Bioactivity of miltefosine against aquatic stages of Schistosoma mansoni, Schistosoma haematobium and their snail hosts, supported by scanning electron microscopy

被引:47
作者
Eissa, Maha M. [1 ]
El Bardicy, Samia [2 ]
Tadros, Menerva [2 ]
机构
[1] Univ Alexandria, Dept Med Parasitol, Fac Med, Alexandria, Egypt
[2] Theodor Bilharz Res Inst, Dept Med Malacol, Cairo, Egypt
关键词
IN-VITRO ACTIVITY; HEXADECYLPHOSPHOCHOLINE MILTEFOSINE; STANDARD TREATMENT; PRAZIQUANTEL; RESISTANCE; ALKYLLYSOPHOSPHOLIPIDS; LEISHMANIA; FAILURE; STRAINS; DAMAGE;
D O I
10.1186/1756-3305-4-73
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
Background: Miltefosine, which is the first oral drug licensed for the treatment of leishmaniasis, was recently reported to be a promising lead compound for the synthesis of novel antischistosomal derivatives with potent activity in vivo against different developmental stages of Schistosoma mansoni. In this paper an in vitro study was carried out to investigate whether it has a biocidal activity against the aquatic stages of Schistosoma mansoni and its snail intermediate host, Biomphalaria alexandrina, thus being also a molluscicide. Additionally, to see whether miltefosine can have a broad spectrum antischistosomal activity, a similar in vitro study was carried out on the adult stage of Schistosoma haematobium, the second major human species, its larval stages and snail intermediate host, Bulinus truncutes. This was checked by scanning electron microscopy. Results: Miltefosine proved to have in vitro ovicidal, schistolarvicidal and lethal activity on adult worms of both Schistosoma species and has considerable molluscicidal activity on their snail hosts. Scanning electron microscopy revealed several morphological changes on the different stages of the parasite and on the soft body of the snail, which further strengthens the current evidence of miltefosine's activity. This is the first report of mollusicidal activity of miltefosine and its in vitro schistosomicidal activity against S. haematobium. Conclusions: This study highlights miltefosine not only as a potential promising lead compound for the synthesis of novel broad spectrum schistosomicidal derivatives, but also for molluscicidals.
引用
收藏
页数:11
相关论文
共 54 条
[1]   Short report:: Failure of standard treatment with praziquantel in two returned travelers with Schistosoma haematobium infection [J].
Alonso, D ;
Muñoz, J ;
Gascón, J ;
Valls, ME ;
Corachan, M .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2006, 74 (02) :342-344
[2]   Mapping and sequencing of acetylcholinesterase genes from the platyhelminth blood fluke Schistosoma [J].
Bentley, GN ;
Jones, AK ;
Agnew, A .
GENE, 2003, 314 :103-112
[3]   Development of miltefosine for the leishmaniases [J].
Berman, JD .
MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2006, 6 (02) :145-151
[4]  
BINDAJEM SM, 2007, J BASIC APPL SCI, V1, P776
[5]   In vitro activity of hexadecylphosphocholine (miltefosine) against metronidazole-resistant and -susceptible strains of Trichomonas vaginalis [J].
Blaha, C ;
Duchêne, M ;
Aspöck, H ;
Walochnik, J .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2006, 57 (02) :273-278
[6]   Praziquantel resistance [J].
Botros, Sanaa S. ;
Bennett, James L. .
EXPERT OPINION ON DRUG DISCOVERY, 2007, 2 :S35-S40
[7]   ANALOGS OF ALKYLLYSOPHOSPHOLIPIDS - CHEMISTRY, EFFECTS ON THE MOLECULAR-LEVEL AND THEIR CONSEQUENCES FOR NORMAL AND MALIGNANT-CELLS [J].
BRACHWITZ, H ;
VOLLGRAF, C .
PHARMACOLOGY & THERAPEUTICS, 1995, 66 (01) :39-82
[8]   Transmission electron microscopy of Schistosoma mansoni cercariae treated with hinokitiol (β-thujaplicin), a compound for potential skin application against cercarial penetration [J].
Chisty, MM ;
Nargis, M ;
Inaba, T ;
Ishita, K ;
Osanai, A ;
Kamiya, H .
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 202 (01) :63-67
[9]   Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy [J].
Chugh, Pauline ;
Bradel-Tretheway, Birgit ;
Monteiro-Filho, Carlos Mr ;
Planelles, Vicente ;
Maggirwar, Sanjay B. ;
Dewhurst, Stephen ;
Kim, Baek .
RETROVIROLOGY, 2008, 5 (1)
[10]   Miltefosine - discovery of the antileishmanial activity of phospholipid derivatives [J].
Croft, Simon L. ;
Engel, Juergen .
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 2006, 100 :S4-S8