In-silico discovery of efficient second-generation drug derivatives with enhanced antihistamine potency and selectivity
Abstract
The current study focuses on the potential of second-generation antihistamines, which exhibit fewer side effects compared to first-generation drugs, to block the Histamine H1 receptor (H1R) and mitigate allergic responses. We screened several derivatives of second-generation drugs taking Desloratadine (Deslo) and Acrivastine (Acra) as seed compounds. We performed molecular docking, drug-likeness, quantum chemical calculations, UV-visible and infrared spectroscopy, molecular electrostatic potential (MEP) mapping for understanding drug derivatives potential as efficient drugs and molecular dynamics (MD). The results depicted that among all Deslo1 showed best binding energy of -8.6 kcal/mol and best inhibition constant too. Moreover, LEU157 formed a conventional hydrogen bond with a ligand at distance of 2.51 Å in Deslo1. Deslo2 showed 95.2 % intestinal absorption which is quite good. None of the drugs showed any toxicity. The residues from catalytic site like Phe 116, Leu 154 and Leu 157 showed reasonably small fluctuations owing to their interactions with respective ligands. The RMSDs of Acra1 and Deslo2 mostly stay within 1Å range. For MD simulations best docked compounds (Acra1, Acra2, Deslo1 and Deslo2) were chosen and carried for 120 ns (120 ×106 fs). MD simulations trajectory is analyzed for the assessment of some important parameters like RMSD, RMSF, SASA, and RG. Moreover, ADMET analysis are performed to confirm their drug-like properties. The molecular geometries of…
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