Predicting antitrichomonal activity: A computational screening using atom-based bilinear indices and experimental proofs

Existing Trichomonas vaginalis therapies are out of reach for most trichomoniasis people in developing countries and, where available, they are limited by their toxicity (mainly in pregnant women) and their cost. New antitrichomonal agents are needed to combat emerging metronidazole-resistant trichomoniasis and reduce the side effects associated with currently available drugs. Toward this end, atom-based bilinear indices, a new TOMOCOMD-CARDD molecular descriptor, and linear discriminant analysis (LDA) were used to discover novel, potent, and non-toxic lead trichomonacidal chemicals. Two discriminant functions were obtained with the use of non-stochastic and stochastic atom-type bilinear indices for heteroatoms and H-bonding of heteroatoms. These atomic-level molecular descriptors were calculated using a weighting scheme that includes four atomic labels, namely atomic masses, van der Waals volumes, atomic polarizabilities, and atomic electronegativities in Pauling scale. The obtained LDA-based QSAR models, using non-stochastic and stochastic indices, were able to classify correctly 94.51% (90.63%) and 93.41% (93.751/o) of the chemicals in training (test) sets, respectively. They showed large Matthews' correlation coefficients (C