Current Chemical Biology Deepika Godugu, Karuna Rupula and Beedu S. Rao * Department of Biochemistry, University College of Science, Osmania University, Hyderabad-500 007, Telangana Abstract: Background: Forskolin, a polyhydroxylated labdone diterpene possesses various medicinal properties in the treatment of chronic diseases, in humans. The present study aimed to evaluate the interaction and binding affinity between forskolin and HSA by in silico method and spectral analysis. Methods: The in silico study for screening the interaction of forskolin with HSA protein was carried out using AutoDock Vina software. The evaluation and characterization of the HSA–forskolin complex formation was achieved by spectroscopic methods–UV absorption, HPLC and FTIR analysis. Results: The in silico studies revealed that forskolin mainly binds on site II A and III A of HSA, with binding score -7.4 kcal mol -1 and formations of hydrogen bonds with amino acid residues Asn 295, Arg 218 and Pro 447. The UV spectral analysis revealed the λ max for forskolin at 210 nm, for HSA at 220 & 280 nm, and for HSA bound forskolin at 215 nm indicating the formation of HSA-forskolin complex. A new peak was observed at retention time 0.787 min by HPLC analysis. The Bmax was found to be at 34 ± 0.12 mg protein and Kd value was 5.3x10 -11 ± 0.03 M indicating interaction of forskolin with HSA. The FTIR analysis demonstrated shifting of amide I groups from 1600, 1640 to 1596, 1636 cm −1 respectively further establishing the binding of forskolin to HSA. Conclusion: The study demonstrates the binding of forskolin to HSA and formation of HSA-forskolin complex. We further hypothesize the imperative role of HSA in the pharmacokinetics of forskolin. A R T I C L E H I S T O R Y Received: July 3, 2016 Revised: September 11, 2016 Accepted: September 23, 2016 DOI: 10.2174/22127968106661609261611 27 Keywords: Forskolin; human serum albumin; HSA-forskolin complex; forskolin binding. INTRODUCTION The pharmacokinetics of a drug administered is influenced by the transport mechanisms, and its solubility (water/lipid soluble). The transport mechanisms are either by direct passage of drugs across cell membranes or via selective carrier mediated system. The effectiveness of drugs as pharmaceutical / therapeutic agents depends on their binding ability to carrier proteins and has engrossed an interesting area of research in pharmacology [1]. The drug-carrier protein *Address correspondence to this author at the Department of Biochemistry, University College of Science, Osmania University, Hyderabad - 500 007, Telangana, India; Tel: 091 040 2709 7044; E- mail: sashi_rao@yahoo.com interactions play crucial role in the ADME properties of the drug. Two major types of circulatory proteins BSA and HSA act as the carrier/transport proteins in drug metabolism. Human serum albumin (HSA) is the major plasma protein which accounts for about 60% of the total plasma proteins and is equivalent to a concentration of 42 mg mL -1 [2]. The HSA proteins plays a major role in the maintenance of pH, colloid osmotic pressure of the blood and also in the absorption, distribution, metabolism and excretion of several endogenous and exogenous substances such as fatty acids, nutrients, steroids, metal ions, hormones, enzymes, surfactants and a number of therapeutic drugs. Most drugs circulate in plasma and reach the target tissues by binding to 1872-3136/16 $58.00+.00 © 2016 Bentham Science Publishers Send Orders for Reprints to reprints@benthamscience.ae Current Chemical Biology, 2016, 10, 127-134 127 RESEARCH ARTICLE Binding Interactions of Forskolin with Human Serum Albumin: Insights from In silico and Spectroscopic Studies