Chloroacridine derivatives as potential anticancer agents which may act as tricarboxylic acid cycle enzyme inhibitors.

Purpose: This paper concerns the cytotoxicity of 9-chloro-1-nitroacridine (1a) and 9-chloro-4-methyl-1-nitroacridine (1b) against two biologically different melanoma forms: melanotic and amelanotic. Melanomas are tumors characterized by high heterogeneity and poor susceptibility to chemotherapies. Among new analogs synthesized by us, compound 1b exhibited the highest anticancer potency.

Novel therapeutic compound acridine-retrotuftsin action on biological forms of melanoma and neuroblastoma.

Purpose: As a continuation of our search for anticancer agents, we have synthesized a new acridine-retrotuftsin analog HClx9-[Arg(NO)-Pro-Lys-Thr-OCH]-1-nitroacridine (named ART) and have evaluated its activity against melanoma and neuroblastoma lines. Both tumors develop from cells (melanocytes, neurons) of neuroectodermal origin, and both are tumors with high heterogeneity and unsatisfactory susceptibility to chemotherapies. Thus, we analyzed the action of ART on pairs of biological forms of melanoma (amelanotic and melanotic) and neuroblastoma (dopaminergic and cholinergic) with regard to proliferation, mechanism of cell death, and effect on the activity of tricarboxylic acid cycle (TAC) enzymes.

Synthesis and Biological Evaluation of Acridine/Acridone Analogs as Potential Anticancer Agents.

Background: The lack of efficacious therapy for advanced melanoma and neuroblastoma makes new approaches necessary. Therefore, many scientists seek new, more effective, more selective and less toxic anticancer drugs.

Objective: We propose the synthesis of the new functionalized analogs of 1-nitroacridine/4- nitroacridone connected to tuftsin/retro-tuftsin derivatives as potential anticancer agents.

Tuftsin - Properties and Analogs.

Background: Immunomodulation is one of the significant therapeutic strategies. It includes both stimulation and suppression of the immune system by a variety of substances called immunomodulators, designed to regulate the immune response of the organism against infections of varying etiology. An example of such a substance is tuftsin (TKPA) 3 (Fig.