Synergistic antimalarial activity of ketones with rufigallol and vitamin C

• Published in: Parasitology 2005-10, Vol.131 (4), p.459-466
• Main Authors: MAHAJAN, S. S., KAMATH, V. R., GHATPANDE, S. S.
• Format: Article
• Language: English
• Subjects: Animals; Anthraquinones - pharmacology; Anthraquinones - therapeutic use; Antimalarials - pharmacology; Antimalarials - therapeutic use; Antioxidants - therapeutic use; Ascorbic Acid - pharmacology; Ascorbic Acid - therapeutic use; Benzophenones - therapeutic use; Biological and medical sciences; Derivatives; Drug Resistance; Drug Synergism; Drug Therapy, Combination; Fundamental and applied biological sciences. Psychology; General aspects; General aspects and techniques. Study of several systematic groups. Models; Humans; Invertebrates; Ketones; Ketones - pharmacology; Ketones - therapeutic use; Malaria; Malaria - drug therapy; Malaria, Falciparum - drug therapy; Mice; Parasites; Parasitic Sensitivity Tests; Plasmodium berghei; Plasmodium berghei - drug effects; Plasmodium berghei - growth & development; Plasmodium falciparum; rufigallol and vitamin C; Statistical analysis; Synergism; synergistic antimalarial activity; Tables; Treatment Outcome; Vector-borne diseases; Vitamin C
• ISSN: 0031-1820; 1469-8161
• DOI: 10.1017/S0031182005008267

Malaria remains a major cause of human morbidity and mortality worldwide. Plasmodium falciparum, the most virulent of the 4 human Plasmodium species causing malaria, is potentially life threatening, is increasing in prevalence and is becoming even more resistant to in-use drugs. In light of the growing problem of multi-drug resistance to malarial parasites, the development of new drugs or the use of a combination therapy is of primary importance. A previous report describes a remarkable synergistic antimalarial interaction between 2 structurally similar compounds, rufigallol, an anthraquinone derivative and exifone, a benzophenone derivative, in vitro. The synergistic antimalarial activity of exifone and vitamin C was also reported. To extend the same analogy to other ketones, we carried out antimalarial testing of 20 benzophenone derivatives, individually, in combination with rufigallol, and also in combination with vitamin C, in mice infected with Plasmodium berghei. Five ketones, out of 20, showed good antimalarial activity, in vivo, when tested individually. Nine ketones, out of 20, showed good antimalarial activity, in vivo, when tested in combination with rufigallol, indicating the synergism between them. However, synergism between ketones and vitamin C was not satisfactory since only 2 ketones showed good antimalarial activity when tested in combination with vitamin C.