title: In-vitro anti-proliferative and anti-oxidant activity of galangin, fisetin and quercetin: role of localization and intermolecular interaction in model membrane.
abstract: Flavonols are an important class of naturally occurring molecules and are known for their pharmacological activity. The activity is associated with the ability of flavonols to influence membrane-dependent processes. We have investigated the in-vitro anti-proliferative and anti-oxidant activity of galangin (GLN), fisetin (FTN) and quercetin (QTN), which possess variable number of phenolic hydroxyl groups. An attempt has been made to correlate the biological activity of these molecules with their interaction and localization in dipalmitoyl phosphatidyl choline (DPPC) bilayers, using differential dcanning calorimetry (DSC) and nuclear magnetic resonance (NMR) methods. Results indicate that GLN interacts to the alkyl chains of the lipid bilayer involving hydrophobic interactions. FTN and QTN interact with head region and sn-1-glycero region involving hydrogen bonding. Ring current induced chemical shifts of lipid protons, due to intermolecular interaction indicate that GLN acquires a parallel orientation with respect to the bilayer normal whereas FTN and QTN resume a mixed orientation. The membrane binding constants of these molecules are in the order GLN > QTN > FTN. It has been shown that the number and position of hydroxyl groups in these molecules play an important role in membrane binding and thereby in biological activity.
authors.affiliation: National Facility for High Field NMR, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
authors.forename: Ragini
authors.initials: R
authors.lastname: Sinha
authors.affiliation: National Facility for High Field NMR, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India. Electronic address: sudha@tifr.res.in.
authors.forename: Sudha
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Principal K M Kundnani College of Pharmacy, Cuffe Parade, Mumbai 400005, India.
authors.forename: Akshada
authors.initials: A
authors.lastname: Joshi
authors.affiliation: Principal K M Kundnani College of Pharmacy, Cuffe Parade, Mumbai 400005, India.
authors.forename: Urmila J
authors.initials: UJ
authors.lastname: Joshi
authors.affiliation: National Facility for High Field NMR, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
authors.forename: Girjesh
authors.initials: G
authors.lastname: Govil
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D044948:Flavonols; D056945:Hep G2 Cells; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D008567:Membranes, Artificial; D008958:Models, Molecular; D015394:Molecular Structure; D011794:Quercetin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D005419:Flavonoids; D044948:Flavonols; D008567:Membranes, Artificial; C037032:galangin; D011794:Quercetin; C017875:fisetin
keywords: Chemical shift anisotropy; Differential scanning calorimetry; Dipalmitoyl phosphatidyl choline; Flavonols; Nuclear magnetic resonance; Ring current shifts