Rhodacyanine Dyes as Antimalarials. 1. Preliminary Evaluation of Their Activity and Toxicity

Abstract

The rhodacyanine dye MKT-077 (1), a potent antitumor agent, was found to possess strong in vitro activity against Plasmodium falciparum and a low cytotoxicity. Several new rhodacyanine dyes related to 1, containing a variety of linked heterocyclic moieties, were synthesized, and their antimalarial potencies were evaluated. The synthetic rhodacyanines were found to have EC(50) values against P. falciparum in vitro in the range of 4-300 nM. Several compounds in this series have remarkable selective toxicity profiles (>100).

Synthesis and Evaluation of β-Carbolinium Cations as New Antimalarial Agents Based on π-Delocalized Lipophilic Cation (DLC) Hypothesis

“…Replacement of methyl group as an R 5 substituent by an ethyl group resulted in a 10-fold increase in antiplasmodial potency for 6ab (versus 6aa), but a 2-fold decrease in activity was observed for 6ce (versus 6cc). b-Hydroxyethyl substituent for R 5 group also lead decrease in activity (6pa versus 6pb). It was observed that counter anion (X Ϫ ) affected antiplasmodial properties to some extent (runs 9,11,12).…”

“…After cooling to ambient temperature, the resulting precipitate was collected by filtration, which was subjected to ion exchange polymer (Amberlyte IRA-400) to give 6cj (53. 5 42) were supplied by the Japanese Cancer Research Resources Bank (JCRB). FM3A cells were maintained in suspension culture at 37°C in a 5% CO 2 atmosphere in plastic bottles containing ES medium (Nissui Pharmaceuticals, Tokyo, Japan) supplemented with 2% heat-inactivated fetal bovine serum (Gibco, NY, U.S.A.).…”

“…3) So that, development of new class of antiprotozoal including antimalarial agents are required and the efforts are steadily increasing in non-profit institutions. 4) Recently we have reported the rhodacyanines, having a pdelocalized lipophilic cationic (DLC) structure, exhibit in vitro strong antiplasmodial and antileishmanial activities against Plasmodium falciparum 5,6) and against Leishmania major, 7) respectively, with low cytotoxicity against mammalian cell. The conceptual term, DLC, was originally proposed by Chen in their anticancer research work.…”

π-Delocalized Lipophilic Cations as New Candidates for Antimalarial, Antitrypanosomal and Antileishmanial Agents: Synthesis, Evaluation of Antiprotozoal Potency, and Insight into Their Action Mechanisms

“…24) We expected that DLCs could provide a new class of chemotherapeutics for the treatment of malaria. [25][26][27][28][29] …”

“…In this paper, the rhodacyanines synthesized by our group were categorized into five classes in the following manner: [0, 0], [1,0], and [0, 0, 0] rhodacyanines (classes I to III, respectively), [25][26][27][28] and [0, 0] and [0, 0, 0] azarhodacyanines (classes IV, V, respectively). 29) Dyes in classes I, II, and IV were distinguished by the length of the methine linkage between the heterocyclic A-rings and the rhodanine B-rings.…”