Synthesis and biological evaluation of new 3-amino-2-azetidinone derivatives as anticolorectal cancer agents

Several synthetic combretastatin A4 (CA-4) derivatives were recently prepared to increase the drug efficacy and stability of the natural product isolated from the South African tree Combretum caffrum. A group of ten 3-amino-2-azetidinone derivatives, as combretastatin A4 analogues, was selected through docking experiments, synthesized and tested for their anti-proliferative activity against the colon cancer SW48 cell line. These molecules, through the formation of amide bonds in position 3, allow the synthesis of various derivatives that can modulate the activity with great resistance to hydrolytic conditions. The cyclization to obtain the 3-aminoazetidinone ring is highly diastereoselective and provides a trans biologically active isomer under mild reaction conditions with better yields than the 3-hydroxy-2-azetidinone synthesis. All compounds showed IC50 values ranging between 14.0 and 564.2 nM, and the most active compound showed inhibitory activity against tubulin polymerization in vitro, being a potential therapeutic agent against colon cancer

Alcohol and 1,2-diol dehydrogenases : synthetic use as oxidants

The redox equilibrium between alcohol - carbonyl groups is greatly used by enzymes and chemists to prepare useful compounds. Carbonyls are often intermediate groups whose reactivity can be used to synthesize complex Structures: in contrast, alcohols are more easily found in the products of interest because their coordinative ability is used both in biology and in chemistry. Dehydrogenase activities are an interesting alternative to chemical redox reactants because they are often chemo-. regio-. and stereo-selective. These enzymes allow for two different uses: direct, as racemates resolving agents-, inverse. as enantioselective reducing agents. We will focus on their use as oxidative agents. considering both the well-known alcohol dehydrogenases and the less known and less used 1,2-diol dehydrogenases. An account of both classes will be presented

Quantitative aquatic toxicity prediction: using group contribution and classification methods on polar and non-polar narcotics

A model based on a Group Contribution Method (GCM) approach developed to correlate aquatic toxicity to fathead minnow (Pimephales promelas) has been applied to an external set containing 190 organic chemicals. This set was also previously partitioned into polar and non-polar toxicants using a different classification model. The application of the GCM approach to develop specific models both of the entire set and of its partitions permits to discuss the importance of the subclassification in order to improve the result

Predicting toxicity : a mechanism of action model of chemical mutagenicity

The increasing importance of theoretical studies for predicting toxicology has aroused the interest of many computational chemists. A new approach has been developed, based on studying at the molecular level two potential mechanisms of action that are related to compound mutagenicity. This approach is the first example that considers both the toxicant and the biological target molecules involved in the interaction. Using some calculated descriptors and a simulation of the interaction chemical, compounds can be classified. More important, the approach helps in understanding and explaining both the correct and the incorrect results, and gives a deeper understanding of the toxic mechanisms. The model has been applied to many compounds and the results are compared with experimental results reported for the corresponding Salmonella tests

Analysis of a Theoretical Model Based on Similarity for Studying RNA Base Pairings

A theoretical model for studying RNA base pairing is presented, based on similarity measures of the bases and corresponding indexes. Similarity calculations are made by evaluating atomic importance in molecules, a method that uses an original method for the calculation of electronic energy. The application of the model to both Watson-Crick and non-Watson-Crick pairings is commented on. Some theoretical considerations concerning the capability of the genetic code to repair dangerous mutations contribute to the ongoing debate

Electrocatalytic potentialities of silver as a cathode for organic halide reductions

The peculiar halide affinity for silver results in an extraordinary electrocatalytic activity for the redn. of halides (either glycosyl halides or, more generally, aryl and alkyl halides). The most striking features are: (a) a redn. potential shift in the pos. direction of 3c1000 mV with respect to glassy carbon and 500 mV with respect to mercury; (b) a cage effect, evidenced in previous synthetic work concerning bromosugars, promoted by the halide acting as a bridge between the electrode surface and the reacting substrate, which mainly results in dimerization and/or addn. products. The above electrocatalytic effect is here studied by a systematic reactivity study on Ag, Hg and glassy carbon cathodes, with a variety of substrates. The effect of the supporting electrolyte is also analyzed in detail, providing a 1st inspection on specific halide/silver interactions in acetonitrile media

Glycosyl halides as building blocks for the electrosynthesis of glycosides

The importance and variety of glycosides in nature together with the lack of a conclusive synthetic methodol. prompted study of the electrochem. reductive behavior of glycosyl halides to generate suitable intermediates for the glycosidation of both aliph. and arom. acceptors. A special case, here considered, is the almost quant. synthesis of C-C glycosyl dimer