Novel metal chelating molecules with anticancer activity. Striking effect of the imidazole substitution of the histidine-pyridine-histidine system

Taha F S Ali; Kana Iwamaru; Halil Ibrahim Ciftci; Ryoko Koga; Masahiro Matsumoto; Yasunori Oba; Hiromasa Kurosaki; Mikako Fujita; Yoshinari Okamoto; Kazuo Umezawa; Mitsuyoshi Nakao; Takuichiro Hide; Keishi Makino; Jun-ichi Kuratsu; Mohamed Abdel-Aziz; Gamal El-Din A A Abuo-Rahma; Eman A M Beshr; Masami Otsuka

doi:10.1016/j.bmc.2015.07.044

Novel metal chelating molecules with anticancer activity. Striking effect of the imidazole substitution of the histidine-pyridine-histidine system

Bioorg Med Chem. 2015 Sep 1;23(17):5476-82. doi: 10.1016/j.bmc.2015.07.044. Epub 2015 Jul 29.

Authors

Taha F S Ali¹, Kana Iwamaru¹, Halil Ibrahim Ciftci¹, Ryoko Koga¹, Masahiro Matsumoto¹, Yasunori Oba¹, Hiromasa Kurosaki², Mikako Fujita³, Yoshinari Okamoto¹, Kazuo Umezawa⁴, Mitsuyoshi Nakao⁵, Takuichiro Hide⁶, Keishi Makino⁶, Jun-ichi Kuratsu⁶, Mohamed Abdel-Aziz⁷, Gamal El-Din A A Abuo-Rahma⁷, Eman A M Beshr⁸, Masami Otsuka⁹

Affiliations

¹ Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
² College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, Aichi 463-8521, Japan.
³ Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
⁴ Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
⁵ Department of Molecular Target Medicine Screening, School of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
⁶ Department of Neurosurgery, Faculty of Medicine, Kumamoto University, 1-1-1 Honjo Chuo-ku, Kumamoto 860-8556, Japan.
⁷ Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt.
⁸ 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.
⁹ 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.

PMID: 26260338
DOI: 10.1016/j.bmc.2015.07.044

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.

Keywords: AsPC-1; DNA cleavage; Histidine–pyridine–histidine; U251; U87.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chelating Agents / chemistry
DNA / chemistry*
Histidine / chemistry*
Humans
Imidazoles / chemistry*
Pyridines / chemistry*

Substances

Chelating Agents
Imidazoles
Pyridines
Histidine
imidazole
DNA
pyridine