title: Synthesis and anticancer activity of benzoselenophene and heteroaromatic derivatives of 1,2,9,9a-tetrahydrocyclopropa[c]benzo[e]indol-4-one (CBI).
abstract: The current study reports the synthesis of different derivatives of benzoselenophene analogs as well as a diverse series of compounds (14a-p, 15 and 16) from 1,2,9,9a-tetrahydrocyclopropa[c]benzo[e]indol-4-one (CBI) and benzoselenophene or heteroaromatic acids. The overall yield of scaffold 12 was improved by an one-pot reaction, which helps in large-scale synthesis of CBI, a duocarmycin alkylation subunit analog. The series of compounds were evaluated for their cytotoxicity against SK-OV3 ovarian cancer cell lines, which revealed that benzoselenophene can enhance or maintain the anticancer activity of the duocarmycin analog upon replacing the indole moiety. CBI-benzoselenophenes with N-amido substituents at the C-5 position, 14g, 14f and 16 (IC50= 0.5, 1.2 and 1.6 nM, respectively), were found to be more potent than the CBI-TMI and other benzoselenophene analogs. The CBI-benzoselenophene analogs, 14f and 14g (containing N-acetamido and N-butyramido substituents, respectively), were found to be 8 and 120 times more potent than the corresponding indole analogs of CBI, 14q and 14r, respectively.
authors.affiliation: Department of Chemistry, Sejong University, Seoul 143-747, Republic of Korea. dylim@sejong.ac.kr.
authors.forename: Amol B
authors.initials: AB
authors.lastname: Mhetre
authors.affiliation: Department of Chemistry, Sejong University, Seoul 143-747, Republic of Korea. dylim@sejong.ac.kr.
authors.forename: Hangeun
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Heekyoung
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kyoungmin
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
authors.affiliation: Department of Chemistry, Sejong University, Seoul 143-747, Republic of Korea. dylim@sejong.ac.kr.
authors.forename: Dongyeol
authors.initials: D
authors.lastname: Lim
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003521:Cyclopropanes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C506823:1,2,9,9a-tetrahydrocyclopropa(1,2-c)benz(1,2-e)indol-4-one; D000970:Antineoplastic Agents; D003521:Cyclopropanes; D006571:Heterocyclic Compounds; D006841:Hydrocarbons, Aromatic; D007211:Indoles; D016566:Organoselenium Compounds