In silico approach for the development of phenolic derivatives as potential anti-angiogenic agents against lysyl oxidase-like 2 enzyme

Abstract Background Lysyl oxidase-like 2 (LOXL2) has recently been explored as extremely pivotal protein involved in angiogenesis which results in metastasis of numerous types of cancers. Hence, LOXL2 is an exciting new target for drug development against tumor progression and its spread to distant organs. Newly synthesized derivatives of natural phenolic antioxidant guaiacol (T1 to T8) were evaluated for their potential as anti-angiogenic agents using in silico approach. The drug likeness properties and toxicity of the synthesized derivatives have also been determined. Active binding sites of LOXL2 protein were determined by online server DoGSiteScorer, and lead–target interactions and conformations of pose analysis were done by using AutoDock Vina and Discovery Studio 4.0. The GUSAR model was applied to find the toxicity and ADMET properties. On the other hand, the chemoinformatics prediction was also performed using online FAF Drug Server and Molinspiration online server. Results Lead molecules from T1 to T8 showed promising binding affinity values, especially T5 and T8 showed best fit in the binding pocket of target enzyme (binding energies − 7.9 and 8.0 kcal/Mol, respectively). The stability of docked complexes was further evaluated using molecular dynamic simulation studies using GROMACS force field, and both leads (T5 and T8) were found to be strongly bounded to the active binding sites. The ADMET results revealed that all experimental molecules were virtually nontoxic and showed compliance with rule of five. Conclusion The present work will further enable researchers to understand how computer-aided drug designing tools may help to expedite new drug discovery process in a minimum cost.