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

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

Evaluation of antigenic variations between two virulent toxoplasma strains

Toxoplasma gondii infection in humans is routinely assessed by serological means. Here, the authors attempted to compare the response of different Toxoplasma strains to serological tests and to evaluate the antigenic profiles of the RH and RH Ankara (TRH) strains with Western blotting. Anti-Toxoplasma IgG antibodies of 72 patients were examined with the indirect immunofluorescence antibody (IFA) test, ELISA and Western blotting (WB) by using antigen from both strains. Antigenic variations between strains did not affect IFA and ELISA test results, but qualitative and quantitative differences between the WB patterns were observed. A number of bands with molecular masses varying between 17 and 105 kDa were detected in WB. Fourteen different bands were obtained with the assay performed with RH strain antigen. An additional four bands were observed with TRH strain antigen. Also, an 80 kDa band was observed to stain darker in the blot with TRH strain antigen, whereas with RH strain antigen 30 and 38 kDa bands were darker. The results showed that strain-specific polymorphism in tachyzoite antigens of different Toxoplasma strains is important in the evaluation of WB but not in conventional serological analyses such as ELISA and IFA

Assessment of the Effects of Extremely Low Frequency Electromagnetic Fields on Toxoplasma gondii

Background: The effects of extremely low frequency electromagnetic fields (ELF-EMF) on Toxoplasma gondii have not been explained yet. The aim of this study was to assess the possible effects of ELF-EMF on growth, survival time and viability of Toxoplasma gondii. In addition, the life span of Toxoplasma infected animals was investigated. Methods: Sixty adult male BALB/c mice were used for in vivo and in vivo experiments in Laboratory of Biopyhsics and Parasitology of Medical Faculty, Adnan Menderes University, Turkey, in 2010. During in vivo experiments, pulsed and continuous EMFs were applied for 5 d to the infected mice. During in vivo experiments, pulsed and continuous EMF was applied to the tachyzoites within peritoneal exudates for 8 h/d at 4 °C and the tachyzoites were then injected to mice. In both experiments, the number of T. gondii in peritoneal exudates was counted and T. gondii protein bands patterns were investigated with polyacrylamide gel electrophoresis and Western Blotting. Results: Pulsed and continuous EMF exposure reduced the number of T. gondii tachyzoites in comparison to controls. However, no statistically significant differences were observed at the patterns of protein bands among the samples. Conclusion: EMF exposure induces a decrease in the number of T. gondii. Further studies are required to understand the mechanism of EMF on intracellular parasites

In vitro activity of arbutus unedo leaf extracts against trichomonas vaginalis trophozoitesi

Trichomonas vaginalis (T. vaginalis) sık görülen, cinsel yolla bulaşan kamçılı bir protozoondur. T. vaginalis infeksiyonu 5- nitroimidazol türevleri ile tedavi edilmektedir. Bununla birlikte ilaca karşı direnç uzun zamandır bilinmekte ve yeni alternatifler araştırılmaktadır. Arbutus unedo özellikle Güney Avrupa'da kayalık ve makili alanda yetişen doğal bir bitkidir. Bu çalışmada Arbutus unedo yapraklarında hazırlanan etanol, su, heksan ve etil asetat ekstrelerinin T. vaginalis trofozoitleri üzerine in vitro etkileri araştırılmış ve etil asetat ekstresinin etkili olduğu saptanmıştır (etil asetat ekstresinin 500 ?g/ml'lik konsantrasyonda çoğalmayı engelleyici etkisinin %100 olduğu saptanmıştır). Bu ekstrenin ileride umut verici anti-trichomonasidal bir ajan olabileceği ve ileri araştırmaların yapılması gerektiği düşünülmüştür.Trichomonas vaginalis (T. vaginalis) is a flagellated protozoan commonly causing sexually transmitted disease. T. vaginalis infections are treated with a 5-nitroimidazole derivate. However, drug resistance has been known to occur for a long time and new alternatives are under investigation. Arbutus unedo is a wild plant mainly growing in maquis and rocky places of the seaboard in Southern Europe. In our study, ethanolic, water, hexane and ethyl acetate extracts of Arbutus unedo leaves were tested in vitro against T.vaginalis trophozoites and the ethyl acetate extract of Arbutus unedo leaves was found to be effective (Growth inhibition rate (GI): 100%, at the concentration of 500 ;amp;#956;g/ml). It may be a promising anti-trichomonacidal agent in the future and further experiments are needed