Studies of trypanocidal (inhibitory) power of naphthoquinones: evaluation of quantum chemical molecular descriptors for structure–activity relationships

Electronic, lipophilic and steric descriptors included in QSAR-2D and -3D are analyzed for a set of ortho- and para-naphthoquinones that have proved to be powerful oxidative agents with potent trypanocidal activities specially against Leptomonas seymouri and Trypanosoma cruzi. Electronic properties are calculated by means of semiempirical (PM3), ab initio (HF/3-21G) and density functional theory (B3LYP/6-31 + G∗) methodologies. Three different electronic states, neutral quinones, hydroquinones and semiquinones, are studied to investigate if any one of them are statistically related with the biological activities. The best correlations were obtained at the B3LYP level of theory because it includes electronic correlation. The QSAR-2D indicates that the best trypanocidal growth inhibitors are molecules in the semiquinone electronic state, with the following properties: (a) high negative value of EHOMO, (b) high negative charge in the oxygen atoms of the carbonyl groups, (c) high positive charge in the carbon atom of one of carbonyl moieties and (d) high electronegativity (χ). In a complementary way, the QSAR-3D indicates that the electrostatic field correlates with trypanocidal activity and the presence of bulk moieties would increase activity. The idea of comparing the three electronic states may prove to be of most importance in the general strategy to the design of new trypanocidal drugs. In fact, the experimental results showed that semiquinone is the one really statistically relevant indicating a clear connection between biochemical and theoretical aspects. Finally, we demonstrated that to be a good anti-trypanosomatid compound, the molecule must be a good electron acceptor to reach easily the essential semiquinone state. We expect that the present results motivate new experimental as well as theoretical investigations that confirm our findings.Fil: Paulino, M.. Bioinformatics and Molecular Biomodelling Laboratory ; UruguayFil: Alvareda, E. M.. Bioinformatics and Molecular Biomodelling Laboratory ; UruguayFil: Denis, P. A.. Bioinformatics and Molecular Biomodelling Laboratory ; UruguayFil: Barreiro, E. J.. Universidade Federal do Rio de Janeiro; BrasilFil: Sperandio da Silva, G. M.. Universidade Federal do Rio de Janeiro; BrasilFil: Dubin, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Castellú, C.. Laboratorio Horus; UruguayFil: Aguilera, S.. Universidad Católica de Chile; ChileFil: Tapia, O.. Uppsala University. Department of Physical and Analytical Chemistry; Sueci

Modeling the Transport of Human Rotavirus and Norovirus in Standardized and in Natural Soil Matrix-Water Systems

We modeled Group A Rotavirus (RVA) and Norovirus genogroup II (GII NoV) transport experiments in standardized (crystal quartz sand and deionized water with adjusted pH and ionic strength) and natural soil matrix-water systems (MWS). On the one hand, in the standardized MWS, Rotavirus and Norovirus showed very similar breakthrough curves (BTCs), showing a removal rate of 2 and 1.7 log10, respectively. From the numerical modeling of the experiment, transport parameters of the same order of magnitude were obtained for both viruses. On the other hand, in the natural MWS, the two viruses show very different BTCs. The Norovirus transport model showed significant changes; BTC showed a removal rate of 4 log10, while Rotavirus showed a removal rate of 2.6 log10 similar to the 2 log10 observed on the standardized MWS. One possible explanation for this differential behavior is the difference in the isoelectric point value of these two viruses and the increase of the ionic strength on the natural MWS

Evaluation of Bacterial Contamination as an Indicator of Viral Contamination in a Sedimentary Aquifer in Uruguay

In Uruguay, groundwater is frequently used for agricultural activities, as well as for human consumption in urban and rural areas. As in many countries worldwide, drinking water microbiological quality is evaluated only according to bacteriological standards and virological analyses are not mentioned in the legislation. In this work, the incidence of human viral (Rotavirus A, Norovirus GII, and human Adenovirus) and bacterial (total and thermotolerant coliform and Pseudomonas aeruginosa) contamination in groundwater in the Salto district, Uruguay, as well as the possible correlation between these groups of microorganisms, was studied. From a total of 134 groundwater samples, 42 (32.1%) were positive for Rotavirus, only 1 (0.7%) for both Rotavirus and Adenovirus, and 96 (72.6%) samples were positive for bacterial indicators. Results also show that Rotavirus presence was not associated with changes in chemical composition of the aquifer water. Bacteriological indicators were not adequate to predict the presence of viruses in individual groundwater samples (well scale), but a deeper spatial–temporal analysis showed that they are promising candidates to assess the viral contamination degree at aquifer scale, since from the number of wells with bacterial contamination the number of wells with viral contamination could be estimated

Modeling the Transport of Human Rotavirus and Norovirus in Standardized and in Natural Soil Matrix-Water Systems.

We modeled Group A Rotavirus (RVA) and Norovirus genogroup II (GII NoV) transport experiments in standardized (crystal quartz sand and deionized water with adjusted pH and ionic strength) and natural soil matrix-water systems (MWS). On the one hand, in the standardized MWS, Rotavirus and Norovirus showed very similar breakthrough curves (BTCs), showing a removal rate of 2 and 1.7 log10, respectively. From the numerical modeling of the experiment, transport parameters of the same order of magnitude were obtained for both viruses. On the other hand, in the natural MWS, the two viruses show very different BTCs. The Norovirus transport model showed significant changes; BTC showed a removal rate of 4 log10, while Rotavirus showed a removal rate of 2.6 log10 similar to the 2 log10 observed on the standardized MWS. One possible explanation for this differential behavior is the difference in the isoelectric point value of these two viruses and the increase of the ionic strength on the natural MWS

Evaluation of Bacterial Contamination as an Indicator of Viral Contamination in a Sedimentary Aquifer in Uruguay.

In Uruguay, groundwater is frequently used for agricultural activities, as well as for human consumption in urban and rural areas. As in many countries worldwide, drinking water microbiological quality is evaluated only according to bacteriological standards and virological analyses are not mentioned in the legislation. In this work, the incidence of human viral (Rotavirus A, Norovirus GII, and human Adenovirus) and bacterial (total and thermotolerant coliform and Pseudomonas aeruginosa) contamination in groundwater in the Salto district, Uruguay, as well as the possible correlation between these groups of microorganisms, was studied. From a total of 134 groundwater samples, 42 (32.1%) were positive for Rotavirus, only 1 (0.7%) for both Rotavirus and Adenovirus, and 96 (72.6%) samples were positive for bacterial indicators. Results also show that Rotavirus presence was not associated with changes in chemical composition of the aquifer water. Bacteriological indicators were not adequate to predict the presence of viruses in individual groundwater samples (well scale), but a deeper spatial-temporal analysis showed that they are promising candidates to assess the viral contamination degree at aquifer scale, since from the number of wells with bacterial contamination the number of wells with viral contamination could be estimated

Modeling the Transport of Human Rotavirus and Norovirus in Standardized and in Natural Soil Matrix-Water Systems.

We modeled Group A Rotavirus (RVA) and Norovirus genogroup II (GII NoV) transport experiments in standardized (crystal quartz sand and deionized water with adjusted pH and ionic strength) and natural soil matrix-water systems (MWS). On the one hand, in the standardized MWS, Rotavirus and Norovirus showed very similar breakthrough curves (BTCs), showing a removal rate of 2 and 1.7 log10, respectively. From the numerical modeling of the experiment, transport parameters of the same order of magnitude were obtained for both viruses. On the other hand, in the natural MWS, the two viruses show very different BTCs. The Norovirus transport model showed significant changes; BTC showed a removal rate of 4 log10, while Rotavirus showed a removal rate of 2.6 log10 similar to the 2 log10 observed on the standardized MWS. One possible explanation for this differential behavior is the difference in the isoelectric point value of these two viruses and the increase of the ionic strength on the natural MWS