title: Design, synthesis and in vitro antiplasmodial activity of some bisquinolines against chloroquine-resistant strain.
abstract: A series of novel bisquinoline compounds comprising N1-(7-chloroquinolin-4-yl) ethane-1,2-diamine and 7-chloro-N-(2-(piperazin-1-yl)ethyl)quinolin-4-amine connected with 7-chloro-4-aminoquinoline containing various amino acids is described. We have bio-evaluated the compounds against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum in vitro. Among the series, compounds 4 and 7 exhibited 1.8- and 10.6-fold superior activity as compared to chloroquine (CQ; IC50= 0.255 ± 0.049 μm) against the K1 strain with IC50values 0.137 ± 0.014 and 0.026 ± 0.007 μm, respectively. Furthermore, compound 7 also displayed promising activity against the 3D7 strain (IC50= 0.024 ± 0.003 μm) of P. falciparum when compared to CQ. All the compounds in the series displayed resistance factor between 0.57 and 4.71 as against 51 for CQ. These results suggest that bisquinolines can be explored for further development as new antimalarial agents active against chloroquine-resistant P. falciparum.
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Srinivasarao
authors.initials: S
authors.lastname: Kondaparla
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Kumkum
authors.initials: K
authors.lastname: Srivastava
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Puri
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Seturam B
authors.initials: SB
authors.lastname: Katti
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D015195:Drug Design; D004351:Drug Resistance / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D011804:Quinolines; D002738:Chloroquine
keywords: 
  Plasmodium falciparum
  ; 4-Aminoquinoline; antiplasmodial activity; chloroquine; chloroquine-resistant strain; chloroquine-sensitive strain