In vitro anti-leishmanial activities and structure-activity relationship analysis of new antimony(III) complexes

1609-1617New fourteen antimony(III) complexes of general formula [SbLnCl3] (where n= 1 or 2, L =2-aminopyridine, 5-methyl-2-aminopyridine, 2-aminopyrimidine, 4,6-dimethoxy-2-aminopyrimidine, 2-benzyl-2-thiopseudeourea,2-guanidinobenzimidazole, 2-amino-5-thiol-4,6-dimethoxypyrimidine, 2-amino-5-(1H-tetrazol-5-ylthio)-4,6-dimethoxypyrimidine, N-2-pyrimidine, 2-piperidinecarboxamide, N-2-pyrimidine, 2-pyrrolidinecarboxamide, 2-amino-5-(1H-tetrazol-5-iltiyo)-4,6-dimethoxypyrimidine-2-pyrrolidinecarboxamide and N-2-pyrimidine, 5-chloro-2-thiophenecarboxamide, N-2-benzothiazol-2-pyrrolidinecarboxaamide, N,N-(1,2-phenyl)dipyrrolidine-2-carboxamide) have been synthesized and their anti-leishmanial activity have been assessed in vitro against Leishmania tropica promastigotes. The best complex, Sb(2-guanidinobenzimidazole)Cl3 is demostrated 3.16% growth inhibition at a concentration of 31.25 μg/mL. In general, antimony(III) complexes containing pyrimidine ligands has showed higher anti-leishmanial activity than antimony(III) complexes bearing pyridine ligands, and electron-donating substituents decrease the anti-leishmanial activity. All complexes have been optimised with DFT/B3LYP/LANL2DZ method in the gas phase. Several descriptors are tested to find a quantitative correlation between anti-leishmanial activity and structural properties of the complexes by best multiple linear regression method. Good correlations are obtained with minimum net atomic charge for a C atom and maximum bond order of a Cl atom. The developed QSAR equation is internally validated

In vitro anti-leishmanial activities and structure-activity relationship analysis of new antimony(III) complexes

New fourteen antimony(III) complexes of general formula [SbLnCl3] (where n= 1 or 2, L =2-aminopyridine, 5-methyl-2-aminopyridine, 2-aminopyrimidine, 4,6-dimethoxy-2-aminopyrimidine, 2-benzyl-2-thiopseudeourea,2-guanidinobenzimidazole, 2-amino-5-thiol-4,6-dimethoxypyrimidine, 2-amino-5-(1H-tetrazol-5-ylthio)-4,6-dimethoxypyrimidine, N-2-pyrimidine, 2-piperidinecarboxamide, N-2-pyrimidine, 2-pyrrolidinecarboxamide, 2-amino-5-(1H-tetrazol-5-iltiyo)-4,6-dimethoxypyrimidine-2-pyrrolidinecarboxamide and N-2-pyrimidine, 5-chloro-2-thiophenecarboxamide, N-2-benzothiazol-2-pyrrolidinecarboxaamide, N,N-(1,2-phenyl)dipyrrolidine-2-carboxamide) have been synthesized and their anti-leishmanial activity have been assessed in vitro against Leishmania tropica promastigotes. The best complex, Sb(2-guanidinobenzimidazole)Cl3 is demostrated 3.16% growth inhibition at a concentration of 31.25 μg/mL. In general, antimony(III) complexes containing pyrimidine ligands has showed higher anti-leishmanial activity than antimony(III) complexes bearing pyridine ligands, and electron-donating substituents decrease the anti-leishmanial activity. All complexes have been optimised with DFT/B3LYP/LANL2DZ method in the gas phase. Several descriptors are tested to find a quantitative correlation between anti-leishmanial activity and structural properties of the complexes by best multiple linear regression method. Good correlations are obtained with minimum net atomic charge for a C atom and maximum bond order of a Cl atom. The developed QSAR equation is internally validated

Arbutus unedo L.: Chemical and Biological Properties

Arbutus unedo L. (strawberry tree) has a circum-Mediterranean distribution, being found in western, central and southern Europe, north-eastern Africa (excluding Egypt and Libya) and the Canary Islands and western Asia. Fruits of the strawberry tree are generally used for preparing alcoholic drinks (wines, liqueurs and brandies), jams, jellies and marmalades, and less frequently eaten as fresh fruit, despite their pleasing appearance. An overview of the chemical composition of different parts of the plant, strawberry tree honey and strawberry tree brandy will be presented. The biological properties of the different parts of A. unedo and strawberry tree honey will be also overviewed

Multilocus Microsatellite Typing (MLMT) of Strains from Turkey and Cyprus Reveals a Novel Monophyletic L. donovani Sensu Lato Group

In eastern Mediterranean, leishmaniasis represents a major public health problem with considerable impact on morbidity and potential to spread. Cutaneous leishmaniasis (CL) caused by L. major or L. tropica accounts for most cases in this region although visceral leishmaniasis (VL) caused by L. infantum is also common. New foci of human CL caused by L. donovani complex strains were recently described in Cyprus and Turkey. Herein we analyzed Turkish strains from human CL foci in Çukurova region (north of Cyprus) and a human VL case in Kuşadasi. These were compared to Cypriot strains that were previously typed by Multilocus Enzyme Electrophoresis (MLEE) as L. donovani MON-37. Nevertheless, they were found genetically distinct from MON-37 strains of other regions and therefore their origin remained enigmatic. A population study was performed by Multilocus Microsatellite Typing (MLMT) and the profile of the Turkish strains was compared to previously analyzed L. donovani complex strains. Our results revealed close genetic relationship between Turkish and Cypriot strains, which form a genetically distinct L. infantum monophyletic group, suggesting that Cypriot strains may originate from Turkey. Our analysis indicates that the epidemiology of leishmaniasis in this region is more complicated than originally thought

MIKROBIYOLOJI BULTENI

Cutaneous leishmaniasis (CL) is a parasitic disease transmitted by vector sand flies Phlebotomus and Lutzomyia. This disease is characterized by long time non-healing skin lesions, and caused by Leishmania species. CL is the most common infection in Eastern and Southeastern Anatolia in Turkey and L. tropica is known as the main agent of the disease. Number of cases is increasing in our country in time because of malnutrition, migration, travel, low socioeconomic level and ecological changes. For the treatment, the pentavalent antimonials are often used as intralesionally for many years, and it was reported that resistant cases have increased in recent years. New treatment methods and anti-Leishmanial activity of new agents have been investigated because of side effects, resistance development and toxic reactions of the present drugs. These studies are first carried out in vitro and afterwards with in vivo experimental animal models. Reporter gene technology has been used to investigate a variety of purposes like biological events in microorganisms and the efficacy and resistance of drugs in recent years. The major areas that green fluorescent protein (gfp) used are that they can be incorporated into different genes to determine the amount of expression of these genes in different organisms and can be used as markers in living cells. Especially gfp gene, which encodes the green fluorescent protein, is widely used nowadays. Gene-based assays have several advantages like being easy to follow-up, inexpensive and have improved biosecurity. The aim of the present study was to perform the transfection of L. tropica with enhanced gfp (egfp) and in vitro usefulness of gfp-transfectants as a drug screening model in comparison to the conventional methods. Promastigotes of L. tropica were transfected with p6.5/egfp by electroporation and selected for tunicamycin-resistance as previously described. L. tropica promastigotes transfected with gfp and in vitro effect of meglumine animoniate was assessed using different methods such as fluorescence microscopy, fluorometer and XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide) assay. The use of gfp-transfected Leishmania strains was found more rapid and more sensitive by fluorescent microscopy and fluorometry than conventional assays for the evaluation of potential anti-leishmanial agents. Consequently, stable gfp-transfected Leishmania species will be used in vitro and in vivo for screening of anti-leishmanial drugs and vaccine development as well as for understanding the biology of the host-parasite interactions at the cellular level. As a result ot this study, gfp transfected model using a Turkish L. tropica isolate was established to be used in further studies

ACTA TROPICA

In the present study, we aimed to carry out an epidemiological and entomological survey on a visceral leishmaniasis (VL) focus located on the northern central part of Anatolia, Turkey. Five villages of Corum province, where five confirmed cases of human visceral leishmaniasis (HVL) (one patient/village) were reported between June 1998 and August 2001 were included in the study. A total of 625 children and 131 dogs were sampled and the physical examination was carried out by authorized physicians and veterinarians. An indirect fluorescent antibody test (IFAT) was performed by standard procedures for human and dog sera, while the direct agglutination test (DAT) was only performed for dog sera. Sand fly collection was performed in three villages by CDC miniature light traps. Hepatosplenornegaly and hepatomegaly were detected in two and eight children, respectively. The seropositivity rate among children was found to be 0.16% (1/625) in the region. The seroprevalence of canine infection in these five villages ranged between 0.0% and 28.26%. In two villages, named Ahlatcik and Asagifindikli, no seropositive dogs were found. A total of 1218 sand flies were collected throughout the study. Six species of Phlebotonius were identified: P. transcaucasicus, P. neglectus, P. halepensis, P tobbi, P. papatasi, and P. jacusieli. P. transcaucasicus was found to be the predominant species in Cevizli (47.44%; 343/723) and Ucoluk (79.95%; 351/439) villages, while P. tobbi was abundant in Kucukerikli (42.85%; 24/56). (c) 2005 Elsevier B.V. All rights reserved

Echinococcus granulosus protoskolekslerinden in vitro mikrokist geliştirilmesi ve albendazole ve mebendazole'ün mikrokistler üzerindeki in vitro etkinliğinin araştırılması

Bu tezin, veri tabanı üzerinden yayınlanma izni bulunmamaktadır. Yayınlanma izni olmayan tezlerin basılı kopyalarına Üniversite kütüphaneniz aracılığıyla (TÜBESS üzerinden) erişebilirsiniz.ÖZET Kistik ekinokokkozis (CE), E. granulosus' un larval formunun sebep olduğu zoonotik bir enfeksiyondur. Türkiye'nin de dahil olduğu dünyanın pek çok bölgesinde halen önemli bir halk sağlığı ve ekonomik problem olarak karşımıza çıkmaktadır. Günümüzde cerrahi girişim CE tedavisinde halen asıl tedavidir. Benzimidazole türevlerinden Albendazole ve Mebendazole'ün, son yıllarda hidatik kist tedavisinde cerrahiye yardımcı veya alternatif olarak kullanımı ile ilgili çalışmalar yapılmaktadır. Bu çalışmada, E.granulosus protoskolekslerinden in vitro besiyeri ortamında 3 ayda minyatür hidatik kistler geliştirilmiş ve bu kistler üzerinde Albendazole ve Mebendazole'ün in vitro etkileri araştırılmıştır. Her iki ilacın da minyatür hidatik kistler üzerinde etkinlik gösterdiği, Albendazole ile Mebandazole karşılaştırıldığında ise; sadece düşük dozda 7'inci günde fark bulunamazken, 15'inci ve 30'uncu günlerde Albendazole'ün daha etkili olduğu gözlenmiştir. Minyatür hidatik kistlerin ilaç araştırmaları ve deneysel çalışmalarda kullanılabilecek in vitro bir model olabileceği sonucuna varılmıştırSUMMARY Human cystic echinococcosis (CE) is a zoonotic infection caused by larval forms (metacestodes) of E.granulosus. CE is still an important public health and economic problem in many parts of the world including Turkey. Surgical intervention is still the treatment of choice for CE. Recent years, the chemoterapeutic treatment of hydatid disease in man, as an supplementary or alternative surgery, has been widely studied using the Benzimidazole derivates, Albendazole and Mebendazole. In this study, the miniature hydatid cysts were developed in culture media from E.granulosus protoscolices and in vitro efficacy of Albendazole and Mebendazole were investigated on miniature hydatid cysts. Both of drugs were found effective on miniature hydatid cysts. When Albendazole and Mebendazole were compared with each other; although there was no statistically significant difference between low doses on 7th days, on 15th and 30th days Albendazole treatments were found more effective than the others. As a result of this study, the miniature hydatid cysts can be used as an in vitro model for drug investigations and experimental studies in future