title: Synthesis, antiprotozoal, antimicrobial, β-hematin inhibition, cytotoxicity and methemoglobin (MetHb) formation activities of bis(8-aminoquinolines).
abstract: In continuing our search of potent antimalarials based on 8-aminoquinoline structural framework, three series of novel bis(8-aminoquinolines) using convenient one to four steps synthetic procedures were synthesized. The bisquinolines were evaluated for in vitro antimalarial (Plasmodiumfalciparum), antileishmanial (Leishmaniadonovani), antimicrobial (a panel of pathogenic bacteria and fungi), cytotoxicity, β-hematin inhibitory and methemoglobin (MetHb) formation activities. Several compounds exhibited superior antimalarial activities compared to parent drug primaquine. Selected compounds (44, 61 and 79) when tested for in vivo blood-schizontocidal antimalarial activity (Plasmodiumberghei) displayed potent blood-schizontocial activities. The bisquinolines showed negligible MetHb formation (0.2-1.2%) underlining their potential in the treatment of glucose-6-phosphate dehydrogenase deficient patients. The bisquinoline analogues (36, 73 and 79) also exhibited promising in vitro antileishmanial activity, and antimicrobial activities (43, 44 and 76) against a panel of pathogenic bacteria and fungi. The results of this study provide evidence that bis(8-aminoquinolines), like their bis(4-aminoquinolines) and artemisinin dimers counterparts, are a promising class of antimalarial agents.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India.
authors.forename: Kirandeep
authors.initials: K
authors.lastname: Kaur
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Jain
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Jacob
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.forename: Savita
authors.initials: S
authors.lastname: Singh
authors.forename: Prati Pal
authors.initials: PP
authors.lastname: Singh
authors.forename: Rahul
authors.initials: R
authors.lastname: Jain
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D006420:Hemeproteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008706:Methemoglobin / Q000096:biosynthesis*
chemical_list: D000634:Aminoquinolines; D000890:Anti-Infective Agents; D000981:Antiprotozoal Agents; D006420:Hemeproteins; C020753:hemozoin; D008706:Methemoglobin