ABSTRACT
A series of 3-substituted-2-hydroxy-1,4-naphthoquinone derivatives with a variety of side chains were successfully synthesized by Mannich reaction of 2-hydroxy-1,4-naphthoquinone (lawsone) with selected amines and aldehydes. All substances (1-16) were evaluated for in-vitro antimalarial activity against strains of Plasmodium falciparum by microculture radioisotope technique. Bioassay data revealed that ten derivatives (1-8, 11 and 13) displayed significantly good activity with values of IC50 ranging from 0.77 to 4.05 µg/mL. The best biological profile (IC50 = 0.77 µg/mL) was observed in compound 1, possessing a n-butyl substituted aminomethyl group. Experimental results support the potential use of our active Mannich components as promising antimalarial agents in the fight against malaria infections and multidrug resistance problems.
Subject(s)
Antimalarials/chemical synthesis , Malaria/drug therapy , Naphthoquinones/chemical synthesis , Plasmodium falciparum/drug effects , Antimalarials/pharmacology , Drug Evaluation, Preclinical , Drug Resistance, Multiple , Humans , Naphthoquinones/pharmacology , Structure-Activity RelationshipABSTRACT
Eleven new secondary metabolites (1-11), together with two known flavanones (12 and 13) and five known bibenzyls (14-18), were isolated from the root extract of Bauhinia purpurea. New compounds include eight dihydrodibenzoxepins (1-8), a dihydrobenzofuran (9), a novel spirochromane-2,1'-hexenedione (10), and a new bibenzyl (11). Antimycobacterial, antimalarial, antifungal, cytotoxic, and anti-inflammatory activities of the isolated compounds are reported, and biosynthetic pathways of these compounds are also discussed.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Antimalarials/isolation & purification , Antimalarials/pharmacology , Bauhinia/chemistry , Benzoxepins/isolation & purification , Benzoxepins/pharmacology , Bibenzyls/isolation & purification , Bibenzyls/pharmacology , Flavanones/isolation & purification , Flavanones/pharmacology , Plants, Medicinal/chemistry , Spiro Compounds/isolation & purification , Spiro Compounds/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Anti-Inflammatory Agents/chemistry , Antifungal Agents/chemistry , Antimalarials/chemistry , Benzoxepins/chemistry , Bibenzyls/chemistry , Flavanones/chemistry , Microbial Sensitivity Tests , Molecular Structure , Plant Roots/chemistry , Spiro Compounds/chemistry , ThailandABSTRACT
Fourteen ferrocenyl aminohydroxynaphthoquinones, analogues of atovaquone, were synthesized from the hydroxynaphthoquinone core. These novel atovaquone derivatives were tested for their in vitro activity against two apicomplexan parasites of medical importance, Toxoplasma gondii and Plasmodium falciparum, including resistant strains to atovaquone (T. gondii) and chloroquine (P. falciparum). Three of these ferrocenic atovaquone derivatives composed of the hydroxynaphthoquinone core plus an amino-ferrocenic group and an aliphatic chain with 6-8 carbon atoms were found to be significantly active against T. gondii. Moreover, these novel compounds were also effective against the atovaquone-resistant strain of T. gondii (Ato(R)).