In the present investigation, a series of novel N-substituted 5-arylidenerhodanine was designed and further synthesized from their corresponding aromatic aldehydes according to Knoevenagel�s condensation method in microwave conditions. The resulting 5-arylidinerhodanine was reacted with 2-phenylethyl chloride in presence of potassium carbonate and dimethyl formamide under microwave conditions to give N-substituted 5-arylidenerhodanine. The synthesized compounds were confirmed on the basis of spectral data and elemental analyses. The synthesized compounds evaluated for their cytotoxic activity against two different human cancer cell lines using MTT assay. The cytotoxic activity results revealed that the synthesized compounds demonstrated the ability to inhibit HT-29 (colon cancer), MCF-7 (breast cancer) cancer cell lines against reference drug Methotrexate. Among the compounds tested, the most active compounds (4-trifluoro and 3-fluoro-substituted) possess significant cytotoxic activity against both the cancer cell lines and all other compounds showed moderate to weak activity.
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