Theoretical modeling and design of some pyrazolopyrimidine derivatives as inhibitors, targeting lymphatic filariasis and onchocerciasis.

Lymphatic filariasis and onchocerciasis are two common filarial diseases caused by a group of parasitic nematodes called filarial worms, which play host to the bacteria organism . One good treatment approach seeks as drug target. Here, a QSAR study was conducted to investigate the anti- activities (pEC) of 52 pyrazolopyrimidine analogues, while using the built model to predict the pEC values of the newly designed analogues. Density Functional Theory was used for the structural optimization, while the model building was based on Genetic Function Algorithm approach. The built QSAR model was validated thus: R = 0.8104, R  = 0.7629, Q  = 0.6981, R  = 0.7501 and cRp = 0.7476. The predicted pEC of all newly designed compounds were higher than that of the template (). The new compounds were; observed to pass the drug-likeness criteria, uniformly distributed to the brain, and found to be non-mutagenic. Also, the new compounds and the reference drug (doxycycline), were docked onto Ovarian Tumor (OTU) deubiquitinase receptor (PDB ID: 6W9O) using iGEMDOCK tool. This protein is known to help subvert host ubiquitin signaling. The resulting binding scores of the newly designed compounds except were higher than that of doxycycline, while the protein-ligand interactions were majorly characterized by Hydrogen-bonding and hydrophobic interaction types. Therefore, the newly designed molecules could be developed as potential drug candidates for the treatment of lymphatic filariasis and onchocerciasis.