ABSTRACT
A series of tetraoxanes, tetraoxane-amine and tetraoxane-amide conjugates have been synthesized and screened for in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Most of the conjugates showed slightly better antimalarial activity than the parent tetraoxanes. Three of the conjugate compounds were potentially active with IC(50) values in the range of 0.38-0.80µM. Cytotoxicity of four selected compounds was also evaluated in a panel of four cancer (SK-MEL, KB, BT-549, SK-OV-3) and two non-cancer (Vero and LLC-PK(11)) cell lines up to a concentration of 25µM and none of the compounds was found toxic to any of the cells.
Subject(s)
Antimalarials/chemical synthesis , Plasmodium falciparum/drug effects , Tetraoxanes/chemical synthesis , Amides/chemistry , Amines/chemistry , Animals , Antimalarials/pharmacology , Artemisinins/pharmacology , Cell Line, Tumor , Chlorocebus aethiops , Chloroquine/pharmacology , Dose-Response Relationship, Drug , Drug Design , Drug Resistance , Humans , Inhibitory Concentration 50 , Structure-Activity Relationship , Tetraoxanes/pharmacology , Vero CellsABSTRACT
A novel iodine-catalyzed one-pot synthesis of symmetrically and asymmetrically substituted 3,6-diphenyl-[1,2,4,5]tetraoxanes is described. The synthetic protocol is general with substituted benzaldehydes and proceeds well under acidic conditions. Total 17 tetraoxanes have been prepared during this study and some of these compounds exhibit promising antimalarial activity. None of the compounds shows any toxicity against vero cells.
Subject(s)
Antimalarials/chemical synthesis , Artemisinins/pharmacology , Iodine/pharmacology , Malaria, Falciparum/drug therapy , Plasmodium falciparum/metabolism , Tetraoxanes/chemical synthesis , Animals , Antimalarials/pharmacology , Chemistry, Organic/methods , Chemistry, Pharmaceutical/methods , Chlorocebus aethiops , Drug Design , Inhibitory Concentration 50 , Models, Chemical , Molecular Structure , Tetraoxanes/pharmacology , Vero CellsABSTRACT
Symmetrically and asymmetrically substituted 1,2,4,5-tetraoxanes were synthesized by the oxidative system H(2)O(2)/TFE in presence of MeReO(3) as a catalyst. All of the synthesized compounds were characterized spectroscopically, and evaluated for cytotoxicity, and antimalarial activity. Several of these tetraoxanes exhibited in vitro antimalarial activity without showing any cytotoxicity. Thermal stability of these compounds was studied by differential scanning calorimetry.
Subject(s)
Antimalarials/chemical synthesis , Antimalarials/pharmacology , Tetraoxanes/chemical synthesis , Tetraoxanes/pharmacology , Animals , Antimalarials/chemistry , Benzene Derivatives/chemical synthesis , Benzene Derivatives/chemistry , Benzene Derivatives/pharmacology , Calorimetry, Differential Scanning , Chloroquine/pharmacology , Drug Stability , Erythrocytes/parasitology , Hot Temperature , Humans , Inhibitory Concentration 50 , Malaria, Falciparum/blood , Malaria, Falciparum/drug therapy , Plasmodium falciparum , Structure-Activity Relationship , Tetraoxanes/chemistryABSTRACT
Advances in the sophisticated instruments for the isolation and characterization of marine natural products, and development in the biological assay systems, have resulted in the discovery of various compounds of biomedical application. Marine natural products have been a source of new leads for the treatment of many deadly diseases such as cancer, acquired immuno-deficiency syndrome (AIDS) etc. The compounds of marine origin are diverse in structural class from simple linear peptides to complex macrocyclic polyethers. Number of marine peptides have been isolated in recent years which exhibit potent biological activities, and many of the compounds showed promising anticancer activity. Didemnin was the first marine peptide that entered in human clinical trials in US for the treatment of cancer, and other anticancer peptides such as kahalalide F, hemiasterlin, dolastatins, cemadotin, soblidotin, didemnins and aplidine have entered in the clinical trials. Clinical status of anticancer marine derived peptides have been discussed and reviewed.
