Fast atom bombardment mass spectral analysis of three new oxidative products of primaquine

FAB mass spectrum of 5,5-di-[6-methoxy-8-(4'-amino-1'butyl amino)] quinoline (Pl) was recorded in three different concentrations to establish the structure of new oxidative products of primaquine and also the effect of matrix on percentage relative abundance of molecular as well as fragment ions which were demonstrated first time. At three concentrations, three different behaviors of matrix, molecular and fragment ions were observed. At higher concentration (>1 nM) molecular ion behaved as a base peak, but due to side reaction with matrix certain extra peak were also obtained. Thus, the higher concentration was interesting to show the side reaction of analyte with m-nitro-benzyl alcohol (NBA) but not for molecular weight determination. At the lowest concentration (<0.6 nM) matrix ion behaved as a base peak in addition to molecular ion. Therefore, this region of concentration is useful for determining the molecular weight of the compound. However, the mass spectra of 0.6-1 nM concentrations were useful for structural elucidation as compared to mass spectra below 0.6 nM and above 1 nM. Thus, fast atom bombardment mass spectrum with NBA as a matrix was recorded in between 0.6 and 1 nM concentrations for the structural elucidation of new compounds. Molecular ions and fragment ions of 5,5-di-[6-methoxy-8-(4'-amino-1' butyl amino)] quinoline (PI), 6-methoxy-5,8-di-[4'amino-1'-methyl butyl amino] quinoline (PII), and 5,5-di-[7-hydroxy-6-methoxy-8(4'-amino-1'-methyl butyl amino)] quinoline (PIII) were identified. The fragment ions were obtained due to ring cleavages, Retero-Diels-Alder reaction (RDA), loss of side chain, proton transfer and substituted groups of the ring. On the basis of the fragmentation schemes and molecular ion peaks the structure of three new compounds PI, PII and PIII were proposed. In vitro studies showed that the compounds PI and PH had four times more gametocytocidal activity than primaquine but the compound 6-methoxy-5,8-di-[4-amino-1'-methyl butyl amino] quinoline (PII) was found to have good gametocytocidal activity against Plasmodium yoelli infected mice at 10 mg kg(-1) dose in vivo. Therefore, the spectra reported might serve as reference for the development of new molecules for the radical cure of relapsing malaria. (C) 2003 Elsevier B.V. All rights reserved.