A QSAR Study on the 4-Substituted Coumarins as Potent Tubulin Polymerization Inhibitors.

Purpose: Despite the discovery and synthesis of several anticancer drugs, cancer is still a major life threatening incident for human beings after cardiovascular diseases. Toxicity, severe side effects, and drug resistance are serious problems of available commercial anticancer drugs. Coumarins are synthetic and natural heterocycles that show promising antiproliferative activities against various tumors. The aim of this research is to computationally study the coumarin derivatives in order to develop reliable quantitative structure-activity relationship (QSAR) models for predicting their anticancer activities. Methods: A data set of thirty one coumarin analogs with significant antiproliferative activities toward HepG2 cells were selected from the literature. The molecular descriptors for these compounds were calculated using Dragon, HyperChem, and ACD/Labs programs. Genetic algorithm (GA) accompanied by multiple linear regression (MLR) for simultaneous feature selection and model development was employed for generating the QSAR models. Results: Based on the obtained results, the developed linear QSAR models with three and four descriptors showed good predictive power with r2 values of 0.670 and 0.692, respectively. Moreover, the calculated validation parameters for the models confirmed the reliability of the QSAR models. Conclusion: The findings of the current study could be useful for the design and synthesis of novel anticancer drugs based on coumarin structure.

Triterpenoid corosolic acid attenuates HIF-1 stabilization upon cobalt (II) chloride-induced hypoxia in A549 human lung epithelial cancer cells.

Hypoxia-inducible factor-1 is a target for the management of cancer. Here, the anti-proliferation properties of corosolic acid (CA) against A549 human lung epithelial cancer cells in CoCl2-induced hypoxia is reported. CA was isolated from the roots of Salvia syriaca based on a bioassay-guided isolation platform and identified by 1D and 2D NMR experiments. Several cytotoxicies and genotoxicity analyses were performed using MTT, DAPI, cell cycle, DNA ladder, and annexin V/PI detection. Cobalt chloride (CoCl2) was used to stimulate hypoxia. The adaptation of A549 cells to a stimulated hypoxic condition in the presence of CA was evaluated. CA decreased the growth of A549 cells with an IC50 of 12 µg/mL at 48 h. Also, chromatin condensation and DNA fragmentation were detected as signs of apoptosis occurrence. CA induced ~85% apoptosis and even 1% necrosis. The expression of hypoxia-inducible factor-1 α (HIF-1α), HIF-1ß and downstream genes was strongly suppressed in the presence of CA in CoCl2-stimulated hypoxia condition. Results indicated that CA has remarkable cytotoxicity against the cancerous cell in hypoxia condition and may be regarded for preparation of new formulations for possible uses as supplement and medicine in cancer therapy.

The selective adsorption of formaldehyde and methanol over Al- or Si-decorated graphene oxide: A DFT study.

Density functional theory (DFT) calculations are performed to study the adsorption behavior of formaldehyde and methanol on the pristine as well as Al- or Si-decorated graphene oxide (GO). The most stable adsorption configurations, adsorption energies, binding distances and net charge transfers are obtained to understand the impacts of the these molecules on the electronic properties of the pristine or metal-decorated GO surface. The pristine GO exhibits a low sensitivity to both formaldehyde and methanol molecules. However, it is found that the decoration of GO with a Al or Si atom enhances its tendency to adsorb both the above gas molecules. Compared to formaldehyde, methanol is found to have a larger adsorption energy over the decorated GOs, due to the more favorable orbital interaction as well as electrostatic attraction in the resulted complexes. The amounts of charge transfer upon adsorption of formaldehyde and methanol over the Al-decorated GO are larger than those of over the Si-decorated one. Therefore, as a result of interaction with CH2O and CH3OH, the electronic properties of the Al-decorated GO change significantly.

Catalytic hydrogenation of CO2 over Pt- and Ni-doped graphene: A comparative DFT study.

Today, the global greenhouse effect of carbon dioxide (CO2) is a serious environmental problem. Therefore, developing efficient methods for CO2 capturing and conversion to valuable chemicals is a great challenge. The aim of the present study is to investigate the catalytic activity of Pt- or Ni-doped graphene for the hydrogenation of CO2 by a hydrogen molecule. To gain a deeper insight into the catalytic mechanism of this reaction, the reliable density functional theory calculations are performed. The adsorption energies, geometric parameters, reaction barriers, and thermodynamic properties are calculated using the M06-2X density functional. Two reaction mechanisms are proposed for the hydrogenation of CO2. In the bimolecular mechanism, the reaction proceeds in two steps, initiating by the co-adsorption of CO2 and H2 molecules over the surface, followed by the formation of a OCOH intermediate by the transfer of H atom of H2 toward O atom of CO2. In the next step, formic acid is produced as a favorable product with the formation of CH bond. In our proposed termolecular mechanism, however, H2 molecule is directly activated by the two pre-adsorbed CO2 molecules. The predicted activation energy for the formation of the OCOH intermediate in the bimolecular mechanism is 20.8 and 47.9kcalmol-1 over Pt- and Ni-doped graphene, respectively. On the contrary, the formation of the first formic acid in the termolecular mechanism is found as the rate-determining step over these surfaces, with an activation energy of 28.8 and 45.5kcal/mol. Our findings demonstrate that compared to the Ni-doped graphene, the Pt-doped surface has a relatively higher catalytic activity towards the CO2 reduction. These theoretical results could be useful in practical applications for removal and transformation of CO2 to value-added chemical products.

The Genus Heracleum: A Comprehensive Review on Its Phytochemistry, Pharmacology, and Ethnobotanical Values as a Useful Herb.

Heracleum species, also known as hogweed, are traditionally used as food additives, spices, and flavoring agents. Moreover, these plants are widely used in folklore medicine for the treatment of many disorders such as inflammation, flatulence, stomachache, epilepsy, psoriasis, and as carminative, wound healing, antiseptic, antidiarrheal, tonic, digestive, pain killer, analgesic, and anticonvulsant agents. The genus Heracleum has broad pharmacological activities: anti-inflammatory, antimicrobial, anticholinesterase, anti-oxidant, antiviral, cytotoxic, and anticarcinogenic. A total of 94 compounds have been isolated from plants of the Heracleum genus, all indicating vital biological activities. Also, about 50 compounds have been identified as major components in their essential oils. The genus is rich in several types of bioactive coumarin compounds, with huge potential for the discovery of new coumarins. Various parts of these plants produce essential oils (mainly aliphatic esters and monoterpenes) with a wide spectrum of biological activities. Heracleum species have great potential for applications in the food, cosmetics, perfumery, and pharmaceutical industries due to their broad ethnobotanical uses and pharmacological properties. Accordingly, this review aims to categorize updated and comprehensive information on ethnobotanical uses, phytochemistry, and pharmacology of Heracleum species in order to open new perspectives for future studies, including possible uses as functional ingredients in food products.