Molecular docking and experimental investigation of new indole derivative cyclooxygenase inhibitor to probe its binding mechanism with bovine serum albumin

Tanveer A Wani; Ahmed H Bakheit; Seema Zargar; Mashooq A Bhat; Abdulrahman A Al-Majed

doi:10.1016/j.bioorg.2019.103010

Molecular docking and experimental investigation of new indole derivative cyclooxygenase inhibitor to probe its binding mechanism with bovine serum albumin

Bioorg Chem. 2019 Aug:89:103010. doi: 10.1016/j.bioorg.2019.103010. Epub 2019 May 22.

Authors

Tanveer A Wani¹, Ahmed H Bakheit², Seema Zargar³, Mashooq A Bhat⁴, Abdulrahman A Al-Majed⁴

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: twani@ksu.edu.sa.
² Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Chemistry, Faculty of Science and Technology, Al-Neelain University, Khartoum, Sudan.
³ Department of Biochemistry, College of Science, King Saud University, PO Box 22452, Riyadh 11451, Saudi Arabia.
⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

PMID: 31132602
DOI: 10.1016/j.bioorg.2019.103010

Abstract

The indole derivative 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene]acetohydrazide (IND) was synthesized for its therapeutic potential to inhibit cyclooxygenase (COX)-II. Binding if IND to bovine serum albumin (BSA) was investigated was because most drugs bind to serum albumin in-vivo. Fluorescence, UV-vis spectrophotometry and molecular modeling methodologies were employed for studying the interaction mechanism. The intrinsic fluorescence of BSA was quenched by BSA and the quenching mechanism involved was static quenching. The binding constants between IND and BSA at the three studied temperatures (298, 301 and 306 K) were 1.09 × 10⁵, 4.36 × 10⁴ and 1.23 × 10⁴ L mol^-1 respectively. The most likely site for binding IND to BSA was Site I (subdomain IIA). The analysis of thermodynamic parameter revealed the involvement of hydrogen bonding and van der Waals forces in the IND-BSA interaction. Synchronous fluorescence spectroscopic (SFS) and UV-vis spectrophotometric studies suggested conformational change in BSA molecule post interaction to IND. Molecular docking and the experimental results corroborated one another. The study can prove as an insight for future IND drug development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites / drug effects
Cattle
Cyclooxygenase 2 Inhibitors / chemical synthesis
Cyclooxygenase 2 Inhibitors / chemistry
Cyclooxygenase 2 Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Hydrazines / chemical synthesis
Hydrazines / chemistry
Hydrazines / pharmacology*
Indoles / chemical synthesis
Indoles / chemistry
Indoles / pharmacology*
Molecular Docking Simulation*
Molecular Structure
Serum Albumin, Bovine / chemistry*
Structure-Activity Relationship
Thermodynamics

Substances

Cyclooxygenase 2 Inhibitors
Hydrazines
Indoles
Serum Albumin, Bovine
indole
acetylhydrazine