title: Synthesis and antiangiogenic activity of 6-amido-2,4,5-trimethylpyridin-3-ols.
abstract: We recently reported that 6-aminoalkyl-2,4,5-trimethylpyridin-3-ols, novel series of 6-aminopyridin-3-ol-based antioxidants, have high antiangiogenic activities. In pursuit of wider variety in the analogues, we here report the synthesis and antiangiogenic activities of 6-amidoalkyl-2,4,5-trimethylpyridin-3-ols, which would not be considered excellent antioxidants because of the poorer electron-donating effect of the C(6)-amido group than the corresponding C(6)-amino group. The selected 6-amido compounds showed up to several fold-higher antiangiogenic activities and up to an order of magnitude better antitumor activities in the chick embryo chorioallantoic membrane (CAM) assay than SU4312, a positive control. We also found that paracetamol, as a direct phenolic analogue of our simplest 6-amidopyridin-3-ol, showed a moderate level of antiangiogenic activity. We propose this study will offer a basis for a scaffold of novel angiogenesis inhibitors that can perturb angiogenesis-related pathologies.
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Hyunji
authors.initials: H
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Suhrid
authors.initials: S
authors.lastname: Banskota
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Dong-Guk
authors.initials: DG
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Jae-Hui
authors.initials: JH
authors.lastname: Been
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Republic of Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Jin
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Jaya
authors.initials: J
authors.lastname: Gautam
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Hyeonjin
authors.initials: H
authors.lastname: Jang
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Republic of Korea. Electronic address: tnam@hanyang.ac.kr.
authors.forename: Tae-gyu
authors.initials: TG
authors.lastname: Nam
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: jakim@yu.ac.kr.
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: jeongb@ynu.ac.kr.
authors.forename: Byeong-Seon
authors.initials: BS
authors.lastname: Jeong
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A
keywords: Amidopyridinol; Angiogenesis; Antiangiogenic; Antitumor; Chick chorioallantoic membrane assay