Design and Synthesis of Pironetin Analogue/Combretastatin A-4 Hybrids and Evaluation of Their Cytotoxic Activity

• Published in: European journal of organic chemistry Vol. 2014; no. 11; pp. 2284 - 2296
• Main Authors: Torijano-Gutiérrez, Sandra, Vilanova, Concepción, Díaz-Oltra, Santiago, Murga, Juan, Falomir, Eva, Carda, Miguel, Marco, J. Alberto
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.04.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Anticancer agents; Chemistry; Chemistry, Organic; Cytotoxicity; Drug design; Medicinal chemistry; Physical Sciences; Science & Technology; Structure-activity relationships; Medicinal chemistry; MICROTUBULE; NATURAL-PRODUCTS; EFFICIENT SYNTHESIS; Cytotoxicity; Anticancer agents; Structure-activity relationships; CANCER-THERAPY; BIOLOGICAL EVALUATION; Drug design; AGENTS; ENANTIOSELECTIVE TOTAL-SYNTHESIS; ASYMMETRIC TOTAL-SYNTHESIS; TUBULIN BINDING MODE
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201301725

We describe the preparation of a series of hybrid molecules containing a combretastatin A‐4 moiety and a pironetin analogue fragment linked by an ester spacer of variable length. The cytotoxic activities of these compounds have been measured and the relationship between the structure and cytotoxicity is discussed. Some of the tested compounds showed cytotoxicity values of the same order of magnitude as those of the parental molecules, combretastatin A‐4 and pironetin, and were less toxic than the latter for normal cells. The preparation of a series of hybrid molecules containing a combretastatin A‐4 moiety and a pironetin analogue fragment linked by a spacer of variable length is described. The relationship between structure and cytotoxicity is discussed. Cytotoxicity values of some compounds were similar to those of the parent molecules, combretastatin A‐4 and pironetin, and some were less toxic than the latter for normal cells.