title: Synthesis, antitumor activity, and structure-activity relationship study of trihydroxylated 2,4,6-triphenyl pyridines as potent and selective topoisomerase II inhibitors.
abstract: A series of eighteen trihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of each phenyl rings attached to the central pyridine. They were evaluated for topoisomerase I and II inhibitory activity, and cytotoxicity against several human cancer cell lines for the development of novel anticancer agents. Most of the compounds exhibited strong and selective topoisomerase II inhibitory activity compared to the positive control, etoposide, and also displayed significant cytotoxicity in low micromolar range. Trihydroxylated 2,4,6-triphenyl pyridines were more potent than mono- and di-hydroxylated 2,4,6-triphenyl pyridines, which have been previously studied in our research group. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for the most compounds. Molecular docking study shows qualitatively consistent with the results of biological assays.
authors: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors: Radha
authors: R
authors: Karki
authors: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Chanmi
authors: C
authors: Park
authors: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Kyu-Yeon
authors: KY
authors: Jun
authors: College of Pharmacy, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors: Jun-Goo
authors: JG
authors: Jee
authors: Department of Emergency Medical Technology, Daejeon University, Daejeon 300-716, Republic of Korea.
authors: Jun-Ho
authors: JH
authors: Lee
authors: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors: Pritam
authors: P
authors: Thapa
authors: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors: Tara Man
authors: TM
authors: Kadayat
authors: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: ykwon@ewha.ac.kr.
authors: Youngjoo
authors: Y
authors: Kwon
authors: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: eslee@ynu.ac.kr.
authors: Eung-Seok
authors: ES
authors: Lee
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D010636:Phenols; D011725:Pyridines; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II
keywords: Anticancer agents; Cytotoxicity; Docking study; Topo II inhibitory activity; Topoisomerase I; Topoisomerase II; Trihydroxylated 2,4,6-triphenyl pyridines