Title:A Century of Thioxanthones: Through Synthesis and Biological Applications
VOLUME: 20 ISSUE: 19
Author(s):A.M. Paiva, M.M. Pinto and E. Sousa
Affiliation:Centro de Quimica Medicinal, Universidade do Porto (CEQUIMED-UP), Laboratorio de Quimica Organica e Farmaceutica, Departamento de Ciencias Quimicas, Faculdade de Farmacia, Universidade do Porto, Rua Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal.
Keywords:Antischistosomal, antitumor, lucanthone, P-glycoprotein, photoinitiators, synthesis, thioxanthone.
Abstract:The interest in the synthesis and applications of thioxanthones, dibenzo-gamma-thiopyrones, started in the beginning
of the 20th century. Thioxanthones are traditionally synthesized via benzophenone, diarylthioether or diarylthioester
intermediates. In recent years, more efficient and cleaner synthetic methodologies are being applied to obtain
thioxanthone derivatives, especially for photochemical applications. Considering biological activities, the first thioxanthone
introduced in therapy in 1945 was Miracil D, as an antischistosomal agent. Since then, the variety of studies of biological/
pharmacological activities of thioxanthones led to the discovery of new agents and to the disclosure of their
mechanisms of action. Moreover, the ability to sensitize cancer cells suggested new and promising applications in chemotherapy.
New antitumor derivatives are being developed by molecular modifications such as isosterism (aza-thioxanthones
and aminoethylthioxanthones) or hybridation (psorospermine and acronycin analogues). The last generation of antitumor
thioxanthones rendered a derivative, SR271425, with an excellent preclinical antitumor efficacy. The last decade has been
excited in the research of thioxanthones with important achievements in both synthesis and biochemical applications, especially
in order to dissociate the antitumor activity from the toxicity of drug candidates. Recently, thioxanthones emerged
as dual inhibitors of P-glycoprotein and tumor cell growth. It is expected that in the following years new analogues with
the thioxanthone scaffold emerge in the field of anticancer therapy, with enhanced antitumor activity and without serious
side effects.
