HIV-1 integrase is an extremely important nominee in developing new and effective drugs especially naphthyridine compounds against acquired immune deficiency syndrome. The quantitative structure-activity relationship (QSAR) modeling is the most powerful method in computer-aided drug design and will be used to help the design of new naphthyridine derivatives. Different computational 2D-QSAR procedures applied to predict the relationship between the computational descriptors of naphthyridine derivatives with their HIV-1 integrase inhibition activities. Four different models including stepwise-MLR, consensus stepwise-MLR, GAPLS-MLR, and consensus GAPLS-MLR with appropriate correlation between the calculated and experimental biological activities (pIC 50 ) against HIV-1 integrase were generated. Predictive QSAR models were obtained with R training 2 values of 0.848, 0.862, 0.709, and 0.751 as well as R test 2 values of 0.521, 0.651, 0.502, and 0.775 for stepwise-MLR, consensus stepwise-MLR, GAPLS-MLR, and consensus GAPLS-MLR models, respectively. QSAR models are high efficiency in prediction of the pIC 50 in comparison with other models because of concerning the combination of ''quantum and molecular mechanical'' descriptors. Combination of ''quantum'' and ''molecular mechanical'' descriptors improved our models with high efficient test set activity prediction potency. The obtained results provided useful information for understanding the effects of polarizability, electronegativity, and especially functional groups such as aromatic nitrogens that are important for the activities of naphthyridine compounds. The developed QSAR models will be efficient for the rational design of potent naphthyridine derivatives against HIV-1 integrase activity.
One of the most active areas within the field of bioorganometallic chemistry, complexes of N-heterocyclic carbenes (NHCs), have recently gained interest. Herein, we report two luminescent palladium N-heterocyclic carbene complexes; namely [Pd {(C,N)-C 6 H 4 CH 2 NH(CH 2 CH 3 )}(1)] (2) and [Pd{(C,N)-C 6 H 4 CH 2 NH 2 }(1)] (3) (1 = 1-methyl-3-(2-oxo-2-(pyren-1-yl)ethyl)-2,3-dihydroimidazol-2-ylidene) which were synthesized from the reaction of luminescent imidazolium salt (1(H)Br) and binuclear Palladacycles. The interactions of them with CT-DNA evaluated via absorption, emission and CD spectral techniques as well as measurements of viscosity and thermal denaturation and the results have been shown that they bounded to CT-DNA by intercalation and groove binding modes. The in vitro cytotox-icity of compounds 2-3 and 1(H)Br on human breast (MCF-7) and cervical epithelial carcinoma (HeLa) cancer cells lines, indicated the wide range of anticancer activities of them with low IC 50 values. Moreover, based on the protein binding ability studies, the intrinsic fluorescence of BSA could be strongly quenched by compounds via a static quenching mechanism. Competitive binding study using Eosin, Digoxin and Ibuprofen as site markers, indicated that the compounds could bind to sites I and II on BSA structure. Finally, all data obtained from biophysical studies were validated by molecular modeling study. Computational results showed that palladium complexes have the potential for detection of mismatch DNA.
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