title: Synthesis and evaluation of quinazolinone derivatives as inhibitors of NF-kappaB, AP-1 mediated transcription and eIF-4E mediated translational activation: inhibitors of multi-pathways involve in cancer.
abstract: In our effort to discover and develop small molecule multi-pathway inhibitors which may be useful as tools for treating cancerous conditions, we have synthesized a small library of 2-thiazole-5-yl-3H-quinazolin-4-one derivatives. Synthesized compounds were evaluated as inhibitors of NF-kappaB and AP-1 mediated transcriptional and eIF-4E mediated translational activation as these transcription and translation factors are known to play a pivotal role in initiation and progression of cancer. The results from the study suggest the utility of the 2-thiazole-5-yl-3H-quinazolin-4-one scaffold as a promising scaffold for the design of novel multi-pathway inhibitors, which can be explored as anti-cancer agents.
authors.affiliation: B. V. Patel Pharmaceutical Education and Research Development Centre, S.G. Road, Thaltej, Ahmedabad 54, India.
authors.forename: Rajan S
authors.initials: RS
authors.lastname: Giri
authors.forename: Hardik M
authors.initials: HM
authors.lastname: Thaker
authors.forename: Tony
authors.initials: T
authors.lastname: Giordano
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Sam
authors.initials: S
authors.lastname: Nuthalapaty
authors.forename: Kamala K
authors.initials: KK
authors.lastname: Vasu
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Sudarsanam
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects*; D011487:Protein Conformation; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D039561:Eukaryotic Initiation Factor-4E; D016328:NF-kappa B; D052999:Quinazolinones; D018808:Transcription Factor AP-1