氯喹曾經(jīng)是對付瘧疾的特效藥物，可隨著瘧原蟲的耐藥性不斷增加,，氯喹也被人們?nèi)諠u忽視,。但是新的研究表明，它仍然能夠在對付瘧疾的戰(zhàn)役中發(fā)揮重要作用,。
通過把氯喹與其它化合物結(jié)合在一起,，科學(xué)家已經(jīng)讓這種藥物對甚至對氯喹具有耐藥性的瘧疾仍然有效。這項由美國波特蘭州立大學(xué)David Peyton領(lǐng)導(dǎo)的研究發(fā)表在8月12日的《藥物化學(xué)雜志》（Journal of Medical Chemistry）上,。
自從上個世紀90年代以來,，科學(xué)家們已經(jīng)試驗了各種可能抑制耐藥瘧疾蛋白的化合物。Peyton的研究組把一種“逆轉(zhuǎn)劑”（reversal agents）附著在氯喹分子上,，使之產(chǎn)生一種單一混合物分子,。隨后，Peyton等人測試了這種分子在實驗室中對惡性瘧原蟲（Plasmodium falciparum）的有效性,。
讓人鼓舞的情況出現(xiàn)了,。這種“逆轉(zhuǎn)性氯喹”對于耐氯喹的瘧原蟲的效果，至少與氯喹對付不具有氯喹耐性的瘧原蟲的效果一樣,。在被夏氏瘧原蟲(Plasmodium chabaudi)感染的老鼠身上,，這種藥物也表現(xiàn)出同樣的效果。夏氏瘧原蟲在嚙齒動物身上引發(fā)瘧疾,。這種藥物沒有明顯的副作用,。
Peyton指出,，盡管好幾種化合物都發(fā)揮了逆轉(zhuǎn)劑的作用,，它們所需的劑量通過都比逆轉(zhuǎn)性氯喹高。目前,，Peyton的研究組正在開發(fā)質(zhì)量更好的相關(guān)分子,。
英國倫敦圣喬治醫(yī)院醫(yī)學(xué)院寄生蟲病教授Sanjeev Krishna表示，對付耐藥性瘧疾的各種手段都應(yīng)該嘗試,。但是他指出,，一種富有希望的化合物是否會進入藥物開發(fā)階段，這要依靠各種因素,，諸如成本,，生產(chǎn)的容易程度以及服用該化合物后它如何發(fā)揮作用,。
英文原文：
Hybrid molecule could treat drug resistant malaria
A drug that was one of the main tools for treating malaria until the parasite grew resistant to it could still have a major role in fighting the disease.
Researchers have made the drug — chloroquine — effective against even chloroquine-resistant malaria by binding it with another chemical. The research, led by David Peyton of Portland State University, United States, was published on 12 August in the Journal of Medical Chemistry.
Since the 1990s, researchers have been experimenting with chemicals that seem to block the malarial proteins that confer drug resistance.
Peyton's team attached one of these 'reversal agents' to chloroquine to produce a single hybrid molecule. They then tested its effectiveness against the malaria parasite Plasmodium falciparum in the laboratory.
The 'reversed chloroquine' was at least as effective against chloroquine-resistant parasites as chloroquine is against non-resistant malaria.
The drug was also effective in mice infected with Plasmodium chabaudi, which causes malaria in rodents. There were no obvious side effects.
Peyton said that, although several chemicals act as reversal agents, the doses needed are generally higher than with reversed chloroquine. His team is currently developing related molecules with improved qualities.
Sanjeev Krishna, a professor of parasitology at St. George's Hospital Medical School in London, United Kingdom, says that different approaches to the problem of drug-resistant malaria are always welcome.
But he points out that whether a promising compound enters drug development would depend on factors such as the cost and ease of producing it, and how the chemical acts when taken.
