Theoretical characterization and biological activity investigation of indirubins, cyclin dependent kinases inhibitors.

Up to now, significant research efforts have been directed towards investigating indirubin and its derivatives as potential candidates for developing new compounds with multiple biological activities. In the present work, natural indirubin and numerous of its chemical derivatives referred to as indirubins have been investigated computationally using DFT method with the B3LYP/6-311 + G(d,p) level of theory, in order to reveal structure- biological activity relationship. We started with a structural properties description. Results analysis indicated that extra interaction sites were provided through the set of substitutions in compounds (1): Indirubin-3'-monoxime, (2): Indirubin-5-sulfonic acid, (3): 5-Nitro-indirubinoxime, (4): 5'-OH-5-nitro-indirubinoxime (AGM130), (5): 7-Bromo-5'-carboxyindirubin-3'-oxime, and (6): 7 BIO and consequently, extra hydrogen bonds may be formed with the active sites of molecular targets, such as GSK-3, CDKs, and Aurora kinases, as well as the aryl hydrocarbon receptor. Subsequently, to get more information on the electronic properties of indirubin and its analogues, HOMO, LUMO, Egap, and further electronic parameters were carried out. The indirubin derivatives showed an easier interaction with its environment than indirubin, the parent compound. The UV-Visible spectra of indirubin and compounds 1-6 were also produced using TD-DFT with B3LYP functional and 6-311 + G(2d,p) basis set. The relationship between absorption and chemical structure is discussed. Two phototoxic brominated compounds showed important absorption spectra modifications. It was also found that the main absorption bands of all compounds derived from π→π*(HOMO→LUMO) transitions.Communicated by Ramaswamy H. Sarma.

DFT evaluation of structural, electronic and variation properties for complex carbohydrates with biological interest.

The synthetic bicyclic bis(hemiacetals) compounds 1,5-pyranose-9,7-pyranoses, with a structural analogy to the bicyclic monosaccharide Bradyrhizose, have been described here based on a theoretical approach, using DFT calculations with the B3LYP functional combined with the 6-311 + G(d,p) basis set. First, we have performed a geometrical and electronic properties description of (1 R,9S), (1S,9S) and (1S,9R)-1,5-pyranose-9,7-pyranoses. Results analysis indicated that, slight differences in the three-dimensional orientations of their atoms lead to an enormous difference in chemical reactivity. Consequently, (1S,9S) and (1S,9R) isomers are predicted to be the most resembling the natural bradyrhizose in structural features. To enhance the performance of these two isomers, a set of modifications through functional groups attached to the reactive sites were determined by local reactivity descriptors. Subsequently, in order to get more information on the obtained derivatives for both isomers, HOMO, LUMO, Egap and four electronic parameters were calculated and compared. The substituted systems show a good performance in chemical reactivity than the unmodified parent compounds.Communicated by Ramaswamy H. Sarma.