title: Synthesis, molecular modeling, and evaluation of nonphenolic indole analogs of mycophenolic acid.
abstract: Based on the promising activity of an indole-3-carboxamide derivative, a nonphenolic analog of mycophenolic acid (MPA), we report herein the synthesis of a compound containing two important features for the activity of MPA, the ring methoxy and methyl. The synthesis was accomplished using two strategies; a method dependent on stepwise building of the hexenoate side chain followed by the indolecarboxamide ring system, and a convergent route that depended on 1,3-sigmatropic rearrangement as a key step. Docking experiments on both Chinese Hamster and Human Type-II inosine monophosphate dehydrogenase (IMPDH) showed that this compound has potential binding interactions with the NAD site. The analogs showed no activity against MCF7-S, MCF7-R, or IGR-OV1 cancer cells.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, 14260 USA. melaraby@prdus.jnj.com
authors.forename: Moustafa E
authors.initials: ME
authors.lastname: El-Araby
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Bernacki
authors.forename: Gergely M
authors.initials: GM
authors.lastname: Makara
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Pera
authors.forename: Wayne K
authors.initials: WK
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D006224:Cricetinae; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D009243:NAD; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid