title: A new structural class of S-adenosylhomocysteine hydrolase inhibitors.
abstract: Effective inhibitors of S-adenosylhomocysteine hydrolase hold promise towards becoming useful therapeutic agents. Since most efforts have focused on the development of nucleoside analog inhibitors, issues regarding bioavailability and selectivity have been major challenges. Considering the marine sponge metabolite ilimaquinone was found to be a competitive inhibitor of S-adenosylhomocysteine hydrolase, new opportunities for developing selective new inhibitors of this enzyme have become available. Based on the activities of various hybrid analogs, SAR studies, pharmacophore modeling, and computer docking studies have lead to a predictive understanding of ilimaquinone's S-adenosylhomocysteine hydrolase inhibitory activities. These studies have allowed for the design and preparation of simplified structural variants possessing new furanoside bioisosteres with 100-fold greater inhibitory activities than that of the natural product.
authors.affiliation: Merkert Chemistry Center, Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA.
authors.forename: Byung Gyu
authors.initials: BG
authors.lastname: Kim
authors.forename: Tae Gyu
authors.initials: TG
authors.lastname: Chun
authors.forename: Hee-Yoon
authors.initials: HY
authors.lastname: Lee
authors.forename: Marc L
authors.initials: ML
authors.lastname: Snapper
mesh_terms: D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011809:Quinones / Q000737:chemistry* / Q000494:pharmacology*; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D011809:Quinones; D012717:Sesquiterpenes; C467077:ilimaquinone; D012435:S-Adenosylhomocysteine; D043383:Adenosylhomocysteinase