For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
6
views
26
references
 Top references
cited by
0
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      487
      similar
       All similar

      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

      88,007 Monthly downloads/views I 4.319 Impact Factor I 6.6 CiteScore I 1.12 Source Normalized Impact per Paper (SNIP) I 0.784 Scimago Journal & Country Rank (SJR)

       

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Antileishmanial and antitrypanosomal activity of symmetrical dibenzyl-substituted α,β-unsaturated carbonyl-based compounds

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background: Human African Trypanosomiasis (HAT) and leishmaniasis are two of the most neglected challenging tropical diseases, caused by the kinetoplastid parasites Trypanosoma and Leishmania species, respectively. For both of these complex disease spectra, treatment options are limited and threatened by drug resistance, justifying urgent new drug discovery efforts.

          Purpose: In the present study we investigated the antitrypanosomal and antileishmanial activity of a series of 21 symmetrical α,β-unsaturated carbonyl-based compounds, each featuring two 3-methoxybenzene attached to a central cyclohexanone, tetrahydro-4-pyranone scaffold or 4-piperidone ring. Structure-activity relationships were explored with respect to substitution on positions 3, 4 and 6 of the terminal 3-methoxybenzyl groups, and seven types of central ring.

          Results: Compounds 3a, 3o, 3s and 3t, showed broad anti-kinetoplastid activity against all species and strains tested.

          Conclusion: Compound 3o featuring N-methyl-4-piperidone was found to be the most potent analog and therefore can serve as a potential lead for the development of new drug candidates for trypanosomiasis and leishmaniasis.

          Most cited references26

          • Record: found
          • Abstract: found
          • Article: not found

          Continuous cultivation of Trypanosoma brucei blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers.

          H Hirumi, K Hirumi (1989)
          Blood stream forms (BSF) of Trypanosoma brucei brucei GUT at 3.1 were propagated in vitro in the absence of feeder layer cells at 37 C, using a modified Iscove's medium (HMI-18). The medium was supplemented with 0.05 mM bathocuproine sulfonate, 1.5 mM L-cysteine, 1 mM hypoxanthine, 0.2 mM 2-mercaptoethanol, 1 mM sodium pyruvate. 0.16 mM thymidine, and 20% (v/v) Serum Plus (SP) (Hazleton Biologics, Lenexa, Kansas). The latter contained a low level of serum proteins (13 micrograms/ml). Each primary culture was initiated by placing 3.5-4 x 10(6) BSFs isolated from infected mice in a flask containing 5 ml of the medium (HMI-9) supplemented with 10% fetal bovine serum (FBS) and 10% SP. The cultures were maintained by replacing the medium every 24 hr for 5-7 days. During this period, many BSFs died. However, from day 4 onward, long slender BSFs increased in number. On days 5-7, trypanosome suspensions were pooled and cell debris was removed by means of diethylaminoethyl cellulose (DE52) column chromatography. Blood stream forms then were collected by centrifugation, resuspended in fresh medium at 7-9 x 10(5)/ml, and transferred to new flasks. Subcultures were maintained by readjusting the BSF density to 7-9 x 10(5)/ml every 24 hr. Concentrations of FBS were reduced gradually at 5-7-day intervals by alternating the amounts of FBS and SP in HMI-9 with 5% FBS and 15% SP, with 2% FBS and 18% SP, and finally with 20% SP (HMI-18). By this method, 2-3 x 10(6) VSFs/ml were obtained consistently every 24 hr. for more than 80 days.(ABSTRACT TRUNCATED AT 250 WORDS)
          Article 0 comments Cited 303 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro.

            B Räz, M Iten, Y Grether-Bühler … (1997)
            Alamar Blue, an indicator for metabolic cell function, was evaluated as a fluorescent and as a colorimetric dye in drug sensitivity assays for human pathogenic African trypanosomes, Trypanosoma brucei rhodesiense and T.b. gambiense. The experimental conditions were adjusted to find those where the relationship between trypanosome number and Alamar Blue signal was linear over the widest possible range. Fluorescent signals correlated to trypanosome numbers from 10(4) trypanosomes/ml (T.b. rhodesiense) and 10(5) trypanosomes/ml (T.b. gambiense) up to 2-3 x 10(6) trypanosomes/ml when trypanosomes were incubated for 2 h with 10% Alamar Blue. Trypanocidal activity of common drugs (melarsoprol, DFMO, suramin, pentamidine and diminazene aceturate) was determined employing this assay. The IC50 values obtained were comparable to those obtained with another fluorochrome, BCECF-AM. The Alamar Blue assay can be applied for drug screening, since it is simple, reproducible and economical. The assay can also be used in field sites with less equipped laboratories, because in addition to fluorometric endpoint determination, a colorimetric reading is possible.
            Article 0 comments Cited 176 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Epidemiology of visceral leishmaniasis

              Paul Ready (2014)
              Leishmania species are the causative agents of leishmaniasis, a neglected tropical disease. These parasitic protozoans are usually transmitted between vertebrate hosts by the bite of blood sucking female phlebotomine sand flies. This review focuses on the two parasites causing most human visceral leishmaniasis (VL), which leads to substantial health problems or death for up to 400,000 people per year. Except for travel cases, Leishmania donovani infections are restricted to the (sub-)tropics of Asia and Africa, where transmission is mostly anthroponotic, while Leishmania infantum occurs in the drier parts of Latin America as well as in the Mediterranean climate regions of the Old World, with the domestic dog serving as the main reservoir host. The prevalence of VL caused by L. infantum has been declining where living standards have improved. In contrast, infections of L. donovani continue to cause VL epidemics in rural areas on the Indian subcontinent and in East Africa. The current review compares and contrasts these continental differences and suggests priorities for basic and applied research that might improve VL control. Transmission cycles, pathogenesis, diagnosis, treatment and prognosis, prevention (including vector control), surveillance, transmission modeling, and international control efforts are all reviewed. Most case detection is passive, and so routine surveillance does not usually permit accurate assessments of any changes in the incidence of VL. Also, it is not usually possible to estimate the human inoculation rate of parasites by the sand fly vectors because of the limitations of survey methods. Consequently, transmission modeling rarely passes beyond the proof of principle stage, and yet it is required to help develop risk factor analysis for control programs. Anthroponotic VL should be susceptible to elimination by rapid case detection and treatment combined with local vector control, and one of the most important interventions may well be socioeconomic development.
              Article 0 comments Cited 149 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): DDDT
                Journal ID (pmc): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 24 April 2019
                Publication date Collection: 2019
                Volume: 13
                Pages: 1179-1185
                Affiliations
                [1 ]Biology Department, College of Science, Jouf University , Sakaka, Aljouf 2014, Saudi Arabia
                [2 ]Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow , Glasgow G12 8TA, UK
                [3 ]Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University , Sakaka, Aljouf 2014, Saudi Arabia
                Author notes
                Correspondence: Syed Nasir Abbas BukhariDepartment of Pharmaceutical Chemistry, College of Pharmacy, Jouf University , Sakaka, Aljouf2014, Saudi ArabiaTel +96 656 573 8896Email sbukhari@ 123456ju.edu.sa
                Author information
                http://orcid.org/0000-0002-9963-1827
                http://orcid.org/0000-0001-8125-7972
                Article
                Publisher ID: 204733
                DOI: 10.2147/DDDT.S204733
                PMC ID: 6500899
                SO-VID: 9307ff30-fcfa-43fb-991b-7f4690d12634
                Copyright © © 2019 Alkhaldi et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 10 February 2019
                Date accepted : 04 March 2019
                Page count
                Figures: 1, Tables: 2, References: 29, Pages: 7
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: protozoan parasites,sleeping sickness,-α,β-unsaturated carbonyl-based compounds,cyclohexanone,piperidine
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: protozoan parasites, sleeping sickness, -α,β-unsaturated carbonyl-based compounds, cyclohexanone, piperidine

                Comments

                Comment on this article