title: A new bisbenzylisoquinoline alkaloid isolated from Thalictrum foliolosum, as a potent inhibitor of DNA topoisomerase IB of Leishmania donovani.
abstract: Chemical investigation of the stem of Thalictrum foliolosum resulted in the isolation of two new bisbenzylisoquinoline alkaloids (1 and 2) along with known protoberberine group of isoquinoline alkaloids thalifendine (3) and berberine (4). The structures of the new compounds were established by detailed 2D NMR spectral analysis with their configurations determined from their optical rotation values and confirmed using circular dichroism. Inhibitory activities of these four compounds against DNA topoisomerase IB of Leishmania donovani were evaluated. Compound 2 exhibited almost complete inhibition of the enzyme activity at 50 μM concentration and it was found to be effective in killing both wild type as well as SAG resistant promastigotes of the parasite.
authors.affiliation: Chemistry Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata - 700032, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Molecular Parasitology Laboratory, Infectious Diseases & Immunology Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata - 700032, India.
authors.forename: Somenath Roy
authors.initials: SR
authors.lastname: Chowdhury
authors.affiliation: Chemistry Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata - 700032, India.
authors.forename: Tapas
authors.initials: T
authors.lastname: Sarkar
authors.affiliation: Chemistry Division, Sir Padampat Singhania University, Udaipur, Rajasthan, India.
authors.forename: Tulika
authors.initials: T
authors.lastname: Chakrabarti
authors.affiliation: Molecular Parasitology Laboratory, Infectious Diseases & Immunology Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata - 700032, India.
authors.forename: Hemanta K
authors.initials: HK
authors.lastname: Majumder
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata - 700032, India.
authors.forename: Tarun
authors.initials: T
authors.lastname: Jha
authors.affiliation: Chemistry Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata - 700032, India. Electronic address: sbm.chem@gmail.com.
authors.forename: Sibabrata
authors.initials: S
authors.lastname: Mukhopadhyay
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000302:isolation & purification; D001599:Berberine / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification; D001600:Berberine Alkaloids / Q000737:chemistry / Q000302:isolation & purification; D002478:Cells, Cultured; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification; D007893:Leishmania donovani / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D031949:Thalictrum / Q000737:chemistry*; D059004:Topoisomerase I Inhibitors / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D000470:Alkaloids; D000981:Antiprotozoal Agents; D001600:Berberine Alkaloids; D007546:Isoquinolines; D059004:Topoisomerase I Inhibitors; D001599:Berberine; C477156:thalifendine; C009090:protoberberine; D004264:DNA Topoisomerases, Type I; C039109:isoquinoline
keywords: Bisbenzylisoquinoline alkaloid; DNA topoisomerase; Leishmania donovani; Thalictrum foliolosum