Ali Davoodi1, Shahram Eslami2, Mahdi Fakhar3,4, Mohammad Aazadbakht1, Mahbobeh Montazeri2,5, Elnaz Khoshvishkaie6, Masoud Keighobadi7,8. 1. Department of Pharmacognosy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. 2. Toxoplasmosis Research Center, Communicable Diseases Institute, Iranian National Registry Center for Lophomoniasis and Toxoplasmosis, School of Medicine, Mazandaran University of Medical Sciences, Farah Abad, 48471-91971, Sari, Iran. 3. Toxoplasmosis Research Center, Communicable Diseases Institute, Iranian National Registry Center for Lophomoniasis and Toxoplasmosis, School of Medicine, Mazandaran University of Medical Sciences, Farah Abad, 48471-91971, Sari, Iran. mahdif53@yahoo.com. 4. Toxoplasmosis Research Center, Communicable Diseases Institute, Iranian National Registry Center for Hydatid Cyst, Mazandaran Branch, Mazandaran University of Medical Sciences, Sari, Iran. mahdif53@yahoo.com. 5. Toxoplasmosis Research Center, Communicable Diseases Institute, Iranian National Registry Center for Hydatid Cyst, Mazandaran Branch, Mazandaran University of Medical Sciences, Sari, Iran. 6. Pharmaceutical Cares Department, Ayatollah Khamenei Hospital, Mazandaran University of Medical Sciences, Abbas Abad, Iran. 7. Toxoplasmosis Research Center, Communicable Diseases Institute, Iranian National Registry Center for Lophomoniasis and Toxoplasmosis, School of Medicine, Mazandaran University of Medical Sciences, Farah Abad, 48471-91971, Sari, Iran. keighobadi216@yahoo.com. 8. Toxoplasmosis Research Center, Communicable Diseases Institute, Iranian National Registry Center for Hydatid Cyst, Mazandaran Branch, Mazandaran University of Medical Sciences, Sari, Iran. keighobadi216@yahoo.com.
Abstract
PURPOSE: Leishmaniasis is a major public health problem worldwide in many parts of the world. Current anti-leishmanial drugs have only limited clinical efficacy. Aurothiomalate derivatives are useful for treating rheumatoid arthritis, but have emerged as a promising therapeutic candidate for leishmaniasis. This paper gives a review of the literature about the usefulness of aurothiomalate derivatives against leishmaniasis. METHODS: In this study, we reviewed the proposed mechanisms of action of aurothiomalate and related compounds on the metabolism of L. major and collected data by searching relevant articles. RESULTS: Aurothiomalate-based drugs could be effective against leishmaniasis through two direct and indirect mechanisms: first, cytotoxic effects on parasites via thiomalate's false substrate role in the citric acid cycle against malate; and second, immunosuppressive and anti-inflammatory effects of aurothiomalate derivatives with prostaglandin production inhibitory effects. CONCLUSIONS: The current study documented that aurothiomalate-based drugs could be effective against leishmaniasis through two direct and indirect mechanisms of action. Gold thiomalate as a promising hit should be evaluated against L. major in vitro and in vivo conditions in the future.
PURPOSE: Leishmaniasis is a major public health problem worldwide in many parts of the world. Current anti-leishmanial drugs have only limited clinical efficacy. Aurothiomalate derivatives are useful for treating rheumatoid arthritis, but have emerged as a promising therapeutic candidate for leishmaniasis. This paper gives a review of the literature about the usefulness of aurothiomalate derivatives against leishmaniasis. METHODS: In this study, we reviewed the proposed mechanisms of action of aurothiomalate and related compounds on the metabolism of L. major and collected data by searching relevant articles. RESULTS: Aurothiomalate-based drugs could be effective against leishmaniasis through two direct and indirect mechanisms: first, cytotoxic effects on parasites via thiomalate's false substrate role in the citric acid cycle against malate; and second, immunosuppressive and anti-inflammatory effects of aurothiomalate derivatives with prostaglandin production inhibitory effects. CONCLUSIONS: The current study documented that aurothiomalate-based drugs could be effective against leishmaniasis through two direct and indirect mechanisms of action. Gold thiomalate as a promising hit should be evaluated against L. major in vitro and in vivo conditions in the future.
Authors: Thomas Naderer; Miriam A Ellis; M Fleur Sernee; David P De Souza; Joan Curtis; Emanuela Handman; Malcolm J McConville Journal: Proc Natl Acad Sci U S A Date: 2006-03-28 Impact factor: 11.205
Authors: Ricardo A P de Pádua; Ali Martin Kia; Antonio J Costa-Filho; Shane R Wilkinson; M Cristina Nonato Journal: Int J Biol Macromol Date: 2017-03-27 Impact factor: 6.953