title: Structure-activity relationships of retro-dihydrochalcones isolated from Tacca sp.
abstract: Several biologically active compounds have been identified from Tacca species, including glycosides, diarylheptanoids, saponins, withanolides, and the taccalonolide class of microtubule stabilizers. More recently, two cytotoxic retro-dihydrochalcones named evelynin A (7) and taccabulin A (6) were isolated and their biological activities characterized, including the finding that taccabulin has microtubule destabilizing effects. Here we describe the identification and characterization of five new retro-chalcones, named taccabulins B-E (1-4) and evelynin B (5) from Tacca sp. extracts. Their structures were determined using 1D and 2D NMR as well as mass spectroscopic data and modeled into the colchicine binding site of tubulin. The antiproliferative and microtubule effects of each compound were determined experimentally and found to be well correlated with modeling studies. The isolation and biological characterization of several retro-dihydrochalcones facilitated preliminary structure-activity relationships for this compound class concerning its antiproliferative and microtubule depolymerizing activities.
authors.affiliation: Department of Pharmacology, ‡Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229, United States.
authors.forename: Jiangnan
authors.initials: J
authors.lastname: Peng
authors.forename: April L
authors.initials: AL
authors.lastname: Risinger
authors.forename: Chenxiao
authors.initials: C
authors.lastname: Da
authors.forename: Gary A
authors.initials: GA
authors.lastname: Fest
authors.forename: Glen E
authors.initials: GE
authors.lastname: Kellogg
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mooberry
mesh_terms: D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology; D047188:Chalcones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D027743:Dioscoreaceae / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013329:Structure-Activity Relationship
chemical_list: D016227:Benzoquinones; D047188:Chalcones; D006027:Glycosides; C552992:evelynin