Pii: S0968-0896(98)00262-4
نویسندگان
چکیده
Ðb-Carboline-benzoquinolizidine plant alkaloid deoxytubulosine (DTB) was evaluated and assessed for the ®rst time for its biochemical and biological activity employing the biomarker dihydrofolate reductase (DHFR) (5,6,7,8-tetrahydrofolate: NADP oxidoreductase, EC 1.5.1.3) as the probe enzyme, a key target in cancer chemotherapy. DHFR, employed in the present investigations was puri®ed from Lactobacillus leichmannii. DTB, isolated from the Indian medicinal plant Alangium lamarckii was demonstrated to exhibit potent cytotoxicity. The alkaloid potently inhibited the cell growth of L. leichmannii and the cellular enzyme activity of DHFR (IC50=40 and 30mM for the cell growth and enzyme inhibitions, respectively). DTB concentrations >75mM resulted in a total loss of the DHFR activity, thus suggesting that the b-carboline-benzoquinolizidine plant alkaloid is a promising potential antitumor agent. Our results are also suggestive of its potential antimicrobial activity. DTB binding to DHFR appears to be slow and reversible. Inhibition kinetics revealed that DHFR has a Ki value of 5 10ÿ6M for DTB and that the enzyme inhibition is a simple linear `non-competitive' type. # 1999 Elsevier Science Ltd. All rights reserved.
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