Synthesis and in vitro cytotoxicity evaluation of 4-aminoquinoline derivatives.
ABSTRACT A series of 4-aminoquinoline derivatives were synthesized by the reaction of 4-chloro-7-substituted-quinolines with the corresponding mono/dialkyl amines. The structures of the synthesized compounds were confirmed by NMR and FAB-MS spectral and elemental analyses. Subsequently, the compounds were examined for their cytotoxic effects on two different human breast tumor cell lines: MCF7 and MDA-MB468. Although all compounds examined were quite effective on both cell lines, the compound N'-(7-chloro-quinolin-4-yl)-N,N-dimethyl-ethane-1,2-diamine emerged as the most active compound of the series. It was particularly potent against MDA-MB 468 cells when compared to chloroquine and amodiaquine. The compound butyl-(7-fluoro-quinolin-4-yl)-amine showed more potent effects on MCF-7 cells when compared to chloroquine. Therefore, 4-aminoquinoline can serve as the prototype molecule for further development of a new class of anticancer agents.
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ABSTRACT: In the title compound, C(20)H(25)ClN(6) (2+)·2ClO(4) (-), the organic cation is roughly planar, as shown by the dihedral angle of 3.78 (3)° between the quinazoline and chloro-phenyl rings. The quinazoline ring is itself approximately planar, with an average deviation of 0.018 (4) Å. The organic cation adopts an E configuration with respect to the C= N double bond of the hyrazinyl group. The (dimethyl-aza-nium-yl)propyl-amino side chain is disordered over two sets of sites with occupancies of 0.768 (10) and 0.232 (10). In the crystal, two cations and four anions are linked by strong N-H⋯O hydrogen bonds. Weak C-H⋯O hydrogen bonds exist among these aggregates.Acta Crystallographica Section E Structure Reports Online 05/2012; 68(Pt 5):o1557-8. · 0.35 Impact Factor
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ABSTRACT: Chloroquine (CQ) is a cost effective antimalarial drug with a relatively good safety profile (or therapeutic index). However, CQ is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ-resistant strains, also reported for P. vivax. Despite CQ resistance, novel drug candidates based on the structure of CQ continue to be considered, as in the present work. One CQ analog was synthesized as monoquinoline (MAQ) and compared with a previously synthesized bisquinoline (BAQ), both tested against P. falciparum in vitro and against P. berghei in mice, then evaluated in vitro for their cytotoxicity and ability to inhibit hemozoin formation. Their interactions with residues present in the NADH binding site of P falciparum lactate dehydrogenase were evaluated using docking analysis software. Both compounds were active in the nanomolar range evaluated through the HRPII and hypoxanthine tests. MAQ and BAQ derivatives were not toxic, and both compounds significantly inhibited hemozoin formation, in a dose-dependent manner. MAQ had a higher selectivity index than BAQ and both compounds were weak PfLDH inhibitors, a result previously reported also for CQ. Taken together, the two CQ analogues represent promising molecules which seem to act in a crucial point for the parasite, inhibiting hemozoin formation.PLoS ONE 01/2012; 7(5):e37259. · 3.73 Impact Factor
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ABSTRACT: In the title compound, C(22)H(27)ClN(6)O(2) (2+)·2ClO(4) (-), the mol-ecule adopts an E conformation about the C=N double bond. The quinazoline ring is approximately planar, with an r.m.s. deviation of 0.0432 Å, and forms a dihedral angle of 5.77 (4)° with the chloro-phenyl ring. The crystal packing features N-H⋯O hydrogen bonds.Acta Crystallographica Section E Structure Reports Online 06/2012; 68(Pt 6):o1819. · 0.35 Impact Factor