title: A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins.
abstract: 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.
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh- 202002, India.
authors.forename: Saima
authors.initials: S
authors.lastname: Nusrat
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh- 202002, India.
authors.forename: Mohammad Khursheed
authors.initials: MK
authors.lastname: Siddiqi
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh- 202002, India.
authors.forename: Masihuz
authors.initials: M
authors.lastname: Zaman
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh- 202002, India.
authors.forename: Nida
authors.initials: N
authors.lastname: Zaidi
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh- 202002, India.
authors.forename: Mohammad Rehan
authors.initials: MR
authors.lastname: Ajmal
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh- 202002, India.
authors.forename: Parvez
authors.initials: P
authors.lastname: Alam
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh- 202002, India.
authors.forename: Atiyatul
authors.initials: A
authors.lastname: Qadeer
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
authors.forename: Ali Saber
authors.initials: AS
authors.lastname: Abdelhameed
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh- 202002, India.
authors.forename: Rizwan Hasan
authors.identifier: http://orcid.org/0000-0002-9965-8982
authors.initials: RH
authors.lastname: Khan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D002417:Cattle; D003198:Computer Simulation; D006801:Humans; D009637:Masoprocol / Q000737:chemistry* / Q000493:pharmacokinetics; D008956:Models, Chemical; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D012710:Serum Albumin, Bovine; D009637:Masoprocol