Antiproliferative activity of new derivatives of pyrazino[1,2-a]benzimidazole: Integrated cell-based assay and computational studies with divalent magnesium, iron, and copper ions.

Magnesium, iron, and copper are three vital metals that play essential roles in cancer cell proliferation. This study aimed to evaluate the metal chelation of new derivatives of pyrazino[1,2-a]benzimidazole and investigate their antiproliferative properties. The density functional theory method has been employed to evaluate the complexation properties of new synthetic pyrazino[1,2-a]benzimidazole derivatives possessing the 4-OMe, 2,4-dimethyl, and 3,4,5-trimethoxy substitution on N-2 phenyl ring with divalent magnesium, iron, and copper. The free energies for the water-ligand exchange reactions were employed to investigate the thermodynamic stability, water exchange properties, and electronic properties in the gas phase. Natural population analysis was employed to estimate atomic partial charges, second-order interactions between the filled and vacant orbitals, and the occupancies of the metals' valence s, p, and d orbitals. Among pyrazino[1,2-a]benzimidazole derivatives, the 3,4,5-trimethoxy substituted pyrazino[1,2-a]benzimidazole shows better electron donor ability. This compound also reduced proliferation and increased the apoptosis of human glioblastoma cancer cells.

The rise of deep learning and transformations in bioactivity prediction power of molecular modeling tools.

The search and design for the better use of bioactive compounds are used in many experiments to best mimic compounds' functions in the human body. However, finding a cost-effective and timesaving approach is a top priority in different disciplines. Nowadays, artificial intelligence (AI) and particularly deep learning (DL) methods are widely applied to improve the precision and accuracy of models used in the drug discovery process. DL approaches have been used to provide more opportunities for a faster, efficient, cost-effective, and reliable computer-aided drug discovery. Moreover, the increasing biomedical data volume in areas, like genome sequences, medical images, protein structures, etc., has made data mining algorithms very important in finding novel compounds that could be drugs, uncovering or repurposing drugs and improving the area of genetic markers-based personalized medicine. Furthermore, deep neural networks (DNNs) have been demonstrated to outperform other techniques such as random forests and SVMs for QSAR studies and ligand-based virtual screening. Despite this, in QSAR studies, the quality of different data sources and potential experimental errors has greatly affected the accuracy of QSAR predictions. Therefore, further researches are still needed to improve the accuracy, selectivity, and sensitivity of the DL approach in building the best models of drug discovery.

Synthesis of highly functionalized organic compounds through Ugi post-transformations started from propiolic acids.

The Ugi four-component (Ugi-4CR) post-transformation reactions have emerged as a prominent tool to construct complex organic molecules utilizing readily available starting materials. Propiolic acid derivatives are promising choice of substrates due to their versatile reactivity. Over the last decade, Ugi post-transformations starting from propiolic acid derivatives have experienced a rapid growth to afford atom-efficient processes and enantioselective transformations. This review has focused on the recent advances in the Ugi post-transformations starting from propiolic acids and their application for the preparation of highly functionalized organic compounds.

A transition-metal-free fast track to flavones and 3-arylcoumarins.

A highly regioselective and transition-metal free one-pot arylation of chromenones with arylboronic acids has been achieved employing K2S2O8. The procedure consists of a sequence of some reactions including an arylation/decarboxylation cascade and proceeds well in aqueous media to afford biologically interesting flavones and 3-arylcoumarins. This method exhibited excellent selectivity and functional group tolerance under mild conditions. The reaction also showed perfect efficacy for the preparation of styryl coumarins.

Palladium/norbornene chemistry: an unexpected route to methanocarbazole derivatives via three Csp3-Csp2/Csp3-N/Csp2-N bond formations in a single synthetic sequence.

A Catellani reaction terminated by palladacycle amination leading to methanocarbazoles is reported. The outcome is the formation of three different Csp(3)-Csp(2)/Csp(3)-N/Csp(2)-N bonds through a Heck reaction/C-H activation/double amination cascade in one process.

Palladium-catalyzed decarboxylative cross-coupling reactions: a route for regioselective functionalization of coumarins.

A straightforward, regioselective, and step-economical ligand-free palladium-catalyzed decarboxylative functionalization of coumarin-3-carboxylic acids is devised. This protocol is compatible with a wide variety of electron-donating and -withdrawing substituents and allows for construction of various biologically important π-electron extended coumarins.