Dihydroethanoanthracene derivatives reverse in vitro quinoline resistance in Plasmodium falciparum malaria
Dihydroethanoanthracene derivatives reverse in vitro quinoline resistance in Plasmodium falciparum malaria
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DOI：
10.2174/157340608785700234
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发表时间：
2008-09-01
影响因子：
2.3
通讯作者：
Pradines, Bruno
中科院分区：
文献类型：
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作者：
Henry, Maud;Alibert, Sandrine;Pradines, Bruno
对27株恶性疟原虫分离株进行了体外逆转恶性疟原虫对氯喹（CQ）、奎宁（QN）、甲氟喹（MQ）和单去乙基氨基二喹（MDAQ）等喹啉类抗疟药物耐药性的10种分子的能力评估。其中4个化合物为9,10-二氢乙醇蒽衍生物（DEAs）。这些dea逆转了75%至92%的CQ耐药菌株。这些合成化合物与CQ联合使用比异拉帕米、酮替芬、氯丙嗪、利血平或尼卡地平更有效，后者逆转了不到50%的CQ耐药菌株。dea显著逆转了67%至100%的MDAQ耐药寄生虫。这些化合物与MDAQ联合使用比酮替芬（60%的逆转）、氯丙嗪（45%）、维拉帕米（33%）、利血平（30%）或尼卡地平（9%）更有效。无论测试何种分子，MQ耐药的逆转活性都不太明显，并且是均匀的，其率从酮替芬的42%到利血平、尼卡地平、维拉帕米和赛heptadine的58%不等。四种dea显著逆转了50%至55%对MQ具有耐药性的寄生虫。56 ~ 78%的QN耐药疟原虫被合成dea逆转。10种化合物对QN耐药菌株的逆转率差异不大，10种化学增敏剂的逆转率在56 ~ 78%之间。因此，dea与喹啉联合使用似乎是限制耐药菌株发展和治疗耐药地区患者的一种有希望的策略。
The capacity of ten molecules for reversing resistance in Plasmodium falciparum in vitro to quinoline antimalarial drugs, such as chloroquine (CQ), quinine (QN), mefloquine (MQ) and monodesethylamodiaquine (MDAQ), was assessed against 27 Plasmodium falciparum isolates. Four of these compounds were 9,10-dihydroethanoanthracene derivatives (DEAs). These DEAs reversed 75 to 92% of the CQ resistant strains. These synthetic compounds were more effective in combination with CQ than verapamil, ketotifen, chlorpromazine, reserpine or nicardipine, which reversed less than 50% of the CQ resistant strains. DEAs significantly reversed 67 to 100% of MDAQ resistant parasites. These compounds were more effective in combination with MDAQ than ketotifen (60% of reversal), chlorpromazine (45%), verapamil (33%), reserpine (30%) or nicardipine (9%). The reversal activity of MQ resistance was less pronounced, regardless of the molecule tested, and was homogeneous with a rate ranging from 42% for ketotifen to 58% for reserpine, nicardipine, verapamil and cyproheptadine. The four DEAs significantly reversed 50 to 55% of the parasites resistant to MQ. Fifty-six to 78% of the QN resistant parasites were reversed by the synthetic DEAs. There were few differences in the rate of reversal activity on QN resistant strains between the ten compounds, with rates ranging between 56 to 78% for the ten chemosensitizers. The use of DEAs in combination with quinoline seems to be thus a promising strategy for limiting the development of drug resistant strains and for treating patients in drug resistant areas.