Azomethines with Long Alkyl Chains: Synthesis, Characterization, Biological Properties and logP Modelling

The search of new antibacterial agents is an important task due to the emergence of resistance to widely used drugs. The bromine, chlorine and nitro-substituted in phenyl ring azomethines with long alkyl chains (C12, C14, C16 and C18) were synthesized and characterized by several experimental methods (NMR and IR spectroscopy, elemental analysis). Antibacterial activity was tested on several cultures and the synthesized compounds show the activity at the level of some commercial antiseptics. Lipophilicity (which is important descriptor for biological properties prediction) of the experimentally synthesized and isomeric molecules was determined by three different approaches: quantum chemistry, machine learning (GraphormerLogP model) and atom contribution model (RDKit library). Quantum-chemical method can take into account any spatial arrangements and can be considered the most accurate of the used approaches, but a lot of computational time it is necessary for it. Atom contribution model is the fastest of the used methods but gives underestimated results and different isomers have exactly the same values in contrast to the quantum chemistry results. Machine learning-based methods (GraphormerLogP) demonstrate acceptable accuracy, sensitivity to isomerism, and orders of magnitude higher throughput, making them an optimal tool for high-throughput screening.