Computational protocol: A New Set of Chemical Starting Points with Plasmodium falciparum Transmission-Blocking Potential for Antimalarial Drug Discovery

Similar protocols

Protocol publication

[…] This chemical analytical method first comprised clustering of the 56 drug-like hits prioritized from the HTS into 39 clusters by using the Complete Linkage algorithm implemented in the Scaffold Hunter program []. These clusters were complemented with all the analogs in TCAMS showing a Tanimoto similarity ≥ 0.8 to any of the 56 prioritized compounds (molecules were represented by topological fingerprints in the RDKit cheminformatic toolkit []). These expanded clusters were characterized in terms of evidence of gametocyte activity in the neighborhood of the prioritized hits by calculating for each of them the hypergeometric probability p(m,n) of having m active compounds (> 50% inhibition at 5 μM) within the n members of the cluster. Larger clusters with an ‘unusually’ high proportion of actives are improbable and, therefore, will have a low value of p. These clusters show the largest opportunity for chemical expansion of the prioritized hits within TCAMS. […]

Pipeline specifications

Software tools Scaffold Hunter, RDKit
Application Drug design
Organisms Plasmodium falciparum
Diseases Malaria, Malaria, Falciparum, Drug-Related Side Effects and Adverse Reactions