Abstract:
:Beta-carboline-benzoquinolizidine plant alkaloid deoxytubulosine (DTB) was evaluated and assessed for the first 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 purified 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 30 microM for the cell growth and enzyme inhibitions, respectively). DTB concentrations >75 microM resulted in a total loss of the DHFR activity, thus suggesting that the beta-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 5x10(-6) M for DTB and that the enzyme inhibition is a simple linear 'non-competitive' type.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Rao KN,Venkatachalam SRdoi
10.1016/s0968-0896(98)00262-4subject
Has Abstractpub_date
1999-06-01 00:00:00pages
1105-10issue
6eissn
0968-0896issn
1464-3391pii
S0968-0896(98)00262-4journal_volume
7pub_type
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