Binding and Anticancer Properties of Plumbagin with Human Serum Albumin

Abstract

Plumbagin has received extensive attention as a promising anticancer drug. Therefore, we investigated the binding and anticancer properties of plumbagin with human serum albumin. Fluorescence results demonstrated that plumbagin interacts with human serum albumin, although its binding affinity may be affected to various extents by different compounds. The human serum albumin-plumbagin complex structure revealed that plumbagin binds to the hydrophobic cavity in the IIA subdomain of human serum albumin through hydrogen bonding and hydrophobic interactions. The plumbagin-human serum albumin complex enhances cytotoxicity by 2- to 3-fold particularly in cancer cells but has no effect on normal cells in vitro. Compared with the unbound drug, the human serum albumin-plumbagin complex promotes HeLa cell apoptosis and has a stronger capacity for cell cycle arrest at the G2/M phase of HeLa cells. In conclusion, this study contributes to the rational design and development of plumbagin-based drugs and a drug-human serum albumin delivery system.

Strategies for Preparing Albumin-based Nanoparticles for Multifunctional Bioimaging and Drug Delivery

“…Albumin comprises hydrophobic pockets that facilitate its binding to hydrophobic or amphiphilic small molecules for effective delivery 165 - 168 . The binding between albumin and drugs/peptides could be achieved by direct interaction between albumin and drugs/peptide or interaction between albumin and prodrugs/peptide-conjugate.…”

Developing an Anticancer Copper(II) Pro-Drug Based on the His242 Residue of the Human Serum Albumin Carrier IIA Subdomain

“…HSA is a promising drug delivery system because it is nontoxic, nonantigenic, biocompatible and biodegradable, and nonimmunogenic. − Two commonly applied HSA-based drug delivery strategies include chemical coupling of drugs to form albumin–drug conjugates and encapsulation of drugs in albumin nanoparticles via physical interactions. − However, these two methods can introduce exogenous chemicals or change albumin’s conformation. To overcome drawbacks associated with HSA-based drug delivery strategies, we attempted a novel approach for developing HSA-based drug delivery by complexing an anticancer drug with HSA. − Preliminary data have shown that the HSA complex had greater anticancer activity and targeting ability than the drug alone. − Furthermore, current studies confirmed by X-ray crystallography revealed that metal (Ru and Cu) compounds can bind to the IIA subdomain of HSA via Lys199 and His242, replacing two ligands, and coordinating to the metal center. , Therefore, to synergize anticancer activity and targeting ability of metal agents in vivo , metal anticancer drugs that bind to the HSA IIA subdomain may be promising. − …”

Green Production of Indolylquinones, Derivatives of Perezone, and Related Molecules, Promising Antineoplastic Compounds

“…In particular, perezone or pipitzaoic acid, a sesquiterpene quinone, is recognized as the first secondary metabolite isolated in the New World by Río de la Loza [5], from the roots of Perezia (currently Acourtia) specimens; this important molecule has been the target of many chemical, structural, and biological studies, for example, its transformation into pipitzols [6][7][8] and isoperezone [9], its structural elucidation [10,11], several green contributions [12], its use as a pigment [13], and highlighting several pharmacological effects [14][15][16][17][18][19][20][21]. By the way, plumbagin, a naphthoquinone from the genus Plumbago [22,23], has been ascribed to several biological properties, for example, its antineoplasic activity [24].…”