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Background: We report the design, synthesis and evaluation of a series of 4-biaryl substituted 2-amino benzo[h]chromene derivatives as potential cytotoxic agents. Methods: The one-pot synthesis of this class of compounds was carried out under ultrasound irradiation using an MCR involving Pd/C-catalyzed Suzuki-Miyaura coupling as a key step. Result and Conclusion: Several of these compounds showed promising cytotoxicities when tested against cancer cell lines but no or little effects on non-cancerous cell lines.