Anti-enzymatic and DNA docking studies of montelukast: A multifaceted molecular scaffold with investigations, molecular expression analysis and molecular dynamics simulations.

Montelukast, an approved leukotriene receptor 1 (Cys-LT 1) antagonist with anti-inflammatory properties is used for the treatment of asthma and allergic rhinitis. In the present studies, montelukast was subjected to inhibitory assays followed by kinetic and investigations. Montelukast demonstrated inhibitory activity against yeast α-glucosidase (IC 44.31 ± 1.21 μM), jack bean urease (JB urease, IC 8.72 ± 0.23 μM), human placental alkaline phosphatase (hPAP, IC 17.53 ± 0.19 μM), bovine intestinal alkaline phosphatase (bIAP, IC 15.18 ± 0.23 μM) and soybean 15-lipoxygenase (15-LOX, IC 2.41 ± 0.13 μM). Kinetic studies against α-glucosidase and urease enzymes revealed its competitive mode of inhibition. Molecular expression analysis of montelukast in breast cancer cell line MCF-7 down-regulated AP by a factor of 0.27 (5 μM) compared with the 0.26 value for standard inhibitor levamisole (10 μM). Molecular docking estimated a binding affinity ranging -8.82 to -15.65 kcal/mol for the enzymes. Docking against the DNA dodecamer (ID: 1BNA) observed -9.13 kcal/mol via minor groove binding. MD simulations suggested stable binding between montelukast and the target proteins predicting strong inhibitory potential of the ligand. Montelukast features a chloroquinoline, phenyl ring, a cyclopropane group, a carboxylic group and a sulfur atom all of which collectively enhance its inhibitory potential against the said enzymes. These and computational investigations demonstrate that it is possible and suggested that the interactions of montelukast with more than one targets presented herein may be linked with the side effects presented by this drug and necessitate additional work. The results altogether suggest montelukast as an important structural scaffold possessing multitargeted features and warrant further investigations in repurposing beyond its traditional pharmacological use.