title: Synthesis and biological evaluation of 2,3-dihydroimidazo[1,2-a]benzimidazole derivatives against Leishmania donovani and Trypanosoma cruzi.
abstract: A high-throughput (HTS) and high-content screening (HCS) campaign of a commercial library identified 2,3-dihydroimidazo[1,2-a]benzimidazole analogues as a novel class of anti-parasitic agents. A series of synthetic derivatives were evaluated for their in vitro anti-leishmanial and anti-trypanosomal activities against Leishmania donovani and Trypanosoma cruzi, which have been known as the causative parasites for visceral leishmaniasis and Chagas disease, respectively. In the case of Leishmania, the compounds were tested in both intracellular amastigote and extracellular promastigote assays. Compounds 4 and 24 showed promising anti-leishmanial activity against intracellular L. donovani (3.05 and 5.29 μM, respectively) and anti-trypanosomal activity against T. cruzi (1.10 and 2.10 μM, respectively) without serious cytotoxicity toward THP-1 and U2OS cell lines.
authors.affiliation: Medicinal Chemistry Group, Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, South Korea.
authors.forename: Sangmi
authors.initials: S
authors.lastname: Oh
authors.affiliation: Medicinal Chemistry Group, Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, South Korea.
authors.forename: Sungbum
authors.initials: S
authors.lastname: Kim
authors.affiliation: Medicinal Chemistry Group, Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, South Korea.
authors.forename: Sunju
authors.initials: S
authors.lastname: Kong
authors.affiliation: Center for Neglected Diseases Drug Discovery (CND3), Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, South Korea.
authors.forename: Gyongseon
authors.initials: G
authors.lastname: Yang
authors.affiliation: Center for Neglected Diseases Drug Discovery (CND3), Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, South Korea.
authors.forename: Nakyung
authors.initials: N
authors.lastname: Lee
authors.affiliation: Center for Neglected Diseases Drug Discovery (CND3), Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, South Korea.
authors.forename: Dawoon
authors.initials: D
authors.lastname: Han
authors.affiliation: Center for Neglected Diseases Drug Discovery (CND3), Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, South Korea.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Goo
authors.affiliation: Center for Neglected Diseases Drug Discovery (CND3), Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, South Korea.
authors.forename: Jair L
authors.initials: JL
authors.lastname: Siqueira-Neto
authors.affiliation: Center for Neglected Diseases Drug Discovery (CND3), Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, South Korea.
authors.forename: Lucio H
authors.initials: LH
authors.lastname: Freitas-Junior
authors.affiliation: Medicinal Chemistry Group, Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, South Korea. Electronic address: rsong@ip-korea.org.
authors.forename: Rita
authors.initials: R
authors.lastname: Song
mesh_terms: D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: C000596761:9-(4-phenylbenzyl)-2,3-dihydroimidazo(1,2-a)benzimidazole; D000977:Antiparasitic Agents; D001562:Benzimidazoles; D006575:Heterocyclic Compounds, 3-Ring
keywords: 2,3-Dihydroimidazo[1,2-a]benzimidazole; Anti-parasitic activity; Chagas disease; Leishmaniasis