title: 4-Nitro styrylquinoline is an antimalarial inhibiting multiple stages of Plasmodium falciparum asexual life cycle.
abstract: Drugs against malaria are losing their effectiveness because of emerging drug resistance. This underscores the need for novel therapeutic options for malaria with mechanism of actions distinct from current antimalarials. To identify novel pharmacophores against malaria we have screened compounds containing structural features of natural products that are pharmacologically relevant. This screening has identified a 4-nitro styrylquinoline (SQ) compound with submicromolar antiplasmodial activity and excellent selectivity. SQ exhibits a cellular action distinct from current antimalarials, acting early on malaria parasite's intraerythrocytic life cycle including merozoite invasion. The compound is a fast-acting parasitocidal agent and also exhibits curative property in the rodent malaria model when administered orally. In this report, we describe the synthesis, preliminary structure-function analysis, and the parasite developmental stage specific action of the SQ scaffold.
authors.affiliation: Division of Molecular Microbiology, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA.
authors.forename: Bracken F
authors.initials: BF
authors.lastname: Roberts
authors.affiliation: Department of Chemistry, University of Central Florida, Orlando, FL, USA.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, University of Central Florida, Orlando, FL, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Cleaveleand
authors.affiliation: Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, South Korea.
authors.forename: Sukjun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, South Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Lee
authors.affiliation: Center Pasteur, Yaounde, Cameroon.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Ayong
authors.affiliation: Department of Chemistry, University of Central Florida, Orlando, FL, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Division of Molecular Microbiology, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA. Electronic address: dchak@ucf.edu.
authors.forename: Debopam
authors.initials: D
authors.lastname: Chakrabarti
mesh_terms: D000284:Administration, Oral; D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D055808:Drug Discovery; D004912:Erythrocytes / Q000469:parasitology; D008018:Life Cycle Stages / Q000187:drug effects; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D052940:Merozoites / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D051381:Rats; D013343:Styrenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D013343:Styrenes; C000624193:UCF 501
keywords: Antimalarials; Antiplasmodials; Invasion inhibitor; Natural-product-like compounds; Styrylquinoline