The following are the objectives of Core B at The Ohio State University (OSU): (1) Synthesize sufficient quantities of selected natural products for more extensive biological evaluation, (2) Explore structure-activity relationships (SAR) and optimize pharmacological properties of highly promising agents through systematic modification of the natural product scaffold. All new compounds synthesized in these studies will be submitted for the bioassays proposed in Projects 1 and 3 and Core A, (3) Support the structural assignment of isolated natural products through chemical synthesis and/or semi-synthetic derivatization, as necessary, (4) Develop sensitive, selective, accurate and precise assays to quantify lead compounds in in vitro and in vivo biological matrices, (5) Characterize solubility, stability and metabolic profiles of lead compounds in dosing formulations and in vitro cell and enzyme preparations to support optimal formulation and derivatization, as necessary, and (6) Produce pilot plasma concentration-time profiles and determine protein and blood cell binding in mice for early estimation of pharmacokinetic properties for select compounds prior to entry into hollow fiber assays.
The primary goal of Core B is to support the discovery, characterization and optimization of novel anticancer agents through the synthesis, structural modification, and evaluation of pharmacokinetic properties of lead compounds discovered in Projects 1-3 that demonstrate promising biological activity.
|Sica, Vincent P; Rees, Evan R; Raja, Huzefa A et al. (2017) In situ mass spectrometry monitoring of fungal cultures led to the identification of four peptaibols with a rare threonine residue. Phytochemistry 143:45-53|
|Henkin, Joshua M; Sydara, Kongmany; Xayvue, Mouachanh et al. (2017) Revisiting the linkage between ethnomedical use and development of new medicines: A novel plant collection strategy towards the discovery of anticancer agents. Journal of medicinal plant research 11:621-634|
|Paguigan, Noemi D; Al-Huniti, Mohammed H; Raja, Huzefa A et al. (2017) Chemoselective fluorination and chemoinformatic analysis of griseofulvin: Natural vs fluorinated fungal metabolites. Bioorg Med Chem 25:5238-5246|
|Wang, Jiang; Zhu, Xiaohua; Kolli, Shamala et al. (2017) Plasma pharmacokinetics and bioavailability of verticillin A following different routes of administration in mice using liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal 139:187-192|
|Chen, Wei-Lun; Ren, Yulin; Ren, Jinhong et al. (2017) (+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks. J Nat Prod 80:659-669|
|Paguigan, Noemi D; El-Elimat, Tamam; Kao, Diana et al. (2017) Enhanced dereplication of fungal cultures via use of mass defect filtering. J Antibiot (Tokyo) 70:553-561|
|Ren, Yulin; Chen, Wei-Lun; Lantvit, Daniel D et al. (2017) Cardiac Glycoside Constituents of Streblus asper with Potential Antineoplastic Activity. J Nat Prod 80:648-658|
|Acuña, Ulyana Munoz; Curley Jr, Robert W; Fatima, Nighat et al. (2017) Differential Effect of Wortmannolone Derivatives on MDA-MB-231 Breast Cancer Cells. Anticancer Res 37:1617-1623|
|Ren, Yulin; Gallucci, Judith C; Kinghorn, A Douglas (2017) An Intramolecular CAr-H•••O=C Hydrogen Bond and the Configuration of Rotenoids. Planta Med 83:1194-1199|
|Brooks, Wilson C; Paguigan, Noemi D; Raja, Huzefa A et al. (2017) qNMR for profiling the production of fungal secondary metabolites. Magn Reson Chem 55:670-676|
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