Using topological indices to predict anti-Alzheimer and anti-parasitic GSK-3 inhibitors by multi-target QSAR in silico screening

• Published in: Molecules (Basel, Switzerland) Vol. 15; no. 8; pp. 5408 - 5422
• Main Authors: García, Isela, Fall, Yagamare, Gómez, Generosa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09-08-2010; MDPI
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - enzymology; Alzheimer's disease; Antiparasitic Agents - chemistry; Antiparasitic Agents - pharmacology; Computational Biology - methods; Discriminant Analysis; Drug Evaluation, Preclinical - methods; Glycogen Synthase Kinase 3 - antagonists & inhibitors; Glycogen Synthase Kinase 3 - metabolism; glycogen synthase kinase-3 (GSK-3) inhibitors; Humans; Kinases; Leishmania; Parasites; Parasitic diseases; Plasmodium falciparum; Protein Kinase Inhibitors - antagonists & inhibitors; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protozoa; QSAR; Quantitative Structure-Activity Relationship; Reproducibility of Results; Software; Trypanosoma brucei
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules15085408

Plasmodium falciparum, Leishmania, Trypanosomes, are the causers of diseases such as malaria, leishmaniasis and African trypanosomiasis that nowadays are the most serious parasitic health problems worldwide. The great number of deaths and the few drugs available against these parasites, make necessary the search for new drugs. Some of these antiparasitic drugs also are GSK-3 inhibitors. GSKI-3 are candidates to develop drugs for the treatment of Alzheimer's disease. In this work topological descriptors for a large series of 3,370 active/non-active compounds were initially calculated with the ModesLab software. Linear Discriminant Analysis was used to fit the classification function and it predicts heterogeneous series of compounds like paullones, indirubins, meridians, etc. This study thus provided a general evaluation of these types of molecules.