A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins

• Published in: PloS one 2016-07, Vol.11 (7), p.e0158833-e0158833
• Main Authors: Nusrat, Saima, Siddiqi, Mohammad Khursheed, Zaman, Masihuz, Zaidi, Nida, Ajmal, Mohammad Rehan, Alam, Parvez, Qadeer, Atiyatul, Abdelhameed, Ali Saber, Khan, Rizwan Hasan
• Format: Article
• Language: English
• Subjects: Acids; Albumins; Animals; Anti-inflammatory agents; Antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Binding; Binding sites; Biology and Life Sciences; Biotechnology; Cattle; Chemical bonds; Circulatory system; Complex formation; Complications and side effects; Computation; Computer applications; Computer Simulation; Dosage and administration; Drug interactions; Drugs; Fluorescence; Free energy; Glycoproteins; Health aspects; Humans; Hydrogen; Hydrogen bonding; Hydrogen bonds; Hydrophobicity; Inflammation; Interdisciplinary aspects; Investigations; Kinases; Masoprocol - chemistry; Masoprocol - pharmacokinetics; Medicine and Health Sciences; Metabolism; Metabolites; Models, Chemical; Molecular docking; Nordihydroguaiaretic acid; Pharmaceuticals; Physical chemistry; Physical Sciences; Physiological aspects; Protein Binding; Protein structure; Protein transport; Proteins; Secondary structure; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - metabolism; Spectrophotometry, Ultraviolet; Spectroscopy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158833

Exogenous drugs that are used as antidote against chemotheray, inflammation or viral infection, gets absorbed and interacts reversibly to the major serum transport protein i.e. albumins, upon entering the circulatory system. To have a structural guideline in the rational drug designing and in the synthesis of drugs with greater efficacy, the binding mechanism of an antineoplastic and anti-inflammatory drug Nordihydroguaiaretic acid (NDGA) with human and bovine serum albumins (HSA & BSA) were examined by spectroscopic and computational methods. NDGA binds to site II of HSA with binding constant (Kb) ~105 M-1 and free energy (ΔG) ~ -7.5 kcal.mol-1. It also binds at site II of BSA but with lesser binding affinity (Kb) ~105 M-1 and ΔG ~ -6.5 kcal.mol-1. The negative value of ΔG, ΔH and ΔS for both the albumins at three different temperatures confirmed that the complex formation process between albumins and NDGA is spontaneous and exothermic. Furthermore, hydrogen bonds and hydrophobic interactions are the main forces involved in complex formation of NDGA with both the albumins as evaluated from fluorescence and molecular docking results. Binding of NDGA to both the albumins alter the conformation and causes minor change in the secondary structure of proteins as indicated by the CD spectra.