title: Novel metal chelating molecules with anticancer activity. Striking effect of the imidazole substitution of the histidine-pyridine-histidine system.
abstract: Previously we have reported a metal chelating histidine-pyridine-histidine system possessing a trityl group on the histidine imidazole, namely HPH-2Trt, which induces apoptosis in human pancreatic adenocarcinoma AsPC-1 cells. Herein the influence of the imidazole substitution of HPH-2Trt was examined. Five related compounds, HPH-1Trt, HPH-2Bzl, HPH-1Bzl, HPH-2Me, and HPH-1Me were newly synthesized and screened for their activity against AsPC-1 and brain tumor cells U87 and U251. HPH-1Trt and HPH-2Trt were highly active among the tested HPH compounds. In vitro DNA cleavage assay showed both HPH-1Trt and HPH-2Trt completely disintegrate pUC19 DNA. The introduction of trityl group decisively potentiated the activity.
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Taha F S
authors.initials: TF
authors.lastname: Ali
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Iwamaru
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Halil Ibrahim
authors.initials: HI
authors.lastname: Ciftci
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Koga
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Oba
authors.affiliation: College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, Aichi 463-8521, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Kurosaki
authors.affiliation: Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Mikako
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.affiliation: Department of Molecular Target Medicine Screening, School of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Nakao
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Kumamoto University, 1-1-1 Honjo Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Takuichiro
authors.initials: T
authors.lastname: Hide
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Kumamoto University, 1-1-1 Honjo Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Makino
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Kumamoto University, 1-1-1 Honjo Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kuratsu
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt.
authors.forename: Gamal El-Din A A
authors.initials: Gel-D
authors.lastname: Abuo-Rahma
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt; Department of pharmaceutical Chemistry, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
authors.forename: Eman A M
authors.initials: EA
authors.lastname: Beshr
authors.affiliation: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. Electronic address: motsuka@gpo.kumamoto-u.ac.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Otsuka
mesh_terms: D002614:Chelating Agents / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*
chemical_list: D002614:Chelating Agents; D007093:Imidazoles; D011725:Pyridines; D006639:Histidine; C029899:imidazole; D004247:DNA; C023666:pyridine
keywords: AsPC-1; DNA cleavage; Histidine–pyridine–histidine; U251; U87