Abstract The 3VHE protein is considered as a potential target for the treatment of prostate cancer. In order to find new 3VHE inhibitors, pharmacophore mod els based on the molecular structure of rhodanine derivatives and a three dimensional quantitative structure-activity relationship model (3D-QSAR) have been developed and validated by different methods. The 3D-QSAR model was evaluated for its predictive performance on a diverse test set containing 18 prostate cancer inhibitors. It presents very interesting internal and external statistical validation parameters (SD = 0.081; R2 = 0.903; Q2 = 0.869;2pred r = 0.861 ; F = 247.2). This result suggests that the 3D-QSAR combinatori al model can be used to search for new 3VHE inhibitors and predict their po tential activity. Based on the combinatorial pharmacophore model, a virtual screening of the Enamine database was performed. Compounds selected after virtual screening were subjected to molecular docking protocols (HTVS, SP, XP and IFD). Twenty new active compounds have been identified and their absorption, distribution, metabolism and excretion (ADME) property calcu lated using Schrödinger’s Qikprop module. These results suggest that these new compounds could constitute new chemical starting points for further structural optimization of 3VHE inhibitors.

Abstract Malaria is a real public health problem. It’s one of the pathologies that mobil ize the scientific community. Resistance to existing treatments is the basis for the search for new treatments. Some molecules such as Manzamenones have shown important antimalarial properties. These molecules belong to the fam ily of atypical fatty acid derivatives. This work presents the relative stabilities, some reactivity properties and the privileged sites of interaction by hydrogen bond of fourteen Manzamenones and two antimalarial drugs: quinine and Ar temisinin. These analyses were performed using quantum chemical calculations. We employed the two-layer ONIOM calculation method; namely ONIOM (B3LYP/6-311++G (d, p): AM1) for the fourteen Manzamenones. The geo metries of the two antimalarials are calculated at B3LYP/6-311++G (d, p). The electrostatic potential (ESP) calculation of all molecules is done at the B3LYP/6-31++G (d, p) level. The formation processes of the molecules are discussed from the thermodynamic quantities we have calculated. The rela tive stabilities, the energies of the frontier orbitals, the energy gaps, the dipole moment, etc., are evaluated and discussed. The electrostatic potential at the molecular surface has been used to identify the sites favorable to the forma tion of hydrogen bond.

Abstract The 3VHE protein is considered as a potential target for the treatment of prostate cancer. In order to find new 3VHE inhibitors, pharmacophore models based on the molecular structure of rhodanine derivatives and a three dimensional quantitative structure-activity relationship model (3D-QSAR) have been developed and validated by different methods. The 3D-QSAR model was evaluated for its predictive performance on a diverse test set containing 18 prostate cancer inhibitors. It presents very interesting internal and external statistical validation parameters (SD = 0.081; R2 = 0.903; Q2 = 0.869;2pred r = 0.861 ; F = 247.2). This result suggests that the 3D-QSAR combinatorial model can be used to search for new 3VHE inhibitors and predict their potential activity. Based on the combinatorial pharmacophore model, a virtual screening of the Enamine database was performed. Compounds selected after virtual screening were subjected to molecular docking protocols (HTVS, SP, XP and IFD). Twenty new active compounds have been identified and their absorption, distribution, metabolism and excretion (ADME) property calculated using Schrödinger’s Qikprop module. These results suggest that these new compounds could constitute new chemical starting points for further structural optimization of 3VHE inhibitors.

Abstract Catechin and epicatechin are two isomeric flavonoids. Despite the vital properties highlighted by numerous scientific studies, very little data is available on the intrinsic reactivity of these compounds. To provide more details on the stability and reactivity of catechin and epicatechin, this study is performed by means of theoretical calculation methods. For this purpose, geometry optimizations and frequency calculations at the B3LYP/6-31 + G (d, p) level of theory has been carried out and Natural Bond Orbital (NBO) analysis and VEDA (Vibrational Energy Distribution Analysis). The geometric and energy parameters and NBO analysis show that catechin appears more stable than epicatechin. The hydroxyl group position on the ring C of the catechol structure represents a factor that influences this relative stability. The global and local reactivity parameters reveal that epicatechin becomes more reactive than catechin. They indicate that their hydroxyl groups correspond to their most receptive sites. Fukui indices, VEDA and acidity study establish that O28–H29 remains the most reactive.

Abstract This work was carried out on a series of twenty-two (22) benzimidazole derivatives with inhibitory activities against Mycobacterium tuberculosis H37Rv by applying the Quantitative Structure-Activity Relationship (QSAR) method. The molecules were optimized at the level DFT/B3LYP/6−31 + G (d, p), to obtain the molecular descriptors. We used three statistical learning tools namely, the linear multiple regression (LMR) method, the nonlinear regression (NLMR) and the artificial neural network (ANN) method. These methods allowed us to obtain three (3) quantitative models from the quantum descriptors that are, chemical potential (μ), polarizability (α), bond length l (C = N), and lipophilicity. These models showed good statistical performance. Among these, the ANN has a significantly better predictive ability R2 = 0.9995; RMSE = 0.0149; F = 31879.0548. The external validation tests verify all the criteria of Tropsha et al. and Roy et al. Also, the internal validation tests show that the model has a very satisfactory internal predictive character and can be considered as robust. Moreover, the applicability range of this model determined from the levers shows that a prediction of the pMIC of the new benzimidazole derivatives is acceptable when its lever value is lower than 1.

Abstract The paddy rice degradation remains a concern for research; the chemical phenomena underlying this process persists unknown. This research aims to identify the mechanism of starch degradation. It determines the nature of the reactions between two, three and four synthons of amylose with oryzenin using theoretical methods. The ONIOM (DFT/B3LYP/6 - 31 + G(d, p): AM1) level of theory is performed on four monomers and eight complexes. Frequencies make it possible to obtain energy and spectroscopic quantities. Calculations after geometry optimization. Following this, a “single point” allows exploiting the “Natural Bond Orbital (NBO)” analysis. The first three parameters suggest that the main interactions between oryzenin and amylose arise through O29-H30…O46 hydrogen bonds (HB). Furthermore, this result posits that the length of the amylose doesn’t influence this reaction. The NBO analysis shows that this component of starch degrades first at the end of the chain to produce monosaccharides; it can also alter in the middle of the chain to give disaccharides.