Investigation of Interaction between NSAIDS and Antihypertensive Drugs using Computational Techniques

Abstract

In the current work, interaction studies of five Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and four Angiotensin Converting enzyme (ACE) enzyme amino acids with the antihypertensive drug, Lisinopril have been carried out on the molecular level using Quantum Mechanical Molecular Orbital Calculations with Density Functional Theory (DFT) and Hartree-Fock (HF) method using 6-31G basis set. Investigation of interactions was conducted with the aim of observing the comparative pharmacodynamics interaction studies of NSAIDs and amino acids with Lisinopril by scrutinizing the changes in geometric and electronic parameters of NSAIDs and amino acids of before and after complex formation with Lisinopril. Geometric parameter revealed increased electronic charge distribution on NSAIDs as compared to amino acids when interacted with lisinopril. Electronic parameters gave a measure of electron donating and electron accepting character of Lisinopril. Both geometric and electronic parameter revealed that electrostatic attraction and hence complex formation of NSAIDs with lisinopril is stronger as compared to that with amino acids. So in a competitive reaction NSAIDs complex formation is more favorable. According to the band gap value of ƐHOMO (lisinopril) - ƐLUMO (NSAIDs) lowest value of band gap is for aspirin which showed highest probability of electron transfer from lisinopril to aspirin as compared to other NSAIDs. This confirmed the formation of most strong charge transfer complex formation of aspirin-lisinopril and distortion of lisinopril leading to decrease in its antihypertensive effect. It was also observed that ƐLUMO of aspirin-lisinopril complex becomes more negative thus showing increased stability of aspirin-lisinopril complex. This investigation ultimately leads to reveal the drug interactions caused by NSAIDs in hypertension patients and suggests that aspirin should not be prescribed with Lisinopril. Decrease in antihypertensive effect of antihypertensive drugs by NSAIDs was also supported by discrete modeling, an approach of system biology.