis isomer. Levo- and dextro-rotatory enantiomers hold potential to display lesser or greater biological activity relative to one another.\u0000Our current work aims to:\u0000\u0000Improve the available yield for chiral resolution by determining the necessary conditions to achieve stereoselective synthesis of trans 3-hydroxy-1,4-diaryl-2-azetidinones in the Staudinger reaction;\u0000Purification of racemic mixtures using N-(tert-butoxycarbonyl)-L-Proline as a chiral resolving agent to afford optically pure enantiomers for further biological evaluation.\u0000\u0000Trans 3-hydroxy b-lactams have been separated from cis derivatives using chromatographic purification. We have since optimized the Staudinger reaction to return relative yields of 95:% relative ratio of trans: cis isomers; as indicated by integration of protons at position 3 and 4 of the beta-lactam on 1 H-NMR. Diastereomeric resolution using flash column chromatography followed by hydrolysis of chiral resolving agents has successfully yielded enantiomers of EMCL001&2. Preliminary biochemical data for the enantiomers in breast cancer cells will be reported.\u0000References\u0000[i] Watt, J. M.; Gerdina, M., The Medicinal and Poisonous Plants of Southern and Eastern Africa. E. & S. Livingstone Ltd: Edinburgh and London, U.K., 1962.\u0000[ii] Pettit, G. R.; Singh, S. B.; Hamel, E.; Lin, C. M.; Alberts, D. S.; Garcia-Kendall, D., Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin Experientia 1988, (45).\u0000[iii] Pettit, G. R.; Singh, S. B","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122164987","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":"Development of the model of in silico design of AMPs active against Staphylococcus aureus 25923","authors":"B. Vishnepolsky, M. Pirtskhalava, G. Zaalishvili, M. Karapetian, A. Gabrielian, A. Rosenthal, D. Hurt, Michael Tartakovsky, M. Grigolava","doi":"10.3390/ecmc2019-06359","DOIUrl":"https://doi.org/10.3390/ecmc2019-06359","url":null,"abstract":"","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128529439","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":"Synthesis of N-acetyl and N-formyl pyrazoline derivatives from vanillin and their antigenotoxic activity","authors":"Jovana Muskinja, S. Matić, S. Stanić, Z. Ratković","doi":"10.3390/ecmc2019-06358","DOIUrl":"https://doi.org/10.3390/ecmc2019-06358","url":null,"abstract":": Vanillin is one of the most important natural products, used as a starting material in the new drug design procedures. Starting from vanillin, we can prepare different chalcones, which are known for their pronounced pharmacological and biological activities. For this reason some chalcone analogues have been synthesized from the corresponding vanillin derivatives. Further reaction with hydrazine in formic acid or acetic acid yielded 20 new pyrazoline compounds with N -formyl and N -acetyl groups, respectively. All new compounds were well characterized by IR, 1 H and 13 C NMR spectroscopy and physical data. In vitro DNA protective potential of selected compounds on hydroxyl and peroxyl radical-induced DNA damage was investigated. The results showed that the new synthesized compounds had expressed potential to prevent DNA damage.","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125430349","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":"Effects of Doxorubicin and Mitoxantrone in the brain of differently aged mice: in vivo chemobrain study","authors":"A. Dias-Carvalho, Ana Reis-Mendes, M. Duarte-Araújo, F. Carvalho, M. Bastos, S. Sá, J. Capela, V. M. Costa","doi":"10.3390/ecmc2019-06364","DOIUrl":"https://doi.org/10.3390/ecmc2019-06364","url":null,"abstract":"","PeriodicalId":312909,"journal":{"name":"Proceedings of 5th International Electronic Conference on Medicinal Chemistry","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126513208","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}