title: Synthesis of primaquine glyco-conjugates as potential tissue schizontocidal antimalarial agents.
abstract: Primaquine (PQ) is the only drug used to prevent relapse of malaria due to P. vivax and P. ovale, by eradicating the dormant liver form of the parasite (hypnozoites). The side-effects associated with PQ limits is uses in treatment of malaria. To overcome the premature oxidative deamination and to increase the life span of drug in the biological system, the novel glyco-conjugates of PQ were synthesized by coupling of primaquine with hexoses in phosphate buffer. The saccharide part of the hybrid molecules thought to direct the drug to the liver, where hypnozoites resides. All the synthesized compounds were fully characterized and evaluated for their radical curative activities. The three compounds viz glucoside (15a), galactoside (15b) and mannoside (15c) with high activity were tested for their activity in rhesus monkeys where the most active compound 15b showed twofold activity (100% radical curative activity at 1.92 mmol/kg) than the standard drug PQ diphosphate (3.861 mmol/kg). It is proposed that results from these studies may be advantageous to develop a new potent tissue schizonticide antimalarial compound.
authors.affiliation: Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow, UP, India.
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Azad
authors.affiliation: Department of Chemistry, Amity University (Lucknow Campus), Lucknow, UP, India.
authors.forename: Mridula
authors.initials: M
authors.lastname: Saxena
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, UP, India.
authors.forename: Arif J
authors.initials: AJ
authors.lastname: Siddiqui
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, UP, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Bhardwaj
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, UP, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Puri
authors.affiliation: Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow, UP, India.
authors.forename: Guru P
authors.initials: GP
authors.lastname: Dutta
authors.affiliation: Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow, UP, India.
authors.forename: Nitya
authors.initials: N
authors.lastname: Anand
authors.affiliation: Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow, UP, India.
authors.forename: Anil K
authors.identifier: 0000-0002-0212-7246
authors.initials: AK
authors.lastname: Saxena
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008253:Macaca mulatta; D008288:Malaria / Q000188:drug therapy*; D016780:Malaria, Vivax / Q000188:drug therapy; D008297:Male; D051379:Mice; D010961:Plasmodium / Q000187:drug effects*; D016789:Plasmodium cynomolgi / Q000187:drug effects; D010966:Plasmodium vivax / Q000187:drug effects; D011319:Primaquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D006001:Glycoconjugates; D011319:Primaquine
keywords: 8-amino quinolones; phosphate buffer; primaquine diphosphate; radical curative activity; tissue schizontocidal activity