title: Flavonoid dimers as novel, potent antileishmanial agents.
abstract: The present study found that synthetic flavonoid dimers with either polyethylene glycol linker or amino ethyleneglycol linker have marked leishmanicidal activity. Compound 39 showed very consistent and promising leishmanicidal activity for both extracellular promastigotes (IC₅₀ ranging from 0.13 to 0.21 μM) and intracellular amastigotes (IC₅₀ = 0.63 μM) irrespective of the drug-sensitivity of parasites. Moreover, compound 39 displayed no toxicity toward macrophage RAW 264.7 cells (IC₅₀ > 100 μM) and primary mouse peritoneal elicited macrophages (IC₅₀ > 88 μM). Its high value of therapeutic index (>140) was better than other highly potent antileishmanials such as amphotericin B (therapeutic index = 119). Compound 39 is therefore a new, safe, and effective antileishmanial candidate compound which is even effective against drug-refractory parasites.
authors.affiliation: Department of Applied Biology and Chemical Technology and the State Key Laboratory for Chirosciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.
authors.forename: Iris L K
authors.initials: IL
authors.lastname: Wong
authors.forename: Kin-Fai
authors.initials: KF
authors.lastname: Chan
authors.forename: Tak Hang
authors.initials: TH
authors.lastname: Chan
authors.forename: Larry M C
authors.initials: LM
authors.lastname: Chow
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D019281:Dimerization; D004351:Drug Resistance; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000981:Antiprotozoal Agents; D005419:Flavonoids; D011092:Polyethylene Glycols