Paper
Molecular binding mechanism of 5-hydroxy-1-methylpiperidin-2-one with human serum albumin
Published Feb 17, 2018 · Sangilimuthu Alagar Yadav, D. P. Yeggoni, Elsinraju Devadasu
Journal of Biomolecular Structure and Dynamics
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Abstract
5-hydroxy-1-methylpiperidin-2-one (5-HMP) is a piperidine alkaloid found in various medicinal plants including seeds of Piper nigrum, Piper longum, fruit of Piper retrofractum and other medicinal plants such as Pinus ponderosa, aerial parts of Piper methysticum, stem bark of Microcos paniculata, Cassia leptophylla, rhizome of Arisaema decipiens and root of Lobelia laxiflora. This type of piperidine alkaloids reported against various diseases such as piperidine for cancer, piperamides and piperzine analogs for depressant, antioxidants, piperine for hypertensive and inflammatory problems, quinine for malarial disease, ephedrine for asthma, vincamine used as vasodilatory agent, piperine as antihyperglycemic agent. Also, 5-HMP from Tragia involucrata L. leaves for bronchoconstriction as antihistamine reported from the previous study and also aerial part of T. involucrata extracts reported against MCF-7 and KB cell line, methanol extract of T. involucrata root contains wound healing activity, T. involucrata extract possesses analgesic and anti-inflammatory (Alagar Yadav, Ramalingam, Jabamalai Raj, & Subban, 2015). Human serum albumin (HSA) is a major protein in blood plasma which contains excellent binding capacity for Ca, Na, K, hormones, bilirubin, zinc with metal binding site and it also regulates the osmotic pressure of blood. HSA is a carrier protein, abundantly (60%) present in human blood plasma contains 585 amino acids arranged as a single polypeptide chain. Among the amino acid residues, the region between 1–195, 196–383, and 384–585 resides as three major domains I, II, and III, respectively, namely Sudlow site I and II. Each domain comprises two sub-domains linked with 17 disulfide bridges with heart shape structure. When considering the binding region of HSA among the six subdomains, the principle binding region located at IIA and III A sub-domains due to the presence of Trp 214, Lys 199, Tyr 411 (Sudlow, Birkett, & Wade, 1975). Further, the major vital role of HSA is to transport and deliver the various drugs to multiple organs of the body with their good binding affinity and it also acts as receptor for fatty acid, bilirubin, warfarin, indole, benzodiazepines with the lowest binding affinity (Muller & Wollert, 1979). Most of the drugs were originated from the medicinal plants and it produced various classes of phyto-constituents including alkaloids, flavonoids, terpenoids, steroids and tannins as secondary metabolites were used as phyto-pharmaceutical drugs (Veeresham, 2012) with good binding properties on HSA. The different kinds of alkaloids and their binding affinity with HSA studied among scientific communities. In that, the piperine, Caffeine, indole, isomer of ciprofloxacin N, B, F, and I binds with HSA with binding constant of .5 × 10, 12 × 10, 4.2 × 10, 6.92 × 10, 3.87 × 10, 4.06 × 10, and 2.7 × 10 M, respectively. Likewise, various flavonoids also contain good binding properties with HSA such as quercetin, hyperin, baicalin, rutin, curcumin, and genistein. Similar binding studies were carried out in our laboratory with HSA along with different phytochemicals. For the last recent period our lab group reported the high binding affinity of HSA with different phytochemicals including trans-feruloylmaslinic acid, β – sitosterol, N-trans-p-coumaroyltyramine, betulinic acid, L-3,4 dihydroxy phenylalanine and piperine. Since 5-HMP has several important roles in curing many diseases but the understanding of bioavailability of the drug and its pharmacokinetics, HSA is a good model system. Moreover, the binding studies of 5-HMP are studied with plasma protein. Thus, the present study reveals the molecular interactions of such valuable phytochemical 5HMP with HSA by the formation of ligand–protein complexes as preliminary step of drug invention among the ADME feature (Benet, Kroetz, Sheiner, Hardman, & Limbird, 1996) and it is also an important factor that can
5-HMP, a piperidine alkaloid found in various medicinal plants, effectively binds to human serum albumin, transporting drugs to various organs and playing a vital role in drug delivery.
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