Purine and Purine Isostere Derivatives of Ferrocene: An Evaluation of ADME, Antitumor and Electrochemical Properties

• Main Authors: Valentina Rep, Martina Piškor, Helena Šimek, Petra Mišetić, Petra Grbčić, Jasna Padovan, Vesna Gabelica Marković, Dijana Jadreško, Krešimir Pavelić, Sandra Kraljević Pavelić, Silvana Raić-Malić
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: Molecules
• Subjects: purine; ferrocene; cytostatic activity; permeability; microsomal stability
• Online Access: https://www.mdpi.com/1420-3049/25/7/1570
• ISSN: 1420-3049

Novel purine and purine isosteres containing a ferrocene motif and 4,1-disubstituted (<b>11a</b>−<b>11c</b>, <b>12a</b>−<b>12c</b>, <b>13a</b>−<b>13c</b>, <b>14a</b>−<b>14c</b>, <b>15a</b>−<b>15c</b>, <b>16a</b>, <b>23a</b>−<b>23c</b>, <b>24a</b>−<b>24c</b>, <b>25a</b>−<b>25c</b>) and 1,4-disubstituted (<b>34a</b>−<b>34c</b> and <b>35a</b>−<b>35c</b>) 1,2,3-triazole rings were synthesized. The most potent cytotoxic effect on colorectal adenocarcinoma (SW620) was exerted by the 6-chloro-7-deazapurine <b>11c</b> (IC₅₀ = 9.07 µM), 6-chloropurine <b>13a</b> (IC₅₀ = 14.38 µM) and <b>15b</b> (IC₅₀ = 15.50 µM) ferrocenylalkyl derivatives. The <i>N</i>-9 isomer of 6-chloropurine <b>13a</b> containing ferrocenylmethylene unit showed a favourable in vitro physicochemical and ADME properties including high solubility, moderate permeability and good metabolic stability in human liver microsomes.