Faculty of Science - Mahidol University

Mahidol University Annual Research Abstracts, Vol. 33 281
Vanillin, a food flavoring agent, has been reported to show
anti-mutagenic activity and to inhibit chemical carcinogenesis. In
this study, we examined the effect of vanillin on the growth and
metastasis of 4T1 mammary adenocarcinoma cells in BALB/c mice.
Mice orally administered with vanillin showed significantly reduced
numbers of lung metastasized colonies compared to controls. In
vitro studies revealed that vanillin, at concentrations that were not
cytotoxic, inhibited invasion and migration of cancer cells and
inhibited enzymatic activity of MMP-9 secreted by the cancer cells.
Vanillin also showed growth inhibitory effect towards cancer cells
in vitro. However, vanillic acid, a major metabolic product of vanillin
in human and rat, was not active in these in vitro activity assays.
Our findings suggest that vanillin has anti-metastatic potential by
decreasing invasiveness of cancer cells. Since vanillin is generally
regarded as safe, it may be of value in the development of antimetastatic
drugs for cancer treatment.
(Published in Eur J Pharm Sci 2005; 25: 57-65. Supported by JSPS-
NRCT Collaborative Scientific Research Fellowship Program.)
RETROSPECTIVE STUDY OF PATIENTS WITH
SUSPECTED INBORN ERRORS OF METABOLISM
AT SIRIRAJ HOSPITAL, BANGKOK, THAILAND
(1997-2001) (NO. 724)
Wasant P 1 , Vatanavicharn N 1 , Srisomsap C 2 , Sawangareetrakul
P 2 , Liammongkolkul S 1 , Svasi J 3 .
1 Department of Pediatrics, Faculty of Medicine, Siriraj Hospital,
Mahidol University, Bangkok; 2 Laboratory of Biochemistry,
Chulabhorn Research Institute, Bangkok; 3 Department of
Biochemistry, Faculty of Science, Mahidol University, Bangkok.
Key words : inborn errors of metabolism, quantitative plasma amino
acid analysis, Siriraj Hospital.
This retrospective clinical study was carried out with
suspected inborn errors of metabolism (IEM) at Siriraj Hospital
during 1997-2001. The authors investigated 114 patients by
quantitative plasma amino acid analysis. All patients were
categorized into 2 major groups: 1) positive diagnoses for IEM, 2)
negative diagnoses for IEM. The two groups were investigated,
studied including statistical analysis. The authors found that most
IEM ascertained through plasma amino acid analysis were smallmolecule
diseases (74.3%) and amino acid disorders consisted of
the most frequent disorders. The presented data demonstrated that
the ratio of positive diagnoses to all patients studied was 1:8.
Epidemiological data showed there were more male than female
patients. Onset of diseases occurred predominantly during the first
month of age, and was rarely found after 3 years of age. There were
histories of consanguinity in half of the IEM patients. The most
common presenting symptom was acute metabolic encephalopathy
and specific signs for small-molecule disorders included
hepatomegaly, unusual urine odor, acidosis, hyperammonemia,
alteration of consciousness, and ketosis/ketonurea. These signs or
symptoms indicated further metabolic investigations. Comparison
of the data from Thailand with other countries showed both
similarities and differences to the Caucasian population. Thus,
further studies in IEM are much needed for the Thai population.
(Published in J Med Assoc Thai 2005; 88: 746-53. Supported by
Chulabhorn Research Institute and Thailand Research Fund.)
MALARIAL (PLASMODIUM FALCIPARUM)
DIHYDROFOLATE REDUCTASE-THYMIDY-
LATE SYNTHASE: STRUCTURAL BASIS FOR
ANTIFOLATE RESISTANCE AND DEVELOP-
MENT OF EFFECTIVE INHIBITORS. (NO. 725)
Yuthavong Y 1 , Yuvaniyama J 2 , Chitnumsub P 1 , Vanichtanankul
J 1 , Chusacultanachai S 1 , Tarnchompoo B 1 , Vilaivan T 3 ,
Kamchonwongpaisan S 1 .
1 National Center for Genetic Engineering and Biotechnology,
National Science and Technology Development Agency,
Pathumthani; 2 Center of Excellence for Protein Structure and
Function and Department of Biochemistry, Faculty of Science,
Mahidol University, Bangkok; 3 Department of Chemistry,
Faculty of Science, Chulalongkorn University, Bangkok .
Key words : dihydrofolate reductase, Plasmodium falciparum,
thymidylate synthase.
Dihydrofolate reductase-thymidylate synthase (DHFR-TS)
from Plasmodium falciparum, a validated target for antifolate
antimalarials, is a dimeric enzyme with interdomain interactions
significantly mediated by the junction region as well as the
Plasmodium-specific additional sequences (inserts) in the DHFR
domain. The X-ray structures of both the wild-type and mutant
enzymes associated with drug resistance, in complex with either a
drug which lost, or which still retains, effectiveness for the mutants,
reveal features which explain the basis of drug resistance resulting
from mutations around the active site . Binding of rigid inhibitors
like pyrimethamine and cycloguanil to the enzyme active site is
affected by steric conflict with the side -chains of mutated residues
108 and 16, as well as by changes in the main chain configuration.
The role of important residues on binding of inhibitors and substrates
was further elucidated by site-directed and random mutagenesis
studies. Guided by the active site structure and modes of inhibitor
binding, new inhibitors with high affinity against both wild-type
and mutant enzymes have been designed and synthesized, some of
which have very potent antimalarial activities against drug -resistant
P. falciparum bearing the mutant enzymes.
(Published in Parasitology 2005; 130: 249–59. Supported by Medicines
for Malaria Venture, EU INCO-DEV, Wellcome Trust, Thailand
Tropical Diseases Program and BIOTEC, NSTDA, Thailand .)
STOICHIOMETRIC SELECTION OF TIGHT-
BINDING INHIBITORS BY WILD-TYPE AND
MUTANT FORMS OF MALARIAL (PLASMODIUM
FALCIPARUM) DIHYDROFOLATE REDUCTASE.
(NO. 726)
Kamchonwongpaisan S 1 , Vanichtanankul J 1 , Tarnchompoo B 1 ,
Yuvaniyama J 2 , Taweechai S 1 , Yuthavong Y 1 .
1 National Center for Genetic Engineering and Biotechnology,
National Science and Technology Development Agency,
Pathumthani; 2 Department of Biochemistry, Faculty of Science,
Mahidol University, Bangkok.
Key words : dihydrofolate reductase, Plasmodium falciparum, tightbinding
inhibitors.
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