Identification of a new class of low molecular weight antagonists against the chemokine receptor CXCR4 having the dipicolylamine-zinc(II) complex structure.
Several low molecular weight nonpeptide compounds having the dipicolylamine-zinc(II) complex structure were identified as potent and selective antagonists of the chemokine receptor CXCR4. These compounds showed strong inhibitory activity against CXCL12 binding to CXCR4, and the top compound exhibited significant anti-HIV activity. Zinc(II)-dipicolylamine unit-containing compounds proved to be useful and attractive lead compounds for chemotherapy of these diseases as nonpeptide CXCR4 antagonists possessing the novel scaffold structure.
Tamamura
Hirokazu
H
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan. tamamura.mr@tmd.ac.jp
Ojida
Akio
A
Ogawa
Teppei
T
Tsutsumi
Hiroshi
H
Masuno
Hiroyuki
H
Nakashima
Hideki
H
Yamamoto
Naoki
N
Hamachi
Itaru
I
Fujii
Nobutaka
N
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D015497:HIV-1 / Q000187:drug effects; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010847:Picolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D015032:Zinc
D019380:Anti-HIV Agents; D002614:Chelating Agents; D009942:Organometallic Compounds; D010847:Picolines; D019718:Receptors, CXCR4; C509592:zinc(II) dipicolylamine; D015032:Zinc; D002118:Calcium