Discovery of a novel lead structure for anti-malarials.

  title={Discovery of a novel lead structure for anti-malarials.},
  author={Jochen Wiesner and Pia Wissner and Hans Martin Dahse and Hassan Jomaa and Martin Schlitzer},
  journal={Bioorganic \& medicinal chemistry},
  volume={9 3},
From a library of 61 compounds available from former studies 2,5-bis-acylaminobenzophenone 7p was identified as a lead structure for a novel class of anti-malaria agents active against multi-resistant Plasmodium falciparum strain Dd2. Some structural modifications of this initial lead demonstrated the potential for further improvement of the anti-plasmodial activity of this novel class of anti-malarials. 
Structure-activity relationships of novel anti-malarial agents. Part 7: N-(3-benzoyl-4-tolylacetylaminophenyl)-3-(5-aryl-2-furyl)acrylic acid amides with polar moieties.
It is demonstrated that different moieties with hydrogen bond acceptor properties lead to equipotent or even improved anti-malarial activity in comparison to the nitro group described before. Expand
Structure-activity relationships of novel anti-malarial agents: part 5. N-(4-acylamino-3-benzoylphenyl)-[5-(4-nitrophenyl)-2-furyl]acrylic acid amides.
It is demonstrated that the acyl residue at the 2-amino group of the benzophenone core structure has to be a phenylacetic acid substructure substituted in its para-position with methyl or other substituents of similar size. Expand
Structure-activity relationships of novel anti-malarial agents. Part 4: N-(3-benzoyl-4-tolylacetylaminophenyl)-3-(5-aryl-2-furyl)acrylic acid amides.
This work has invesigated acryloyl derivatives carrying a biaryl structure consisting of a terminal aryl residue and a central 2-furyl ring and deduced that there has to be a lipophilic moiety in the para-position of the terminal phenyl residue. Expand
Structure-activity relationships of novel anti-malarial agents. Part 3: N-(4-acylamino-3-benzoylphenyl)-4-propoxycinnamic acid amides.
Deviations from the phenylacetic acid substructure, shifting the substituent into the ortho-position or bulkier para-substituents resulted in a significant reduction in anti-malarial activity. Expand
3D-QSAR analysis of antimalarial farnesyltransferase inhibitors based on a 2,5-diaminobenzophenone scaffold.
It is found that steric, electrostatic, and hydrophobic properties of substituent groups play key roles in the bioactivity of the series of compounds, while hydrogen bonding interactions show no obvious impact. Expand
Novel antiplasmodial agents
  • M. Go
  • Biology, Medicine
  • Medicinal research reviews
  • 2003
A review of the literature shows that there is a growing trend towards the development of target‐specific antimalarial agents (for example, agents inhibiting plasmodial farnesyl transferase, cyclin dependent kinases, proteases, choline transport), and an increasing number of reports focus on theDevelopment of chemosensitizers, agents that are capable of reversing plas modial resistance. Expand
Recent advances in the search for newer antimalarial agents.
The significant genomic advances resulting in genome sequencing of anopheles gambiae —the major mosquito vector— and plasmodium falciparum —the parasite for deadliest form of malaria— have opened new hopes toward the control of malaria. Expand
Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity
A small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana Trypanosoma Brucei brucei for antitrypanosomal activity, presenting the possibility of these compounds serving as broad-spectrum antibiotics for these prevalent three human pathogens. Expand
Combined docking methods and molecular dynamics to identify effective antiviral 2, 5-diaminobenzophenonederivatives against SARS-CoV-2
The identification of two compounds 35 and 36 having high binding affinity, good pharmacokinetics properties and lowest toxicity are shown that would have the potential to act as promising drug-candidates and would be of interest as starting point for designing compounds against the SARS-CoV-2. Expand
Recent advances in antimalarial drug development
This review provides an in‐depth look at the most significant progress made during the past 10 years in antimalarial drug development. Expand


Design, Synthesis, and Evaluation of Novel Modular Bisubstrate Analogue Inhibitors of Farnesyltransferase.
A novel class of modular bisubstrate farnesyltransferase inhibitors is presented that can be synthesized in a straightforward manner and has an IC50 value of 3.7 μM. Expand
Design, synthesis and early structure-activity relationship of farnesyltransferase inhibitors which mimic both the peptidic and the prenylic substrate.
A class of novel compounds that mimic a bisubstrate inhibitor structure and that differ from the known ones by lacking peptidic or farnesylic substructures are developed. Expand
Non-thiol farnesyltransferase inhibitors: the concept of benzophenone-based bisubstrate analogue farnesyltransferase inhibitors.
Transformation of carboxylic acid derivatives into bisubstrate analogues by addition of a lipophilic alkyl chain, which should be able to occupy considerable portions of the farnesyl binding region in thefarnesyltransferase's active site, resulted in a regain of the inhibitory activity. Expand
Non-peptidic, non-prenylic bisubstrate farnesyltransferase inhibitors. Part 3: structural requirements of the central moiety for farnesyltransferase inhibitory activity.
It is shown that the amide function connecting the farnesyl-mimetic and the linking substructures of the authors' inhibitors is crucial for their activity and is bound to the essential zinc ion in thefarnesyltransferases active center. Expand
Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique.
A rapid, semiautomated microdilution method was developed for measuring the activity of potential antimalarial drugs against cultured intraerythrocytic asexual forms of the human malaria parasite Plasmodium falciparum, and results demonstrated that the method is sensitive and precise. Expand
Human malaria parasites in continuous culture.
Plasmodium falciparum can now be maintained in continuous culture in human erythrocytes incubated at 38 degrees C in RPMI 1640 medium with human serum under an atmosphere with 7 percent carbonExpand
A new year greeting from a new editor
The position of Editor-in-Chief of the authors' Journal has traditionally been filled by a well-established investigator in Hematology, who had convincingly demonstrated both scientific expertise and experience. Expand