New orally active diphenylmethyl-based ester analogues of dihydroartemisinin: Synthesis and antimalarial assessment against multidrug-resistant Plasmodium yoelii nigeriensis in mice

2016 ◽  
Vol 26 (6) ◽  
pp. 1536-1541 ◽  
Author(s):  
Sandeep Chaudhary ◽  
Niraj K. Naikade ◽  
Mohit K. Tiwari ◽  
Lalit Yadav ◽  
Bharti Rajesh K. Shyamlal ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Plasmodium Yoelii ◽  
Orally Active

6-(4′-Aryloxy-phenyl)vinyl-1,2,4-trioxanes: A new series of orally active peroxides effective against multidrug-resistant Plasmodium yoelii in Swiss mice

2010 ◽  
Vol 20 (15) ◽  
pp. 4459-4463 ◽  
Author(s):  
Chandan Singh ◽  
Ved Prakash Verma ◽  
Niraj Krishna Naikade ◽  
Ajit Shankar Singh ◽  
Mohammad Hassam ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Plasmodium Yoelii ◽  
Swiss Mice ◽  
Orally Active ◽  
Phenyl Vinyl

scholarly journals Sontochin as a Guide to the Development of Drugs against Chloroquine-Resistant Malaria

2012 ◽  
Vol 56 (7) ◽  
pp. 3475-3480 ◽  
Author(s):  
Sovitj Pou ◽  
Rolf W. Winter ◽  
Aaron Nilsen ◽  
Jane Xu Kelly ◽  
Yuexin Li ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Plasmodium Yoelii ◽  
Significant Activity ◽  
Drug Resistant ◽  
Content Type ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Derivatives Of

ABSTRACTSontochin was the original chloroquine replacement drug, arising from research by Hans Andersag 2 years after chloroquine (known as “resochin” at the time) had been shelved due to the mistaken perception that it was too toxic for human use. We were surprised to find that sontochin, i.e., 3-methyl-chloroquine, retains significant activity against chloroquine-resistant strains ofPlasmodium falciparum in vitro. We prepared derivatives of sontochin, “pharmachins,” with alkyl or aryl substituents at the 3 position and with alterations to the 4-position side chain to enhance activity against drug-resistant strains. Modified with an aryl substituent in the 3 position of the 7-chloro-quinoline ring, Pharmachin 203 (PH-203) exhibits low-nanomolar 50% inhibitory concentrations (IC50s) against drug-sensitive and multidrug-resistant strains andin vivoefficacy against patent infections ofPlasmodium yoeliiin mice that is superior to chloroquine. Our findings suggest that novel 3-position aryl pharmachin derivatives have the potential for use in treating drug resistant malaria.

Synthesis of novel 1,2,4-trioxanes and antimalarial evaluation against multidrug-resistant Plasmodium yoelii nigeriensis

2021 ◽  
pp. 128305
Author(s):  
Monika Shukla ◽  
Mohammad Hassam ◽  
Dinesh Kumar Yadav ◽  
Siddharth Sharma ◽  
Chandan Singh ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Plasmodium Yoelii

Plasmodium yoelii nigeriensis (MDR)—Efficacy of Oral Pyronaridine against Multidrug-Resistant Malaria in Swiss Mice

2000 ◽  
Vol 94 (3) ◽  
pp. 190-193 ◽  
Author(s):  
Renu Tripathi ◽  
Aseem Umesh ◽  
Meenu Mishra ◽  
S.K. Puri ◽  
G.P. Dutta
Keyword(s):  
Multidrug Resistant ◽  
Plasmodium Yoelii ◽  
Swiss Mice

scholarly journals Ribonucleotide reductase, a novel target for gonorrhea

2020 ◽  
Author(s):  
J. Narasimhan ◽  
S. Letinski ◽  
S. Jung ◽  
A. Gerasyuto ◽  
J. Wang ◽  
...  
Keyword(s):  
Ribonucleotide Reductase ◽  
Therapeutic Potential ◽  
Multidrug Resistant ◽  
Resistance Mutations ◽  
Antibiotic Resistant ◽  
Α Subunit ◽  
Negative Stain ◽  
Negative Stain Electron Microscopy ◽  
Novel Target ◽  
Orally Active

AbstractAntibiotic resistant Neisseria gonorrhoeae (Ng) are an emerging public health threat due to increasing numbers of multidrug resistant (MDR) organisms. We identified two novel orally active inhibitors, PTC-847 and PTC-672, that exhibit a narrow spectrum of activity against Ng including MDR isolates. By selecting organisms resistant to the novel inhibitors and sequencing their genomes, we identified a new therapeutic target, the class Ia ribonucleotide reductase (RNR). Activity studies and negative stain electron microscopy of the Ng Ia RNR suggest that these inhibitors potentiate conversion of its active α2β2 state to an inactive α4β4 similar to states first identified with the Escherichia coli (Ec) Ia RNR. Resistance mutations in Ng map to the N-terminal, ATP cone domain of its α subunit and disrupt the interaction with the β subunit required to form the specific quaternary inhibited state. Oral administration of PTC-672 reduces Ng infection in a mouse model and may have therapeutic potential for treatment of Ng that is resistant to current drugs.

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