Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Due to the emergence of multidrug resistance of malaria parasites, there is an urgent need to modify existing antimalarial drugs through structural changes as well as to search new pharmacophores to counteract the induced resistance. In the present work, different quantitative structure-activity relationship (QSAR) models have been developed using a series of 73 1,2,3,4-tetrahydroacridin-9(10H)-one (THA) analogs with well defined antimalarial activity against W2 clone to provide detailed insight into the main structural fragments that impart antimalarial activity to these molecules. To the best of our knowledge, this is first QSAR report of THA analogs as antimalarials. From the developed models, it may be inferred that for an enhancement in the antimalarial activity of the molecules: i) R2 position should be substituted with a bulky group (like phenyl, methoxy, isopropyl, tertiary butyl group) which may be further substituted with electrostatically favored positively charged group; ii) R3 position should be substituted with hydrophobically favored but sterically disfavored group; iii) R4 position should be substituted with positively charged group lacking any carbon atom and iv) R5 position should be substituted with two methyl groups. On the contrary, substitution with bulky group at R6 position may reduce the antimalarial activity. Using the developed models, we have designed and proposed some new compounds which showed good in silico predicted activity. The designed compounds may be experimentally proved to be active and useful THA derivatives as antimalarial compounds.
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PMID:First report on exploring structural requirements of 1,2,3,4- tetrahydroacridin-9(10H)-one analogs as antimalarials using multiple QSAR approaches: descriptor-based QSAR, CoMFA-CoMSIA 3DQSAR, HQSAR and G-QSAR approaches. 2312 58

Malaria kills approximately 1 million people a year, mainly in sub-Saharan Africa. Essential steps in the life cycle of the parasite are the development of gametocytes, as well as the formation of oocysts and sporozoites, in the Anopheles mosquito vector. Preventing transmission of malaria through the mosquito is necessary for the control of the disease; nevertheless, the vast majority of drugs in use act primarily against the blood stages. The study described herein focuses on the assessment of the transmission-blocking activities of potent antierythrocytic stage agents derived from the 4(1H)-quinolone scaffold. In particular, three 3-alkyl- or 3-phenyl-4(1H)-quinolones (P4Qs), one 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), and one 1,2,3,4-tetrahydroacridin-9(10H)-one (THA) were assessed for their transmission-blocking activity against the mosquito stages of the human malaria parasite (Plasmodium falciparum) and the rodent parasite (P. berghei). Results showed that all of the experimental compounds reduced or prevented the exflagellation of male gametocytes and, more importantly, prevented parasite transmission to the mosquito vector. Additionally, treatment with ICI 56,780 reduced the number of sporozoites that reached the Anopheles salivary glands. These findings suggest that 4(1H)-quinolones, which have activity against the blood stages, can also prevent the transmission of Plasmodium to the mosquito and, hence, are potentially important drug candidates to eradicate malaria.
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PMID:4-(1H)-Quinolones and 1,2,3,4-Tetrahydroacridin-9(10H)-ones prevent the transmission of Plasmodium falciparum to Anopheles freeborni. 2408 Jun 48