title: ABL kinase inhibitory and antiproliferative activity of novel picolinamide based benzothiazoles.
abstract: A series of novel picolinamide based benzothiazoles (17 final compounds), targeting both wild-type and the most resistant T315I mutant of Bcr-Abl kinase, has been designed and synthesized. Moreover, a selected array (8 compounds) was evaluated for its antiproliferative activity over a panel of 60 cancer cell lines. Compound 5l was the most potent derivative against both native and T315I mutant ABL with IC50 values of 18.2 and 39.9nM, respectively, and showed highly selective inhibitory activity (89.8%) towards the Bcr-Abl dependent leukemia cell (K-562) at 10μM concentration. Significance of C6-oxypicolinamide moiety and SAR study for the C2 aliphatic side chain of benzothiazole are discussed in detail.
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), Hwarangro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), Gajungro 217, Youseong-gu, Daejeon 305-350, Republic of Korea.
authors.forename: Ashraf Kareem
authors.initials: AK
authors.lastname: El-Damasy
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), Hwarangro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Biotechnology, Yonsei University 220, Seoul 120-749, Republic of Korea.
authors.forename: Nam-Chul
authors.initials: NC
authors.lastname: Cho
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), Hwarangro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Soon Bang
authors.initials: SB
authors.lastname: Kang
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), Hwarangro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), Gajungro 217, Youseong-gu, Daejeon 305-350, Republic of Korea.
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), Hwarangro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), Gajungro 217, Youseong-gu, Daejeon 305-350, Republic of Korea. Electronic address: gkeum@kist.re.kr.
authors.forename: Gyochang
authors.initials: G
authors.lastname: Keum
mesh_terms: D000577:Amides / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D016374:Oncogene Proteins v-abl / Q000037:antagonists & inhibitors*; D010848:Picolinic Acids / Q000737:chemistry*
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D016374:Oncogene Proteins v-abl; D010848:Picolinic Acids; C003142:picolinamide
keywords: ABL kinase; Antiproliferative; Benzothiazole; Chronic myelogenous leukemia; Picolinamide; T315I mutant