Novel 2-aryl-4-aryloxyquinoline-based fungistatics for Mucor circinelloides. Biological evaluation of activity, QSAR and docking study.

Zygomycetes are ubiquitous saprophytes in natural environments which transform organic matter. Some zygomycetes of gender Mucor have attracted interest in health sector. Due to its ability as opportunistic microorganisms infecting immuno-compromised people and to the few available pharmacological treatments, the mucormycosis is receiving worldwide attention. Concerning to the pharmacological treatments, some triazole-based compounds such as fluconazole are extensively used. Nevertheless, we focused in the quinolines since they are broadly used models for the design and development of new synthetic antifungal agents. In this study, the fungistatic activity on M. circinelloides of various 2-aryl-4-aryloxyquinoline-based compounds was discovered, and in some cases, it resulted better than reference compound fluconazole. These quinoline derivatives were synthesized via the Csp2-O bond formation using diaryliodonium(III) salts chemistry. A QSAR study was carried out to quantitatively correlate the chemical structure of the tested compounds with their biological activity. Also, a docking study to identify a plausible action target of our more active quinolines was carried out. The results highlighted an increased activity with the fluorine- and nitro-containing derivatives. In light of the few mucormycosis pharmacological treatments, herein we present some non-described molecules with excellent in vitro activities and potential use in the mucormycosis treatment.

Derivates of 1,6-dihyadroazaazulenes as inhibitors of tyrosine kinases BCR-ABL1 wild type and mutant T315I: a molecular dynamics approach.

The protein tyrosine kinase (PTK) produced by the BCR-ABL1 gene has generated significant interest in the development of inhibitors since the presence of punctual mutations causes resistance to currently approved drugs, mainly the T315I mutation has been the most difficult to address. In this work, derivatives of 1,6-dihydroazaazulenes are studied as possible inhibitors of this PTK in its wild form and the mutant T315I. The recognition of the ligands was explored through molecular docking, and the stability of the complexes and their evolution over time was studied using molecular dynamics (MD) simulations. Our results show that complexes are energetically stable and reside on the ATP binding site in all cases during the MD experiments. Interestingly, a few of our proposed ligands presented greater affinity for T315I, finding more favorable binding free energies (ΔG) than the reference drug axitinib. Furthermore, they may act as inhibitors for both isoforms. Our findings are promising because mutation of T315I does not prevent ligand recognition, as detailed in this work, which is very important to conduct further experimental research.Communicated by Ramaswamy H. Sarma.

Oxidative amidation of benzaldehyde using a quinone/DMSO system as the oxidizing agent.

An efficient transition-metal-based heterogeneous catalyst free procedure for obtaining the oxidative amidation of benzaldehyde using quinones as oxidizing agents in low molar proportions is described here. Pyrrolylquinones (PQ) proved to be more suitable than DDQ and 2,5-dimethylbenzoquinone to conduct the oxidation process. Although the solvent itself acted as the oxidant with low to moderate yields, PQ/DMSO provided an efficient system for carrying out the reaction under operational simplicity, mild reaction conditions, short reaction times and high yields of the desired product. The scope of the method was evaluated with substituted benzaldehydes and secondary amines. Theoretical foundations are given to explain the participation of quinones as an oxidizing agent in the reaction.