title: Design and synthesis of new imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrazine derivatives with antiproliferative activity against melanoma cells.
abstract: Melanoma is an aggressive form of skin cancer and it is generally associated with poor prognosis in patients with late-stage disease. Due to the increasing occurrence of melanoma, there is a need for the development of novel therapies. A new series of diarylamide and diarylurea derivatives containing imidazo[1,2-a]pyridine or imidazo[1,2-a]pyrazine scaffold was designed and synthesized to investigate their in vitro efficacy against the A375P human melanoma cell line. We found several compounds expressing submicromolar IC50 values against the A375P cells, from which 15d, 17e, 18c, 18h, 18i demonstrated the highest potencies with IC50 below 0.06 μM.
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary; Vichem Chemie Research Ltd., Budapest, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Garamvölgyi
authors.affiliation: Vichem Chemie Research Ltd., Budapest, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Dobos
authors.affiliation: Vichem Chemie Research Ltd., Budapest, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Sipos
authors.affiliation: Vichem Chemie Research Ltd., Budapest, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Boros
authors.affiliation: Vichem Chemie Research Ltd., Budapest, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Illyés
authors.affiliation: Vichem Chemie Research Ltd., Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Baska
authors.affiliation: Vichem Chemie Research Ltd., Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Kékesi
authors.affiliation: Vichem Chemie Research Ltd., Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Szabadkai
authors.affiliation: Vichem Chemie Research Ltd., Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Szántai-Kis
authors.affiliation: Vichem Chemie Research Ltd., Budapest, Hungary; MTA-SE Pathobiochemistry Research Group, Department of Medical Chemistry, Semmelweis University, Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Kéri
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary; Vichem Chemie Research Ltd., Budapest, Hungary. Electronic address: orfi.laszlo@pharma.semmelweis-univ.hu.
authors.forename: László
authors.initials: L
authors.lastname: Őrfi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology*; D015394:Molecular Structure; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D011719:Pyrazines; D011725:Pyridines; C556838:imidazo(1,2-a)pyrazine; C001439:imidazo(1,2-a)pyridine
keywords: A375P; Antiproliferative activity; Diarylamide; Diarylurea; Imidazo[1,2-a]pyrazine; Imidazo[1,2-a]pyridine; Melanoma