An Invitation to Open Innovation in Malaria Drug Discovery: 47 Quality Starting Points from the TCAMS

Calderón, Félix; Barros, David; Bueno, José María; Coteron, Jose M.; Fernández, Esther; Gamo, Francisco Javier; Lavandera, José Luís; León, María Luisa; Macdonald, Simon J. F.; Mallo, A.; Manzano, Pilar; Porras, Esther; Fiandor, José M.; Castro, Julia

doi:10.1021/ml200135p

Cited by 73 publications

(77 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The RO5 can be a useful reference to predict the quality of a structure to be an orally available drug-like compound [13,16], which was outlined by Calderon et al for TCMDC-137332 [8]. Considering the molecular weight (<380 g/mol), the amount of H-bond acceptors (ď6) and H-bond donors (ď3), the values of every compound in this series comply with the proposed values of Lipinski et al [13].…”

Section: Calculations Of Rule-of-five-propertiessupporting

confidence: 57%

“…all derivatives. The RO5 can be a useful reference to predict the quality of a structure to be an orally available drug-like compound [13,16], which was outlined by Calderon et al for TCMDC-137332 [8].…”

Section: Calculations Of Rule-of-five-propertiesmentioning

confidence: 99%

“…The assumed high antiplasmodial activity of TCMDC-137332 (1) could not be confirmed by these assays. available drug-like compound [13,16], which was outlined by Calderon et al for TCMDC-137332 [8].…”

Section: In Vitro Assaymentioning

confidence: 99%

“…13,533 of these, known as the Tres Cantos Antimalarial Compound Set (TCAMS), were active against the malaria parasite Plasmodium falciparum and inhibited the parasite growth by at least 80% at 2 µM concentration. In silico clustering and filtering of the TCAMS set performed by Calderon et al resulted in 552 compounds which were declared as "quality starting points from the TCAMS" [8]. Since then, a few of the compound classes have been further examined, e.g., cyclopropylcarboxamides [9], 2-amino-1-phenylethanols [10], aminohydantoines [11] or carbamoyltriazoles [12].…”

Section: Introductionmentioning

confidence: 99%

“…One of the 552 promising compounds is TCMDC-137332 (1), which has an estimated IC50 value of 7 nM and therefore seemed to be one of the most potent structures of this collection [7,8]. We decided to further investigate this compound which matches nearly all criteria of the Lipinski rules for orally available drugs [13] (Figure 1) and is structurally dissimilar to currently known antimalarials [14].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum

Weidner

Nasereddin²,

Preu

et al. 2016

Molecules

View full text Add to dashboard Cite

Abstract:The Tres Cantos Antimalarial Compound Set (TCAMS) is a publicly available compound library which contains 13533 hit structures with confirmed activity against Plasmodium falciparum, the infective agent responsible for malaria tropica. The TCAMS provides a variety of starting points for the investigation of new antiplasmodial drug leads. One of the promising compounds is TCMDC-137332, which seemed to be a good starting point due to its antiplasmodial potency and its predicted physicochemical properties. Several new analogues based on a 2-phenoxyanilide scaffold were synthesized by standard amide coupling reactions and were fully characterized regarding their identity and purity by spectroscopic and chromatographic methods. Furthermore, the results of the biological evaluation of all congeners against Plasmodium falciparum NF54 strains are presented. The findings of our in vitro screening could not confirm the presumed nanomolar antiplasmodial activity of TCMDC-137332 and its derivatives.

show abstract

Section: Calculations Of Rule-of-five-propertiessupporting

confidence: 57%

Section: Calculations Of Rule-of-five-propertiesmentioning

confidence: 99%

Section: In Vitro Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum

Weidner

Nasereddin²,

Preu

et al. 2016

Molecules

View full text Add to dashboard Cite

show abstract

2010 to 2020: Ten Years of Malaria Drug Discovery

Yeung

Calderón

2021

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

The seventh edition of Burger's Medicinal Chemistry, Drug Discovery and Development included an extensive review of antimalarial drugs and drug targets. Since it was published nearly 10 years ago, the annual number of deaths due to malaria in endemic countries have steadily declined. However, over the past two years, a stabilization in number of malaria deaths hints to a reversal of this trend. This may be in part due to parasite evolution to overcome efficacy of antimalarial therapies, including the now well‐established spread of resistance to artemisinin‐combination therapies in Southeast Asia. Fortunately, the last decade also witnessed a renewed effort by academic researchers, product development partnerships, and pharmaceutical companies to restart malaria drug discovery. Innovations in high‐throughput screening, assay development, access to large chemical libraries, advancements in parasite biology, and whole‐genome sequencing have resulted in the discovery of new antimalarial drugs as well as novel targets. These new drug candidates, which kill the parasite through new mechanisms of action have bolstered the malaria drug development pipeline since the last edition. This article summarizes the new drug discovery approaches and achievements over the past decade.

show abstract

Diversity‐Oriented Synthesis and Drug Development: Facilitating the Discovery of Novel Probes and Therapeutics

Duvall¹,

Comer²,

Dandapani³

2013

Diversity‐Oriented Synthesis

View full text Add to dashboard Cite

An Invitation to Open Innovation in Malaria Drug Discovery: 47 Quality Starting Points from the TCAMS

Abstract: Funding SourcesGlaxoSmithKline acknowledges financial support from Medicines for Malaria Venture (MMV). ' ACKNOWLEDGMENTGlaxoSmithKline acknowledges the perceptive and helpful advice from Jeremy Burrows and Mike Witty.

Cited by 73 publications

References 15 publications

Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum

Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum

2010 to 2020: Ten Years of Malaria Drug Discovery

Diversity‐Oriented Synthesis and Drug Development: Facilitating the Discovery of Novel Probes and Therapeutics

Contact Info

Product

Resources

About