title: Design, synthesis and cytotoxicity of novel chalcone analogs derived from 1-cyclohexylpyrrolidin-2-one and 2,3-dihydrobenzo[f]chromen-1-one.
abstract: Two divergent series of novel chalcone analogs, one derived from 1-cyclohexylpyrrolidin-2-one and the other derived from 1-benzo[f]chromanone, were designed, synthesized and evaluated for cytotoxicity against two murine cancer cell lines. Two 1-benzo[f]chromanone analogs, 4g and 4j yielded moderate toxicity against both melanoma B16 and lymphoma L1210 cell lines with IC(50)  values between the range of 5 and 6 µM. With an IC(50)  value of 3.4 µM, compound 4g was also active against human MDA-MB-435 melanoma cells. X-ray structures of the β-hydroxy ketone product (4a) and the α,β-unsaturated ketone (4h) were collected, and confirm the syn-configuration between the carbonyl moiety and the β-vinylic proton in 4h. X-ray structures of two 1-cyclohexylpyrrolidin-2-one derivatives were also obtained, and both showed an E-configuration for the double bond.
authors.affiliation: Division of Natural Sciences and Department of Chemistry, Hope College, Holland, MI, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Brien
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Bandi
authors.forename: Ajaya Kumar
authors.initials: AK
authors.lastname: Behera
authors.forename: Bijay Kumar
authors.initials: BK
authors.lastname: Mishra
authors.forename: Poulomi
authors.initials: P
authors.lastname: Majumdar
authors.forename: Vijay
authors.initials: V
authors.lastname: Satam
authors.forename: Mia
authors.initials: M
authors.lastname: Savagian
authors.forename: Samuel
authors.initials: S
authors.lastname: Tzou
authors.forename: Megan
authors.initials: M
authors.lastname: Lee
authors.forename: Matthias
authors.initials: M
authors.lastname: Zeller
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Robles
authors.forename: Susan
authors.initials: S
authors.lastname: Mooberry
authors.forename: Hari
authors.initials: H
authors.lastname: Pati
authors.forename: Moses
authors.initials: M
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002867:Chromones / Q000737:chemistry*; D003510:Cyclohexanes / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D051379:Mice; D011760:Pyrrolidinones / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: C575206:1-cyclohexylpyrrolidin-2-one; C575207:2,3-dihydrobenzo(f)chromen-1-one; D000970:Antineoplastic Agents; D047188:Chalcones; D002867:Chromones; D003510:Cyclohexanes; D011760:Pyrrolidinones