Computer-aided molecular design of 2-anilino 4-amino substituted quinazolines derivatives as malarial inhibitors

Quantitative structure–activity relationship studies conducted on forty-five (45) derivatives of 2-anilino 4-amino substituted quinazolines as malaria inhibitors to determine the structures responsible for their antimalarial properties and design novel derivatives with improved activities. The molecular descriptors generated were selected to develop the theoretical model using the genetic approximation component of the material studio. The developed model found to be a function of ATSC8c, GATS8i, SpMin1_Bhi, JGI10, and TDB6u descriptors, shows excellent statistical parameters (R2 = 0.7913, R2adj = 0.7553, Q2cv = 0.7112, LOF = 0.2125, and R2pred = 0.7650). The mean effect (MF) analysis revealed the descriptor SpMin1_Bhi, as the most influential by its largest percentage contribution (54%) to the developed model. The descriptor decodes the information on the first ionization potentials and was found to have positive MF. Hence, activity increases with increases the descriptor value. Structural modifications of the template (compound 13; pEC50 = 7.387) using electron-withdrawing groups increases the descriptor value (first ionization potentials) of the template, which by extension increases the antimalarial activity lead to the design of ten (10) novel theoretical derivatives with improve antimalarial activities. Compound 3, N4-(3-bromo-5-fluorobenzyl)-N2-(4-fluorophenyl)-6,7-dimethoxyquinazoline-2,4-diamine was found to have the highest antimalarial activities among all the designed derivatives (pEC50 = 8.0515).

New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation

Phosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new N’-(diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (1H and 13C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effect against the human colon carcinoma (HCT-116) cell line. Our cheminformatics analysis indicated that the para-tailored derivatives [p-NO2 (3) and p-CF3 (7)] have better ionization potentials based on calculated Moran autocorrelations and ionization potentials. Subsequent in vitro cell proliferation assays validated our cheminformatics results by providing experimental evidence that both derivatives 3 and 7 exhibited improved antiproliferative activities against HCT-116. Hence, our results emphasized the importance of electron-withdrawing groups and hydrogen bond-acceptors in the rational design of small-molecule chemical ligands targeting PI3Kα. These results agreed with the induced-fit docking against PI3Kα, highlighting the role of p-substituted aromatic rings in guiding the ligand-PI3Kα complex formation, by targeting a hydrophobic pocket in the ligand-binding site and forming π-stacking interactions with a nearby tryptophan residue.

Релятивистские расчеты химических свойств сверхтяжелого элемента с Z=119 и его гомологов

Relativistic calculations of the electronic structure of the superheavy element of the eighth period - eka-francium (Z=119) and its homologues, which form the group of alkali metals, are performed in the framework of the configuration-interaction method and many-body perturbation theory using the basis of the Dirac-Fock-Sturm orbitals (DFS). The obtained values of the ionization potentials, electron affinities, and root-mean-square radii are compared with the corresponding values calculated within the non-relativistic approximation. A comparison with the available experimental data and the results of previous theoretical calculations is given as well. The analysis of the obtained results indicates a significant influence of the relativistic effects for the francium and eka-francium atoms, which leads to a violation of the monotonic behaviour of the listed above chemical properties as a function of the alkaline-element atomic number. In addition, the quantum electrodynamics corrections to the ionization potentials are evaluated by employing the model Lamb-shift operator (QEDMOD).

Theoretical investigation of the single and double ionization spectra of M(CO)6, M=W

In this work, we study the single and double ionization spectra of the M(CO)6,with M =( W and Cr ) complexes by applying the four-component algebraic diagrammatic construction and Fock-space coupled cluster methods to extend earlier studies based on less demanding approaches. The computed single and double ionization potentials are in good agreement comparing with the available experimental results. The electronic structures of the cationic molecular systems are carefully investigated by computing accurately single and double ionization potentials. The final state characterization is relied on group theoretical considerations of the contributing orbitals and allowed for a clear assignment. Energy level diagrams show the effect of spin-orbit (SO) coupling starting from scalar relativistic results and for the heavy representative M(CO)6 with M =( W and Cr ) nonadditivity effects of the SO and electron correlation can be observed requiring a consistent treatment of both contributions.