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Title: Inhibition of thymidylate synthase by pergularinine, tylophorinidine and deoxytubulosine
Authors: Rao, K Narasimha
Bhattacharya, R K
Veankatachalam, S R
Issue Date: Dec-1999
Publisher: NISCAIR-CSIR, India
Abstract: The activity of thymidylate synthase (TS) purified in our laboratory from Lactobacillus leichmannii was inhibited by pergularinine (PGL) and tylophorinidine (TPD) and deoxytubulosine (DTB) isolated froml the Indian medicine plants Pergularia pallida and Alanguml lamarckii respectively. Cytotoxicity studies showed that cell growth of L. leichmannii was inhibited (IC50) = 40-45 μM) by all the three alkaloids, the concentrations > 80-90 μM resulting in complete loss of the enzyme activit y. Ki values of the enzyme calculated from Lineweaver-Burk and Dixon plots for PGL, TPD and DTB were l0× 10-6M, 9× 10-6M  and 7× 10-6M  respectively. These are typed as ‘non-competitive’ inhibitors of TS. All the three alkaloids, inhibited (IC50 = 50 μM) the elevated TS activity of leukocytes in cancer patients with clinically diagnosed chronic myelocytic leukemia (n= 10), acute lymphocytic leukemia (n=8) and metastatic solid tumours (n=3).  
Page(s): 442-448
ISSN: 0975-0959 (Online); 0301-1208 (Print)
Appears in Collections:IJBB Vol.36(6) [December 1999]

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