Spiroindolones, a Potent Compound Class for the Treatment of Malaria
- M. Rottmann, C. McNamara, T. Diagana
- Biology, MedicineScience
- 3 September 2010
The preclinical profile for an optimized spiroindolone drug candidate, NITD609, shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in a rodent malaria model.
Ten years of dengue drug discovery: progress and prospects.
- S. Lim, Qing-yin Wang, P. Shi
- BiologyAntiviral Research
- 1 November 2013
Discovery of Dengue Virus NS4B Inhibitors
- Qing-yin Wang, Hongping Dong, P. Shi
- Biology, MedicineJournal of Virology
- 27 May 2015
The results validate, for the first time, that NS4B inhibitors could potentially be developed for antiviral therapy for treatment of DENV infection in humans.
Spirotetrahydro β-Carbolines (Spiroindolones): A New Class of Potent and Orally Efficacious Compounds for the Treatment of Malaria
Improvement of the pharmacokinetic profile of the series translated to exceptional oral efficacy in the P. berghei infected malaria mouse model where full cure was achieved in four of five mice with three daily doses of 30 mg/kg.
A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis
- U. Manjunatha, S. Vinayak, T. Diagana
- Biology, MedicineNature
- 31 May 2017
The results suggest that the Cryptosporidium lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) is a target for pyrazolopyridines and that KDU731 warrants further preclinical evaluation as a drug candidate for the treatment of cryptosporidiosis.
Lead optimization of spiropyrazolopyridones: a new and potent class of dengue virus inhibitors.
- B. Zou, W. Chan, Paul W Smith
- Chemistry, BiologyACS Medicinal Chemistry Letters
- 12 March 2015
Cell-based lead optimization of the spiropyrazolopyridones focusing on improving the physicochemical properties is described, and an optimal compound 14a, with balanced in vitro potency and pharmacokinetic profile, achieved about 1.9 log viremia reduction at 3 × 50 mg/kg (bid) or 3 × 100mg/kg oral doses in the dengue in vivo mouse efficacy model.
Total synthesis of the cyclodepsipeptide apratoxin A and its analogues and assessment of their biological activities.
- D. Ma, B. Zou, G. Cai, Xiaoyi Hu, Jun O. Liu
- Chemistry, BiologyChemistry
- 5 October 2006
Biological analysis revealed that both synthetic apratoxin A and its oxazoline analogue inhibited cell proliferation by causing cell cycle arrest in the G1 phase, suggesting that the two methyl groups at C(37) and C(40) and the stereochemistry at C(-37) are essential for the potent cellular activity of the oxazolin analogue of aprat toxin A.
NITD-688, a pan-serotype inhibitor of the dengue virus NS4B protein, shows favorable pharmacokinetics and efficacy in preclinical animal models
NITD-688, a pan-serotype dengue virus inhibitor, is effective in mice and is well tolerated with favorable pharmacokinetic properties in rats and dogs and decreased viremia in mice when treated up to 2 days after DENV infection, suggesting that NITD -688 is a promising candidate for a DENV antiviral drug.
Lerisetron Analogues with Antimalarial Properties: Synthesis, Structure–Activity Relationship Studies, and Biological Assessment
- R. Mueller, V. Reddy, K. Chibale
- Biology, ChemistryACS Omega
- 17 March 2020
A phenotypic whole cell high-throughput screen against the asexual blood and liver stages of the malaria parasite identified a benzimidazole chemical series and several compounds with improved antiplasmodial potency, relative to the lead compound 3, were identified.
Preclinical Evaluation of the Antifolate QN254, 5-Chloro- N′6′-(2,5-Dimethoxy-Benzyl)-Quinazoline-2,4,6-Triamine, as an Antimalarial Drug Candidate
- A. Nzila, M. Rottmann, T. Diagana
- Biology, MedicineAntimicrobial Agents and Chemotherapy
- 29 March 2010
QN254 does not show the adequate therapeutic index to justify its further development as a single agent, and biochemical and structural evidence that QN254 binds and inhibits the function of both the wild-type and the quadruple-mutant (V1S) forms of the DHFR enzyme is provided.
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