Antiviral Chemistry and Chemotherapy最新文献

{"title":"Memantine treatment reduces the incidence of flaccid paralysis in a zika virus mouse model of temporary paralysis with similarities to Guillain-Barré syndrome.","authors":"Venkatraman Siddharthan,&nbsp;Hong Wang,&nbsp;Alexandre Lr de Oliveira,&nbsp;Xin Dai,&nbsp;John D Morrey","doi":"10.1177/2040206620950143","DOIUrl":"https://doi.org/10.1177/2040206620950143","url":null,"abstract":"<p><p>Clinical evidence suggests that Zika virus contributes to Guillain-Barré syndrome that causes temporary paralysis. We utilized a recently described Zika virus mouse model of temporary flaccid paralysis to address the hypothesis that treatment with an <i>N</i>-methyl-D-aspartate receptor antagonist, memantine, can reduce the incidence of paralysis. Aged interferon alpha/beta-receptor knockout mice were used because of their sublethal susceptibility to Zika virus infection. Fifteen to twenty-five percent of mice infected with a Puerto Rico strain of Zika virus develop acute flaccid paralysis beginning at days 8-9 and peaked at days 10-12. Mice recover from paralysis within a week of onset. In two independent studies, twice daily oral administration of memantine at 60 mg/kg/day on days 4 through 9 after viral challenge significantly reduced the incidence of paralysis. No efficacy was observed with treatments from days 9 through 12. Memantine treatment in cell culture or mice did not affect viral titers. These data indicate that early treatment of memantine before onset of paralysis is efficacious, but treatments beyond the onset of paralysis were not efficacious. The effect of this N-methyl-D-aspartate receptor antagonist on the incidence of Zika virus-induced paralysis may provide guidance for investigations on the mechanism of paralysis.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"28 ","pages":"2040206620950143"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206620950143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39030998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relevance of Ebola virus VP35 homo-dimerization on the type I interferon cascade inhibition","authors":"Francesco Di Palma, G. Daino, V. K. Ramaswamy, A. Corona, A. Frau, E. Fanunza, A. Vargiu, E. Tramontano, P. Ruggerone","doi":"10.1177/2040206619889220","DOIUrl":"https://doi.org/10.1177/2040206619889220","url":null,"abstract":"Ebola virus high lethality relies on its ability to efficiently bypass the host innate antiviral response, which senses the viral dsRNA through the RIG-I receptor and induces type I interferon α/β production. In the bypassing action, the Ebola virus protein VP35 plays a pivotal role at multiple levels of the RIG-I cascade, masking the viral 5′-triphosphorylated dsRNA from RIG-I, and interacting with other cascade components. The VP35 type I interferon inhibition is exerted by the C-terminal domain, while the N-terminal domain, containing a coiled-coil region, is primarily required for oligomerization. However, mutations at key VP35 residues L90/93/107A (VP35-3m) in the coiled-coil region were reported to affect oligomerization and reduce type I interferon antagonism, indicating a possible but unclear role of homo-oligomerization on VP35 interaction with the RIG-I pathway components. In this work, we investigated the VP35 dimerization thermodynamics and its contribution to type I interferon antagonism by computational and biological methods. Focusing on the coiled-coil region, we combined coarse-grained and all-atom simulations on wild type VP35 and VP35-3m homo-dimerization. According to our results, wild type VP35 coiled-coil is able to self-assemble into dimers, while VP35-3m coiled-coil shows poor propensity to even dimerize. Free-energy calculations confirmed the key role of L90, L93 and L107 in stabilizing the coiled-coil homo-dimeric structure. In vitro type I interferon antagonism studies, using full-length wild type VP35 and VP35-3m, revealed that VP35 homo-dimerization is an essential preliminary step for dsRNA binding, which appears to be the main factor of the VP35 RIG-I cascade inhibition, while it is not essential to block the other steps.","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206619889220","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41313940","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 and anti-human immunodeficiency virus activity of substituted ( o,o-difluorophenyl)-linked-pyrimidines as potent non-nucleoside reverse transcriptase inhibitors.","authors":"Lucie Čechová,&nbsp;Milan Dejmek,&nbsp;Ondřej Baszczyňski,&nbsp;David Šaman,&nbsp;Liping Gao,&nbsp;Eric Hu,&nbsp;George Stepan,&nbsp;Petr Jansa,&nbsp;Zlatko Janeba,&nbsp;Petr Šimon","doi":"10.1177/2040206619826265","DOIUrl":"https://doi.org/10.1177/2040206619826265","url":null,"abstract":"<p><p>With the worldwide number of human immunodeficiency virus positive patients stagnant and the increasing emergence of viral strains resistant to current treatment, the development of novel anti-human immunodeficiency virus drug candidates is a perpetual quest of medicinal chemists. Herein, we report a novel group of diarylpyrimidines, non-nucleoside reverse transcriptase inhibitors, which represents an important class of current anti-human immunodeficiency virus therapy. Series of diarylpyrimidines containing o, o-difluorophenyl (A-arm), 4-cyanophenylamino (B-arm), and a small substituent (e.g. NH₂, OMe) at positions 2, 4, and 6 of the pyrimidine ring were prepared. The A-arm was modified in the para position (F or OMe) and linked to the central pyrimidine core with a variable spacer (CO, O, NH). Antiviral activities of 20 compounds were measured against wild type human immunodeficiency virus-1 and mutant reverse transcriptase strains (K103N, Y181C) using a cytoprotection assay. To the most promising structural motives belong the o, o-difluoro- p-methoxy A-arm in position 4, and the amino group in position 6 of pyrimidine. Single digit nanomolar activities with no significant toxicity (CC₅₀ > 17,000 nM) were found for compounds 35 (EC₅₀ = 2 nM), 37 (EC₅₀ = 3 nM), and 13 (EC₅₀ = 4 nM) having O, NH, and CO linkers, respectively.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"27 ","pages":"2040206619826265"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206619826265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36580786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mozobil® (Plerixafor, AMD3100), 10 years after its approval by the US Food and Drug Administration.","authors":"Erik De Clercq","doi":"10.1177/2040206619829382","DOIUrl":"https://doi.org/10.1177/2040206619829382","url":null,"abstract":"<p><p>AMD3100 (plerixafor, Mozobil®) was first identified as an anti-HIV agent specifically active against the T4-lymphotropic HIV strains, as it selectively blocked the CXCR4 receptor. Through interference with the interaction of CXCR4 with its natural ligand, SDF-1 (also named CXCL12), it also mobilized the CD34⁺stem cells from the bone marrow into the peripheral blood stream. In December 2008, AMD3100 was formally approved by the US FDA for autologous transplantation in patients with Non-Hodgkin's Lymphoma or multiple myeloma. It may be beneficially used in various other malignant diseases as well as hereditary immunological disorders such as WHIM syndrome, and physiopathological processes such as hepatopulmonary syndrome.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"27 ","pages":"2040206619829382"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206619829382","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36977503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A medium-throughput screen for inhibitors of human metapneumovirus.","authors":"Jennifer C Becker,&nbsp;Sharon J Tollefson,&nbsp;David Weaver,&nbsp;John V Williams","doi":"10.1177/2040206619830197","DOIUrl":"https://doi.org/10.1177/2040206619830197","url":null,"abstract":"<p><p>Human metapneumovirus, a paramyxovirus discovered in 2001, is a major cause of lower respiratory infection in adults and children worldwide. There are no licensed vaccines or drugs for human metapneumovirus. We developed a fluorescent, cell-based medium-throughput screening assay for human metapneumovirus that captures inhibitors of all stages of the viral lifecycle except budding of progeny virus particles from the cell membrane. We optimized and validated the assay and performed a successful medium-throughput screening. A number of hits were identified, several of which were confirmed to inhibit viral replication in secondary assays. This assay offers potential to discover new antivirals for human metapneumovirus and related respiratory viruses. Compounds discovered using the medium-throughput screening may also provide useful probes of viral biology.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"27 ","pages":"2040206619830197"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206619830197","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36949837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of CXCR4 tropism and CCR5-tropic resistance in treatment-experienced participants receiving maraviroc in the 48-week MOTIVATE 1 and 2 trials.","authors":"Becky Jubb,&nbsp;Marilyn Lewis,&nbsp;Lynn McFadyen,&nbsp;Paul Simpson,&nbsp;Julie Mori,&nbsp;Phylinda Chan,&nbsp;Barry Weatherley,&nbsp;Elna van der Ryst,&nbsp;Mike Westby,&nbsp;Charles Craig","doi":"10.1177/2040206619895706","DOIUrl":"https://doi.org/10.1177/2040206619895706","url":null,"abstract":"Maraviroc blocks HIV-1 entry into CD4+ cells by interrupting the interaction between viral gp120 and cell-surface CCR5. Resistance to CCR5 antagonist–mediated inhibition can develop by unmasking pre-existing CXCR4-using virus or through selection of CCR5-tropic resistant virus, characterized by plateaus in maximum percent inhibition <95%. Here, we examine viral escape in maraviroc-treated participants during virologic failure through Week 48 in the MOTIVATE 1 and 2 trials. Resistance was assessed relative to number of active drugs in participants’ optimized background therapy, pharmacokinetic adherence markers, Baseline demographic data, HIV-1 RNA and CD4+ counts. For participants with R5 virus confirmed (post hoc) at Screening, Baseline genotypic weighted optimized background therapy susceptibility scores (gwOBTSS) were assigned where possible. Through Week 48, 219/392 (56%) participants with an assigned gwOBTSS achieved a virologic response. Of those remaining, 48/392 (12%) had CXCR4-using virus; 58/392 (15%) had R5 virus (maraviroc sensitive: n = 35/392, 9%; maraviroc resistant: n = 18/392, 5%; undeterminable: n = 5/392, 1%) and 67/392 (17%) had no failure tropism result. When optimized background therapy provided limited support to maraviroc (gwOBTSS <2), 143/286 (50%) responded to therapy, while 76/106 (72%) participants with gwOBTSS ≥2 responded (p < 0.001). Resistance rates were highest for participants with gwOBTSS <2, accounting for 45/48 (94%) of total CXCR4-using emergence and 18/18 (100%) of total CCR5-tropic resistance. R5 viruses from participants with gwOBTSS ≥2 (n = 10) were exclusively maraviroc sensitive; five of these participants had pharmacokinetic and/or pill-count markers of non-adherence. When co-administered with a fully active background regimen, maraviroc did not readily generate resistance in the clinical setting. Trial registry name: ClinicalTrials.gov (https://clinicaltrials.gov/), NCT00098722 and NCT00098306","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"27 ","pages":"2040206619895706"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206619895706","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37473908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indolylarylsulfones, a fascinating story of highly potent human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors.","authors":"Valeria Famiglini,&nbsp;Romano Silvestri","doi":"10.1177/2040206617753443","DOIUrl":"https://doi.org/10.1177/2040206617753443","url":null,"abstract":"<p><p>Indolylarylsulfones are a potent class of human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors. In this review, the structure activity relationship (SAR) studies to improve the profile of sulfone L-737,126 discovered by Merck AG have been analysed with focus on introduction of the 3',5'-dimethyl groups at the 3-phenylsulfonyl moiety, the 2-hydroxyethyl tail at the indole-2-carboxamide nitrogen, coupling of the carboxamide nitrogen with one or two glycinamide and alaninamide units, a fluorine atom at position 4 of the indole ring and correlation between configuration of the asymmetric centre and linker length. IAS derivatives look like promising drug candidates for the treatment of AIDS and related infections in combination with other antiretroviral agents.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"26 ","pages":"2040206617753443"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206617753443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35809824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effectiveness of antiviral agents with broad-spectrum activity against chikungunya virus varies between host cell lines.","authors":"Evelyn J Franco,&nbsp;Jaime L Rodriquez,&nbsp;Justin J Pomeroy,&nbsp;Kaley C Hanrahan,&nbsp;Ashley N Brown","doi":"10.1177/2040206618807580","DOIUrl":"https://doi.org/10.1177/2040206618807580","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) is a mosquito-borne virus that has recently emerged in the Western Hemisphere. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. This study aims to evaluate the antiviral activity of commercially available broad-spectrum antivirals against CHIKV. Due to host cell-specific variability in uptake and intracellular processing of drug, we evaluated the antiviral effects of each agent in three cell lines. Antiviral activities of ribavirin (RBV), interferon-alfa (IFN-α) and favipiravir (FAV) were assessed in CHIKV-infected Vero, HUH-7, and A549 cells. CHIKV-infected cells were treated with increasing concentrations of each agent for three days and viral burden was quantified by plaque assay on Vero cells. Cytotoxic effects of RBV, FAV and IFN-α were also evaluated. Antiviral activity differed depending on the cell line used for evaluation. RBV had the greatest antiviral effect in HUH-7 cells (EC₅₀ = 2.575 µg/mL); IFN-α was most effective in A549 cells (EC₅₀ = 4.235 IU/mL); and FAV in HUH-7 cells (EC₅₀ = 20.00 μg/mL). The results of our study show FAV and IFN-α are the most promising candidates, as their use led to substantial reductions in viral burden at clinically achievable concentrations in two human-derived cell lines. FAV is an especially attractive candidate for further investigation due to its oral bioavailability. These findings also highlight the importance of cell line selection for preclinical drug trials.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"26 ","pages":"2040206618807580"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206618807580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36601808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclophilin A as a target in the treatment of cytomegalovirus infections.","authors":"Ashwaq A Abdullah, Rasedee Abdullah, Zeenathul A Nazariah, Krishnan N Balakrishnan, Faez Firdaus J Abdullah, Jamilu A Bala, Mohd-Azmi Mohd-Lila","doi":"10.1177/2040206618811413","DOIUrl":"10.1177/2040206618811413","url":null,"abstract":"<p><strong>Background: </strong>Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity.</p><p><strong>Methods: </strong>Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins.</p><p><strong>Results: </strong>Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug.</p><p><strong>Conclusion: </strong>Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"26 ","pages":"2040206618811413"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bd/e9/10.1177_2040206618811413.PMC6243413.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36692608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa.","authors":"Kerri J Penrose,&nbsp;Chanson J Brumme,&nbsp;Maritsa Scoulos-Hanson,&nbsp;Kristen Hamanishi,&nbsp;Kelley Gordon,&nbsp;Raquel V Viana,&nbsp;Carole L Wallis,&nbsp;P Richard Harrigan,&nbsp;John W Mellors,&nbsp;Urvi M Parikh","doi":"10.1177/2040206618762985","DOIUrl":"https://doi.org/10.1177/2040206618762985","url":null,"abstract":"<p><p>Background Rilpivirine (TMC278LA) is a promising drug for pre-exposure prophylaxis of HIV-1 because of its sub-nanomolar potency and long-acting formulation; however, increasing transmission of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 with potential cross-resistance to rilpivirine could reduce its preventive efficacy. This study investigated rilpivirine cross-resistance among recombinant subtype C HIV-1 derived from 100 individuals failing on first-line non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy in South Africa whose samples were sent for routine HIV-1 drug resistance testing to Lancet Laboratories (Johannesburg, South Africa). Methods Plasma samples were selected from individuals with HIV-1 RNA > 10,000 copies/ml and ≥1 non-nucleoside reverse transcriptase inhibitor-resistance mutation in reverse transcriptase. Recombinant HIV-1_LAI-containing bulk-cloned full-length reverse transcriptase sequences from plasma were assayed for susceptibility to nevirapine (NVP), efavirenz (EFV) and rilpivirine in TZM-bl cells. Fold-change (FC) decreases in drug susceptibility were calculated against a mean IC₅₀ from 12 subtype C HIV-1 samples from treatment-naïve individuals in South Africa. Cross-resistance was evaluated based on biological cutoffs established for rilpivirine (2.5-FC) and the effect of mutation combinations on rilpivirine phenotype. Results Of the 100 samples from individuals on failing antiretroviral therapy, 69 had 2.5- to 75-fold decreased susceptibility to rilpivirine and 11 had >75-fold resistance. Rilpivirine resistance was strongly associated with K103N especially in combination with other rilpivirine-associated mutations. Conclusion The frequently observed cross-resistance of HIV-1 suggests that the preventive efficacy of TMC278LA pre-exposure prophylaxis could be compromised by transmission of HIV-1 from individuals with failure of first-line non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"26 ","pages":"2040206618762985"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206618762985","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35936481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}