کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10027995 | 1591923 | 2005 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Antiproliferative synergism of azasterols and antifolates against Toxoplasma gondii
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موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
میکروبیولوژی و بیوتکنولوژی کاربردی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Antiproliferative synergism of azasterols and antifolates against Toxoplasma gondii Antiproliferative synergism of azasterols and antifolates against Toxoplasma gondii](/preview/png/10027995.png)
چکیده انگلیسی
The antiproliferative effects of two azasterols, 22,26-azasterol (20-piperidin-2-yl-5α-pregnan-3β-20(R,S)-diol, AZA) and 24,25(R,S)-epiminolanosterol (EIL), in combination with sulphadiazine (SDZ) and pyrimethamine (PYR) were studied against Toxoplasma gondii tachyzoites growing in cultured mammalian cells. We had previously shown that AZA and EIL, two known inhibitors of Î24(25)sterol methyl transferase in fungi and protozoa, have a potent and selective anti-T. gondii activity, although no 24-alkyl sterols have been detected in this parasite. We now report that when these sterol analogues were used in combination with the conventional SDZ/PYR treatment, potent synergistic effects were observed, ranging from 10- to 100-fold reductions of the IC50 values in the presence of sub-optimal doses of azasterols. When exposed to these drug combinations, intracellular T. gondii parasites displayed diverse subcellular alterations, including mitochondrial swelling, the arrest of the endodiogeny process with fragmented nuclei and subsequent cell lysis. These results suggest a potential new approach for the treatment of toxoplasmosis, which could significantly lower the required levels of antifolates and thus their adverse side effects.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Antimicrobial Agents - Volume 25, Issue 2, February 2005, Pages 130-135
Journal: International Journal of Antimicrobial Agents - Volume 25, Issue 2, February 2005, Pages 130-135
نویسندگان
Lucas Dantas-Leite, Julio A. Urbina, Wanderley de Souza, Rossiane C. Vommaro,