title: Novel Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins with Potent in Vitro and in Vivo Anticancer Activities.
abstract: Docking studies of tubulin-targeting C2-substituted 7-deazahypoxanthine analogues of marine alkaloid rigidins led to the design and synthesis of compounds containing linear C2-substituents. The C2-alkynyl analogue was found to have double- to single-digit nanomolar antiproliferative IC50 values and showed statistically significant tumor size reduction in a colon cancer mouse model at nontoxic concentrations. These results provide impetus and further guidance for the development of these rigidin analogues as anticancer agents.
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University , San Marcos, Texas 78666, United States.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Medellin
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus , Aurora, Colorado 80045, United States.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University , San Marcos, Texas 78666, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Scott
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University , San Marcos, Texas 78666, United States.
authors.forename: R Matthew
authors.initials: RM
authors.lastname: Hill
authors.affiliation: Departments of Chemistry and Biology, New Mexico Tech , Socorro, New Mexico 87801, United States.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Frail
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University , San Marcos, Texas 78666, United States.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Dasari
authors.affiliation: Department of Biology, New Mexico State University , Las Cruces, New Mexico 88003, United States.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ontiveros
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University , Stellenbosch, Western Cape, South Africa.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pelly
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University , Stellenbosch, Western Cape, South Africa.
authors.forename: Willem A L
authors.initials: WA
authors.lastname: van Otterlo
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University , San Marcos, Texas 78666, United States.|Materials Science, Engineering, and Commercialization Program, Texas State University , San Marcos, Texas 78666, United States.
authors.forename: Tania
authors.initials: T
authors.lastname: Betancourt
authors.affiliation: Department of Biology, New Mexico State University , Las Cruces, New Mexico 88003, United States.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Shuster
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, National Cancer Institute, Frederick National Laboratory of Cancer Research, National Institutes of Health, Frederick, Maryland 21702, United States.
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, National Cancer Institute, Frederick National Laboratory of Cancer Research, National Institutes of Health, Frederick, Maryland 21702, United States.
authors.forename: Ruoli
authors.initials: R
authors.lastname: Bai
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus , Aurora, Colorado 80045, United States.
authors.forename: Daniel V
authors.initials: DV
authors.lastname: LaBarbera
authors.affiliation: Departments of Chemistry and Biology, New Mexico Tech , Socorro, New Mexico 87801, United States.
authors.forename: Snezna
authors.initials: S
authors.lastname: Rogelj
authors.affiliation: Departments of Chemistry and Biology, New Mexico Tech , Socorro, New Mexico 87801, United States.
authors.forename: Liliya V
authors.initials: LV
authors.lastname: Frolova
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University , San Marcos, Texas 78666, United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kornienko
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008387:Marine Toxins / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology; D014970:Xanthines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D008387:Marine Toxins; D014404:Tubulin; D050257:Tubulin Modulators; D014970:Xanthines; D003078:Colchicine