The phenanthroindolizidine plant alkaloids pergularinine (PGL) and tylophorinidine (TPD) isolated from the Indian medicinal herb Pergularia pallida have been evaluated for their biological activity and assessed for the first time employing dihydrofolate reductase as the probe in the present investigations. The enzyme is a key target in cancer chemotherapy and has been purified from Lactobacillus leichmannii. Cytotoxicity studies showed that both PGL and TPD are potently toxic and inhibited the growth of L. leichmannii cells. Both the alkaloids significantly inhibited DHFR activity. Alkaloid concentrations greater than 75-95 microM resulted in a complete loss of DHFR activity. Our results are suggestive of the alkaloids as potential antimicrobial and antitumour compounds. Alkaloid binding to DHFR is slow and reversible.
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