Synthesis, docking, QSAR, ADMET and antimicrobial evaluation of new quinoline-3-carbonitrile derivatives as potential DNA-gyrase inhibitors

摘要

Novel sixty three quinoline-3-carbonitrile derivatives were synthesized starting from 6-substituted-2-hydrazinyl quinoline-3-carbonitrile. The synthesized compounds were characterized by IR, H-1 NMR,C- 13 NMR and mass spectroscopy. Some compounds were evaluated for their antibacterial and antifungal activities using agar diffusion technique. The compounds exhibited higher inhibition zones were further tested to determine their minimum inhibitory concentrations (MIC) using a serial dilution technique. The results revealed that compounds 7(a), 7(g), 7(i), 7(l) and 7(o) have promising antimicrobial activities with MIC ranging from 12.5 to 25 mu g/mL. Furthermore, molecular docking studies were performed to investigate binding patterns of the synthesized compounds against DNA-gyrase (PDB: 2xct), using Accelrys Discovery studio 2.5 software. Moreover, a QSAR model was generated to explore the structural requirements controlling antimicrobial activities of the synthesized compounds against Bacillus subtilis. The synthesized compounds were analyzed for their ADMET properties. Results revealed the synthesized compounds have low ability to penetrate BBB, good to moderate aqueous solubility and non-inhibitory effect against CYP2D6. (C) 2018 Published by Elsevier B.V.