Inhibition of growth and polyamines biosynthesis in P. falciparum by berenil and methylglyoxal bis (guanylhydrazone)
1
Issued Date
1988
Copyright Date
1988
Resource Type
Language
eng
File Type
application/pdf
No. of Pages/File Size
xiii, 133 leaves : ill.
Access Rights
open access
Rights
ผลงานนี้เป็นลิขสิทธิ์ของมหาวิทยาลัยมหิดล ขอสงวนไว้สำหรับเพื่อการศึกษาเท่านั้น ต้องอ้างอิงแหล่งที่มา ห้ามดัดแปลงเนื้อหา และห้ามนำไปใช้เพื่อการค้า
Rights Holder(s)
Mahidol University
Bibliographic Citation
Thesis (M.Sc. (Biochemistry))--Mahidol University, 1988
Suggested Citation
Darunee Tiravittayacom Inhibition of growth and polyamines biosynthesis in P. falciparum by berenil and methylglyoxal bis (guanylhydrazone). Thesis (M.Sc. (Biochemistry))--Mahidol University, 1988. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/103269
Title
Inhibition of growth and polyamines biosynthesis in P. falciparum by berenil and methylglyoxal bis (guanylhydrazone)
Alternative Title(s)
การยังยั้งการเจริญและการสังเคราะห์สารโปลีเอมีนส์ในเชื้อมาเลเรียชนิดฟัลซิพารั่มด้วยเบอรินีล และเม็ทธิลไกลออกซอล บิส (กวานิลไฮดราโซน)
Author(s)
Advisor(s)
Abstract
Berenil and MGBG, inhibitors of S-adenosylmethionine decarboxylase effectively inhibited growth of P. falciparum in culture with EC(,50) after 48 h exposure to the drugs of 0.41 and 2.4 ?M respectively. EC(,50) as determined by [(3)H] hypoxanthine uptake was 0.9 and 4.7 uM for berenil and MGBG respectively. Both drugs blocked development of the parasites from trophozoites to schizonts. Berenil and MGBG inhibited DNA, RNA and protein synthesis in P. falciparum. The EC(,50) for inhibiting these macromolecular synthesis of berenil was about 6-9 times higher than that of MGBG. Addition of exogenous polyamines, i.e., putrescine, spermidine or spermine at concentration of 1 mM could not reverse the inhibitory effects of berenil and MGBG on both growth and macromolecular synthesis of P. falciparum. P. falciparum contained 8-15% putrescine, 70-80% spermidine and 8-15% spermine and the concentrations of these polyamines were highest at schizont stage. Exposure of the parasites culture to berenil or MGBG resulted in a decrease in polyamine content in the parasites, especially spermidine decreased to 25% and 64% after exposure to 5 ?M berenil and 25 ?M MGBG for 30 h. Polyamine biosynthesis from either [(3)H] ornithine or [(14)C] putrescine in the parasites was inhibited by both berenil and MGBG. The results suggested that both drugs also inhibited the transport of [(14)C] putrescine from red cells into the parasites. These results suggested that inhibition of polyamines, especially spermidine biosynthesis by berenil and MGBG had led to inhibition of DNA, RNA and protein synthesis in P. falciparum, and as a result, growth of the parasites was inhibited. Nevertheless, the mechanism of actions of berenil and MGBG might not be specific to only polyamine biosynthesis, since the inhibitory effects of these drugs could not be reversed by addition of exogenous polyamines. Thus, berenil and MGBG might also inhibit growth of P. falciparum by other mechanisms which are still not known.
Description
Biochemistry (Mahidol University 1988)
Degree Name
Master of Science
Degree Level
Master's degree
Degree Department
Faculty of Science
Degree Discipline
Biochemistry
Degree Grantor(s)
Mahidol University