N-Aryl-2-aminobenzimidazoles: Novel, Efficacious, Antimalarial Lead Compounds
Author(s)
Ramachandran, Sreekanth
Hameed, Shahul P
Srivastava, Abhishek
Shanbhag, Gajanan
Morayya, Sapna
Rautela, Nikhil
Awasthy, Disha
Kavanagh, Stefan
Bharath, Sowmya
Reddy, Jitendar
Panduga, Vijender
Prabhakar, KR
Saralaya, Ramanatha
Nanduri, Robert
Raichurkar, Anandkumar
Menasinakai, Sreenivasaiah
Achar, Vijayashree
Belen Jimenez-Diaz, Maria
Santos Martinez, Maria
Angulo-Barturen, Inigo
Ferrer, Santiago
Maria Sanz, Laura
Javier Gamo, Francisco
Duffy, Sandra
Avery, Vicky M
Waterson, David
Lee, Marcus CS
Coburn-Flynn, Olivia
Fidock, David A
Iyer, Pravin S
Narayanan, Shridhar
Hosagrahara, Vinayak
Sambandamurthy, Vasan K
Year published
2014
Metadata
Show full item recordAbstract
From the phenotypic screening of the AstraZeneca corporate compound collection, N-aryl-2-aminobenzimidazoles have emerged as novel hits against the asexual blood stage of Plasmodium falciparum (Pf). Medicinal chemistry optimization of the potency against Pf and ADME properties resulted in the identification of 12 as a lead molecule. Compound 12 was efficacious in the P. berghei (Pb) model of malaria. This compound displayed an excellent pharmacokinetic profile with a long half-life (19 h) in rat blood. This profile led to an extended survival of animals for over 30 days following a dose of 50 mg/kg in the Pb malaria model. ...
View more >From the phenotypic screening of the AstraZeneca corporate compound collection, N-aryl-2-aminobenzimidazoles have emerged as novel hits against the asexual blood stage of Plasmodium falciparum (Pf). Medicinal chemistry optimization of the potency against Pf and ADME properties resulted in the identification of 12 as a lead molecule. Compound 12 was efficacious in the P. berghei (Pb) model of malaria. This compound displayed an excellent pharmacokinetic profile with a long half-life (19 h) in rat blood. This profile led to an extended survival of animals for over 30 days following a dose of 50 mg/kg in the Pb malaria model. Compound 12 retains its potency against a panel of Pf isolates with known mechanisms of resistance. The fast killing observed in the in vitro parasite reduction ratio (PRR) assay coupled with the extended survival highlights the promise of this novel chemical class for the treatment of malaria.
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View more >From the phenotypic screening of the AstraZeneca corporate compound collection, N-aryl-2-aminobenzimidazoles have emerged as novel hits against the asexual blood stage of Plasmodium falciparum (Pf). Medicinal chemistry optimization of the potency against Pf and ADME properties resulted in the identification of 12 as a lead molecule. Compound 12 was efficacious in the P. berghei (Pb) model of malaria. This compound displayed an excellent pharmacokinetic profile with a long half-life (19 h) in rat blood. This profile led to an extended survival of animals for over 30 days following a dose of 50 mg/kg in the Pb malaria model. Compound 12 retains its potency against a panel of Pf isolates with known mechanisms of resistance. The fast killing observed in the in vitro parasite reduction ratio (PRR) assay coupled with the extended survival highlights the promise of this novel chemical class for the treatment of malaria.
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Journal Title
Journal of Medicinal Chemistry
Volume
57
Subject
Chemical Sciences not elsewhere classified
Medicinal and Biomolecular Chemistry
Organic Chemistry
Pharmacology and Pharmaceutical Sciences