GHTM

Global Health and Tropical Medicine

  • GHTM
    • Vision
    • Mission
    • Governance
    • Scientific Advisory Board
  • News
    • Outreach
    • Events
      • GHTM Sessions
      • Workshops
    • Articles
    • Jobs
  • Research
    • Cross-cutting issues
      • Global Pathogen Dispersion and Population Mobility
      • Drug Discovery and Drug Resistance
      • Diagnostics
      • Public Health Information
      • Fair Research Partnerships
    • Research Groups
      • PPS – Population health, policies and services
      • THOP – TB, HIV and opportunistic diseases and pathogens
      • VBD – Vector borne diseases and pathogens
      • IHC – Individual health care
    • Research in numbers
      • 2020
      • 2019
      • 2018
      • 2017
    • Projects
      • Ongoing Projects
    • Members
      • Population health, policies and services
        • PPS PhD members
        • PPS non PhD members
      • TB, HIV and opportunistic diseases and pathogens
        • THOP PhD members
        • THOP non PhD members
      • Vector-borne diseases and pathogens
        • VBD PhD members
        • VBD non PhD members
      • Individual Health Care
        • IHC PhD members
        • IHC non PhD members
      • Technical / administrative support
  • Publications
  • Education
    • Master Theses
    • PhD Theses
  • Services
Home / Publicações / Bis-alkylamineIndolo[3,2-b]quinolines as hemozoin ligands: implications for antimalarialcytostatic and cytocidal activities

Bis-alkylamineIndolo[3,2-b]quinolines as hemozoin ligands: implications for antimalarialcytostatic and cytocidal activities

  • Autores: Charneira C, Figueiras M, Gut J, Lavrado J, Lopes D, Machado M, Moreira R, Nogueira F, Paulo A, Rosenthal PJ, Santos SA
  • Ano de Publicação: 2014
  • Journal: Journal of Medicinal Chemistry
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/24673163

To get insight into the relevance of targeting hemozoin (Hz) crystals, two isomeric series, N5,N10-bis-alkylamine (2a-k) and N10,O11-bis-alkylamine (3a-k) indolo[3,2-b]quinolines, were evaluated for their in vitro activity against chloroquine (CQ)-resistant and sensitive strains of Plasmodium falciparum.

In general, compounds of series 3 were more active than isomers 2, with IC50/LD50 ranging from 25/233 nM (3i) to 1.3 (3a)/10.7 (3b) μM. SAR analyses showed that lipophilicity and chlorine substitution at C3 increased both cytostatic and cytocidal activities. Both series bound to hematin monomer, inhibited β-hematin formation in vitro, delayed intraerythrocytic parasite development with apparent inhibition of Hz biocrystallization, and showed higher cytocidal activity against schizonts.

In addition, cytostatic and cytocidal activities of series 3, but not those of isomers 2, correlated with calculated vacuole accumulation ratios, suggesting different capacities of 2 and 3 to bind to the Hz crystal face {001} exposed on the vacuole aqueous medium and different mechanisms of cytocidal potency.

Share this:

  • Click to share on Facebook (Opens in new window)
  • Click to share on Twitter (Opens in new window)
  • Click to share on LinkedIn (Opens in new window)
  • Click to share on Pinterest (Opens in new window)
  • Click to share on WhatsApp (Opens in new window)
  • Click to print (Opens in new window)

Events

Fiocruz visits the BIOTROP and Historical Collections

  Fiocruz visits the BIOTROP and Historical Collections of the IHMT-NOVA. On April 17 and … [Read More...]

BIOTROP launches a Lusophone Network of Biobanks

BIOTROP launches a Lusophone Network of Biobanks. On April 19, the GHTM IHMT-NOVA biobank … [Read More...]

IHMT-NOVA held the 3rd WANETAM Steering Committee Meeting

    Between 4th and 5th may, GHTM-IHMT-NOVA held the 3rd WANETAM Steering … [Read More...]

GHTM – 4th Scientific Advisory Board meeting

On April 22nd and 24th 2022, GHTM-IHMT-NOVA held the 4th meeting with the members of GHTM Scientific … [Read More...]

Call for PhD Studentships

The Institute of Hygiene and Tropical Medicine (IHMT), Universidade Nova de Lisboa (NOVA), through … [Read More...]

IHMT | GHTM – APPLICATIONS ARE OPEN!

IHMT | GHTM - Applications are open for three research vacancies:   One position - PhD … [Read More...]

About GHTM

GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

Contacts

Rua da Junqueira, 100
1349-008 Lisboa
Portugal
+351 213 652 600
+351 213 632 105

  • Facebook
  • YouTube

Subscribe Newsletter

  • How to get to GHTM/IHMT
  • GHTM Sessions
  • Research Groups
  • Cross-cutting issues
© Copyright 2023 IHMT-UNL Todos os Direitos Reservados.
  • Universidade Nova de Lisboa
  • Fundação para a Ciência e a Tecnologia

    Project UID/Multi/04413/2013