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Inhibition of thymidylate synthase by pergularinine, tylophorinidine and deoxytubulosine

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Title Inhibition of thymidylate synthase by pergularinine, tylophorinidine and deoxytubulosine
 
Creator Rao, K Narasimha
Bhattacharya, R K
Veankatachalam, S R
 
Description 442-448
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).

 
 
Date 2012-12-31T20:09:49Z
2012-12-31T20:09:49Z
1999-12
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/15477
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.36(6) [December 1999]