title: Synthesis of novel tadalafil analogues and their evaluation as phosphodiesterase inhibitors and anticancer agents.
abstract: Two closely related series of novel beta-carboline derivatives, electronically similar to tadalafil (CAS 171596-29-5), were synthesized and evaluated for their inhibitory effects upon phosphodiesterase 5 (PDE5) and phosphodiesterase 11 (PDE11) and their in vitro tumor cell growth inhibitory activity versus HT29 colorectal carcinoma cell line. Interestingly, some of the synthesized compounds showed growth inhibitory properties that appear to be associated with their ability to inhibit PDE5. Moreover, the PDE5 inhibition seems relevant to the stereochemical aspects of the compounds.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt. ashraf.abadi@guc.edu.eg
authors.forename: Ashraf H
authors.initials: AH
authors.lastname: Abadi
authors.forename: Dalal A
authors.initials: DA
authors.lastname: Abouel-Ella
authors.forename: Nermin S
authors.initials: NS
authors.lastname: Ahmed
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Gary
authors.forename: Jose T
authors.initials: JT
authors.lastname: Thaiparambil
authors.forename: Heather N
authors.initials: HN
authors.lastname: Tinsley
authors.forename: Adam B
authors.initials: AB
authors.lastname: Keeton
authors.forename: Gary A
authors.initials: GA
authors.lastname: Piazza
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002855:Chromatography, Thin Layer; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D000068581:Tadalafil
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D000068581:Tadalafil