The Ability of Chlorophyll to Trap Carcinogen Aflatoxin B1: A Theoretical Approach.

The coordination of one and two aflatoxin B1 (AFB1, a potent carcinogen) molecules with chlorophyll a (chl a) was studied at a theoretical level. Calculations were performed using the M06-2X method in conjunction with the 6-311G(d,p) basis set, in both gas and water phases. The molecular electrostatic potential map shows the chemical activity of various sites of the AFB1 and chl a molecules. The energy difference between molecular orbitals of AFB1 and chl a allowed for the establishment of an intermolecular interaction. A charge transfer from AFB1 to the central cation of chl a was shown. The energies of the optimized structures for chl a show two configurations, unfolded and folded, with a difference of 15.41 kcal/mol. Chl a appeared axially coordinated to the plane (α-down or ß-up) of the porphyrin moiety, either with the oxygen atom of the ketonic group, or with the oxygen atom of the lactone moiety of AFB1. The complexes of maximum stability were chl a 1-α-E-AFB1 and chl a 2-ß-E-AFB1, at -36.4 and -39.2 kcal/mol, respectively. Additionally, with two AFB1 molecules were chl a 1-D-2AFB1 and chl a 2-E-2AFB1, at -60.0 and -64.8 kcal/mol, respectively. Finally, biosorbents containing chlorophyll could improve AFB1 adsorption.

In vitro and computational studies of natural products related to perezone as anti-neoplastic agents.

Many natural phyto-products as perezone (Per) exhibit anti-cancer activities. Using experimental and computational studies, it was described that Poly ADP-ribose polymerase 1(PARP-1) inhibition and the induction of oxidative stress state explain the pro-apoptotic activity of Per. The aim of this study was to evaluate two phyto-products related to Per as anti-cancer agents: hydroxyperezone (OHPer) and its monoangelate (OHPer-MAng). These molecules were structurally characterized employing thermal analysis, IR spectrophotometry and X-ray diffraction techniques. The phyto-compounds evaluated in vitro in six cancer cell lines (K562, MCF-7, MDA-MB-231, HeLa, U373, A549) and non-malignant cells determinate their cytotoxicity, type of induced cell death, ability to avoid cell migration and changes at the redox status of the cell. Using, in vitro and computational studies provided the inhibition of PARP-1 and its potential binding mode. Cell proliferation assays demonstrated that OHPer-MAng treatment significantly induces apoptosis in triple negative breast cancer (TNBC) cell line (MDA-MB-231 IC50 = 3.53 µM), being particularly less cytotoxic to Vero cells (IC50 = 313.92 µM), human lymphocytes (IC50 = 221.46 µM) and rat endothelial cells (IC50=> 400 µM). The treatment of MDA-MB-231 cells with OHPer-MAng showed inhibition of migration by cancer cells. The induction of an oxidative stress state, similar to other quinones and PARP-1 inhibition explains the pro-apoptotic activity of OHPer-MAng. Docking studies showed that OHPer-MAng establishes great non-bonding interactions with the lateral chains of Tyr235, Hys201, Tyr246, Ser203, Asn207, and Gly233 located at the catalytic site of PARP-1, also demonstrating the anti-cancer activity of OHPer-MAng in TNBC cell line.

In silico Study of the Pharmacologic Properties and Cytotoxicity Pathways in Cancer Cells of Various Indolylquinone Analogues of Perezone.

Several indolylquinone analogues of perezone, a natural sesquiterpene quinone, were characterized in this work by theoretical methods. In addition, some physicochemical, toxicological and metabolic properties were predicted using bioinformatics software. The predicted physicochemical properties are in agreement with the solubility and cLogP values, the penetration across the cell membrane, and absorption values, as well as with a possible apoptosis-activated mechanism of cytotoxic action. The toxicological predictions suggest no mutagenic, tumorigenic or reproductive effects of the four target molecules. Complementarily, the results of a performed docking study show high scoring values and hydrogen bonding values in agreement with the cytotoxicity IC50 value ranking, i.e: indolylmenadione > indolylperezone > indolylplumbagine > indolylisoperezone. Consequently, it is possible to suggest an appropriate apoptotic pathway for each compound. Finally, potential metabolic pathways of the molecules were proposed.